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 Title Page
 Copyright
 Dedication
 Acknowledgement
 Table of Contents
 List of Figures
 List of Tables
 Abstract
 Introduction
 Background
 Materials and methods
 Results and discussion
 Summary and conclusions
 Future work
 Reference
 Biographical sketch
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Title: Surface modification of intraocular lens polymers by hydrophilic graft polymerization for improved ocular implant biocompatibility
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 Material Information
Title: Surface modification of intraocular lens polymers by hydrophilic graft polymerization for improved ocular implant biocompatibility
Series Title: Surface modification of intraocular lens polymers by hydrophilic graft polymerization for improved ocular implant biocompatibility
Physical Description: Book
Creator: Yahiaoui, Ali.
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Bibliographic ID: UF00090196
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Source Institution: University of Florida
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Table of Contents
    Title Page
        Page i
    Copyright
        Page ii
    Dedication
        Page iii
    Acknowledgement
        Page iv
    Table of Contents
        Page v
        Page vi
    List of Figures
        Page vii
        Page viii
        Page ix
        Page x
        Page xi
    List of Tables
        Page xii
        Page xiii
        Page xiv
    Abstract
        Page xv
        Page xvi
        Page xvii
    Introduction
        Page 1
        Page 2
        Page 3
        Page 4
        Page 5
        Page 6
    Background
        Page 7
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    Materials and methods
        Page 49
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    Results and discussion
        Page 71
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    Summary and conclusions
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    Future work
        Page 221
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    Reference
        Page 223
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    Biographical sketch
        Page 235
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    Copyright
        Copyright
Full Text

















SURFACE MODIFICATION OF INTRAOCULAR LENS POLYMERS BY
HYDROPHILIC GRAFT POLYMERIZATION FOR
IMPROVED OCULAR IMPLANT BIOCOMPATIBILITY
















By

ALI YAHIAOUI


A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL
OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT
OF THE REQUIREMENTS FOR THE DEGREE OF
DOCTOR OF PHILOSOPHY



UNIVERSITY OF FLORIDA


1990



































Copyright 1990

by

Ali Yahiaoui































For Amel...

















ACKNOWLEDGEMENTS


I would like to express my deep gratitude and appreciation to my

research director, Professor Eugene P. Goldberg, for his guidance,

encouragement, deep understanding, generous support and best of all his

patience to make my graduate work productive and very enjoyable.

My sincere thanks and appreciation also go out to the members of my

supervisory committee: Dr. Batich for introducing me to the fascinating

area of surface science and for showing me some of the finer aspects of

surface analytical techniques, Dr. Butler for his teaching and help in

times of frustration, Dr. Clark and Dr. Bates for their valuable time

and teaching.

Many thanks must go to all my colleagues, for their friendship and

cooperation.

I would also like to thank my parents, my brother and my sisters who

always encouraged me. Most of all I am grateful to my wife and my

children for their patience and support during those years.





















TABLE OF CONTENTS


Page

ACKNOWLEDGEMENTS .........................................................iv


LIST OF FIGURES..... ....................................................vii


LIST OF TABLES..... .....................................................xii


ABSTRACT ...................................................................xv


CHAPTERS


1 INTRODUCTION ........................................................ 1


2 BACKGROUND .......................................................... 7


2.1 Cataract Surgery and Intraocular Implants .........
2.2 Intraocular Lens Materials ........................
2.3 Biopolymer Surface Properties and Related Problems
2.4 Surface Modification Techniques ...................


............. .7
........... 13
.............19
........... 26


3 MATERIALS AND METHODS ............................................... 49


3.1 Materials .........................................
3.2 Methods.............................................


. .49
. .51


4 RESULTS AND DISCUSSION ..............................................71


4.1 Hydrophilic Surface Modification of IOL Polymers by an
Improved Radiation-Induced Graft Polymerization
Method: The "Presoak Method". .............................
4.2 Hydrophilic Surface Modification of PMMA and PDMS by
Combined RF Plasma and Radiation-Induced Graft
Polymerization Techniques: The "Plasma/Gamma Method"......


...... 71



..... 187


5 SUMMARY AND CONCLUSIONS ............................................217


5.1 Hydrophilic Surface Modification of Biopolymers by the
"Presoak Method"... .......... .................................. 217
5.2 Hydrophilic Surface Modification of Biopolymers by the
"Plasma/Gamma Method"................................................ 219















6 FUTURE WORK ................. . .................................... 221

6.1 Hydrophilic Surface Modification of Biomaterials by the
"Presoak Method"............................................................ 221
6.2 Hydrophilic Surface Modification of Biomaterials by the
"Plasma/Gamma Method"................................................ 222

REFERENCES ............................................................223

BIOGRAPHICAL SKETCH ...................................................235



















LIST OF FIGURES


Figure Page

1 Schematic representation of a normal eye and an eye with
cataract ..........................................................2

2 Typical IOL designs: (a) two-piece with PP haptics,
(b) one-piece all PMMA .......................10

3 Different types of IOLs according to their mode of fixation
in the eye: (a) Iris clip, (b) Anterior chamber,
(c) Posterior chamber ............................................12

4 Chemical structures of IOL polymers ..............................14

5 Structure of the human eye .......................................24

6 Schematic diagram of the 60Co gamma source .......................54

7 Schematic drawing of the RF Plasma apparatus .....................57

8 Schematic representation of the captive air bubble
contact angle measurements:
(a) immersion chamber
(b) air bubble at the solid-water interface ......................60

9 A typical optical diagram for attenuated total reflectance
(ATR) spectroscopy ......................................... ... 62

10 Schematic view of the interaction of an X-ray photon with an
atomic orbital ..................................................62

11 Schematic drawing on the effect of sample tilt angle on depth
of XPS analysis .......................................... ......66

12 Schematic description of the iris abrasion test instrument .......69

13 Drawing of the corneal endothelium damage test instrument ........70

14 Effect of temperature on weight uptake by PMMA soaked in
40% NVP for 4 hrs ...............................................73

15 Effects of NVP concentration and time on weight uptake by
PMMA at 600C ....................................................77














16 Effect of time on weight uptake by PMMA soaked in 40% NVP
at 600C .. .......................................................80

17 FT-IR/ATR spectrum for unmodified PMMA and expansion of the
1775-1575 cm-1 region ................. ..................... .....81

18 FT-IR/ATR spectrum for NVP-soaked PMMA .........................82

19 Variation in the graft yield of radiation grafting of
NVP on PMMA with presoak temperature ...........................88

20 UV-VIS spectra for (a) PMMA, (b) NVP-soaked-PMMA,
(c) PVP-g-PMMA ................................................... 90

21 FT-IR/ATR spectrum for radiation grafting of NVP on PMMA
under no-presoak conditions ......................................93

22 FT-IR/ATR spectrum for radiation grafting of NVP on PMMA under
presoak conditions ................................................. 94

23 FT-IR/ATR spectra for PMMA and PVP-g-PMMA obtained with
various IRE crystals ............................................96

24 XPS survey and Cls spectra for unmodified PMMA ................... 99

25 XPS survey and Cls spectra for radiation grafting of NVP
on PMMA under (a) no-presoak conditions,
(b) presoak conditions .........................................101

26 Angle resolved XPS survey and Cls spectra for radiation
grafting of NVP on PMMA under presoak conditions ...............104

27 SEM photographs for (a) unmodified PMMA, (b) PVP-g-PMMA under
presoak conditions ............................................... 107

28 Optical micrographs (130X) for cross sections of
(a) unmodified PMMA, (b) PVP-g-PMMA under no-presoak conditions,
(c) PVP-g-PMMA presoaked for 1 hour, (d) PVP-g-PMMA presoaked
for 2 hours, (e) PVP-g-PMMA presoaked for 3 hours,
(f) PVP-g-PMMA presoaked for 4 hours ............................109

29 Comparison of PVP graft yields on PMMA, PP, PVDF, and PDMS
under presoak vs. no-presoak conditions .......................... 114

30 FT-IR/ATR spectrum for unmodified PP .............................116

31 FT-IR/ATR spectra for radiation grafting of NVP on PP:
(a) under no-presoak conditions, (b) under presoak conditions ...117

32 FT-IR/ATR spectrum for unmodified PDMS ...........................118


viii














33 FT-IR/ATR spectra for radiation grafting of NVP on PDMS:
(a) under no-presoak conditions, (b) under presoak conditions ...119

34 FT-IR/ATR spectrum for unmodified PVDF .........................120

35 FT-IR/ATR spectra for radiation grafting of NVP on PVDF:
(a) under no-presoak conditions, (b) under presoak conditions... 121

36 XPS spectra for PP: (a) unmodified, (b) grafted with PVP under
no-presoak conditions, (c) grafted with PVP under presoak
conditions ....................................... ...............123

37 XPS spectra for PDMS: (a) unmodified, (b) grafted with PVP under
no-presoak conditions, (c) grafted with PVP under presoak
conditions ......................................... .............126

38 XPS spectra for PVDF: (a) unmodified, (b) grafted with PVP under
no-presoak conditions, (c) grafted with PVP under presoak
conditions ..................................................... 127

39 FT-IR/ATR spectra for radiation grafting of NVP on (a) PP,
(b) PDMS, (c) PVDF. ............................................. 132

40 FT-IR/ATR spectrum for PMAA-g-PMMA ..............................140

41 XPS spectrum for PMAA-g-PMMA .................................... 140

42 FT-IR/ATR spectrum for (PMAA-co-PVP)-g-PMMA .................... 143

43 XPS spectrum for (PMAA-co-PVP)-g-PMMA ...........................143

44 FT-IT/ATR spectrum for (PSMA-co-PVP)-g-PMMA .................... 149

45 XPS spectrum for (PSMA-co-PVP)-g-PMMA .........................149

46 FT-IR/ATR spectrum for radiation grafting of KSPA on PMMA .......152

47 XPS spectrum for radiation grafting of KSPA on PMMA .............152

48 FT-IT/ATR spectrum for PAMPSA-g-PMMA ...........................155

49 XPS spectrum for PAMPSA-g-PMMA .................................155

50 FT-IR/ATR spectrum for PAM-g-PMMA ............................. 159

51 FT-IR/ATR spectrum for PDMA-g-PMMA ..............................159

52 XPS spectrum for PAM-g-PMMA .................................... 160














53 XPS spectrum for PDMA-g-PMMA...................................... 160

54 FT-IR/ATR spectrum for PEGMA-g-PMMA...............................165

55 XPS spectrum for PEGMA-g-PMMA..................................... 165

56 FT-IR/ATR spectrum for (PVP-co-PSMA-co-PAMPSA)-g-PMMA ...........169

57 XPS spectrum for (PVP-co-PSMA-co-PAMPSA)-g-PMMA ................169

58 FT-IR/ATR spectra for (a) PVP-g-PMMA,
(b) (PVP-co-Heparin)-g-PMMA............................ .........174

59 XPS spectrum for (PVP-co-Heparin)-g-PMMA ................... ....175

60 SEM micrograph of an untouched corneal endothelium.............. .178

61 SEM micrograph of a corneal endothelium after contact with an
unmodified 3 mm PMMA stub ...................................... 179

62 SEM micrograph of a corneal endothelium after contact with a
3 mm PVP-g-PMMA stub ................. ..........................179

63 Optical micrograph (5X) of an unabraded iris ...................181

64 Optical micrograph (5X) of an iris abraded with an unmodified
PMMA IOL .......................................................182

65 Optical micrograph (5X) of an iris abraded with a PVP-g-PMMA
IOL ................................... ..........................182

66 Optical micrograph (50X) for lens epithelial cell adhesion and
spreading on unmodified PMMA slab ................... .............. 185

67 Optical micrograph (50X) for lens epithelial cell adhesion and
spreading on PVP-g-PMMA slab....................... .............185

68 Ols/Cls intensity ratio vs. reaction time for plasma oxidation
of PMMA with 50 W ................................................ 192

69 Contact angles vs. reaction time for plasma oxidation of PMMA
with 50 W.......................................................193

70 XPS Cls spectra at various photoelectron take off angles for
plasma-oxidized PMMA with 50 W for 15 min........................195

71 Typical FT-IR/ATR spectrum for plasma-oxidized PMMA with
50 W for 15 min........................................... ......197














72 XPS spectra for radiation grafting of NVP on plasma-oxidized
PMMA: (a) 50 W/5 min., (b) 50 W/15 min ....................... ...200

73 Typical FT-IR/ATR spectrum for radiation grafting of NVP on
plasma-oxidized PMMA .............................................201

74 Optical micrograph (130X) for the cross section of a typical
PVP-g-PMMA by the "Plasma/Gamma Method"................ .........202

75 XPS spectra for typical plasma-oxidized PDMS
(a) 50 W/5 min., (b) 50 W/15 min .............................. ..207

76 FT-IR/ATR spectrum for a typical plasma-oxidized PDMS ...........209

77 Typical FT-IR/ATR spectrum for PVP-g-PDMS by the
"Plasma/Gamma Method" ..................................... ....... 211

78 Typical XPS spectrum for PVP-g-PDMS by the "Plasma/Gamma
Method" ......................................................... 212



















LIST OF TABLES


Table Page

1 Physical and mechanical properties of IOL polymers ...............14

2 Chemical structures of monomers and reagents used for
surface grafting .................................................50

3 Weight uptake by PMMA as a function of time and solution
composition during presoak at 600C ............................... 75

4 Main FT-IR/ATR absorption bands for PMMA..... ....................81

5 Monomer uptake for PMMA, PP, PDMS, and PVDF during presoaking
in 40% NVP at 600C for 4 hours ..................... ..............85

6 Data on monomer uptake (%Wm) as a function of temperature during
presoak and related grafting yields (%Wg) of PVP on
PMMA ........... ............................................... 89

7 Absorbance measurements by ATR for PMMA and PVP-g-PMMA using
various IRE crystals ......................... .................... 97

8 XPS and contact angle (0) data for radiation grafting of NVP
on PMMA under presoak and no-presoak conditions........... ......102

9 Angle resolved XPS data for radiation grafting of NVP on PMMA
under presoak conditions .................... .................... 105

10 Variation of monomer uptake (%Wm), graft yield (%Wg), and
graft thickness in radiation grafting of NVP on PMMA with
respect to presoak time (i.e. monomer uptake) ................ ...108

11 Data on monomer uptake and related grafting yields on
radiation grafting of NVP on PMMA, PP, PVDF, and PDMS under
presoak vs. no-presoak conditions ...............................113

12 Main FT-IR/ATR absorption bands for PP ...........................116

13 Main FT-IR/ATR absorption bands for PDMS ......................118

14 Main FT-IR/ATR absorption bands for PVDF. .......................120

15 XPS and contact angle data for PVP grafting on PDMS, PP
and PVDF.... ........ ............................................ 124


xii














16 Data on monomer uptake and related grafting yields on radiation
grafting of NVP on PP, PDMS and PVDF, following presoaking in
100% NVP/600C/4 hrs.............................. ............... 131

17 Grafting data for PMAA-g-PMMA......... ..........................138

18 Grafting data for (PMAA-co-PVP)-g-PMMA .... ......................142

19 Grafting data for PSMA-g-PMMA .........................................146

20 Grafting data for (PSMA-co-PVP)-g-PMMA, (a) with no-presoak,
(b) with presoak.............................................. ...148

21 Radiation grafting of KSPA on PMMA, (a) with no-presoak,
(b) with presoak in various conditions......................... .. 151

22 Data for radiation grafting of AMPSA on PMMA ....................154

23 Data for radiation grafting of AM and DMA on PMMA...............157

24 Solution behavior of radiation polymerized PEGMA-400 and
PEGMA-400/NVP in water................................... .......162

25 Solution behavior of radiation polymerized PEGMA-1000 and
PEGMA-1000/NVP in water................................... ......162

26 Preliminary results for gamma radiation-induced grafting of
PEGMA-1000 on PMMA ..................................... .. ......... 164

27 Effect of NVP presoaking on grafting of PEGMA-1000 on PMMA...... 164

28 Gravimetric data for (PVP-co-PSMA-co-AMPSA)-g-PMMA ............ 167

29 XPS data for (PVP-co-PSMA-co-AMPSA)-g-PMMA .....................167

30 Experimental conditions for the two-step radiation grafting
of (NVP-co-Heparin) on PMMA ....................................... 172

31 Data for radiation grafting of (NVP-co-Heparin) on PMMA .........172

32 XPS and contact angle data for (NVP-co-Heparin)-g-PMMA ..........175

33 Rabbit lens epithelial cell adhesion ............................ 186

34 Contact angle data for oxidation of PMMA by water
RF plasma at 5, 10 and 25 W ......................................188

35 Contact angle and XPS data for oxidation of PMMA by water
RF plasma at 50 W. ................................................190


xiii














36 XPS and contact angle data for radiation grafting of NVP
on PMMA and on plasma-oxidized PMMA .............................199

37 Contact angle data for water RF plasma oxidation of PDMS. .......205

38 XPS data for water plasma oxidation of PDMS at 50 W. ............206

39 XPS data for radiation grafting of NVP on plasma-oxidized PDMS ..212

40 Contact angle measurement for PVP grafted stainless steel
and glass .......................................................215



















Abstract of Dissertation Presented to the Graduate School
of the University of Florida in Partial Fulfillment of the
Requirements for the Degree of Doctor of Philosophy

SURFACE MODIFICATION OF INTRAOCULAR LENS POLYMERS BY
HYDROPHILIC GRAFT POLYMERIZATION FOR
IMPROVED OCULAR IMPLANT BIOCOMPATIBILITY

By

ALI YAHIAOUI

December 1990

Chairman: Dr. Eugene P. Goldberg
Major Department: Materials Science and Engineering


Intraocular lens (IOL) implants have become the most common human

prosthesis. More than 2,000,000 IOLs will be implanted in 1990.

However, complications still occur. Problems arise which are related to

the surface properties of the implant materials. For example,

mechanical irritation, abrasion, adhesion-induced damage of intraocular

tissues, and postoperative lens opacification result from adverse

hydrophobic interactions between the implant and the intraocular

environment.

This research was devoted to the synthesis and characterization of

new hydrophilic IOL implant surfaces prepared by surface graft

polymerization: the major objective being to reduce hydrophobic IOL

polymer-induced complications. Two novel surface modifications were

investigated using gamma radiation and radio frequency (RF) plasma graft

polymerization techniques. Surfaces were characterized using


xv














gravimetric analysis, contact angle measurements, Fourier transform

infrared by the attenuated total reflectance (FT-IR/ATR), X-ray

photoelectron spectroscopy (XPS), ultraviolet-visible spectroscopy (UV-

VIS), light microscopy and scanning electron microscopy (SEM).

First, a "Presoak Method" was developed and was a significant

improvement over conventional radiation-induced graft polymerization.

The basic feature of this technique was a presoak of the substrate in

concentrated monomer solutions, prior to gamma-irradiation in more

dilute aqueous monomer solutions. An important aspect of this method

was the finding that it was possible to simultaneously surface modify

combinations of various polymers, of interest for IOLs, in a single

procedure. The "Presoak Method" also proved valuable for radiation

grafting of a variety of ionic vinyl monomers. Synthesis of unique

hydrophilic composite surface grafts, by incorporation of bioactive

molecules within the graft, was accomplished and was an important

application of this method.

Second, the "Plasma/Gamma Method" involved a combination of

oxidative RF plasma and gamma-induced grafting techniques. The RF

plasma oxidation introduced polar groups on the substrate surface,

thereby enhancing interfacial interactions and diffusion of monomer to

the substrate surface. The unique aspect of the "Plasma/Gamma Method"

was its ability to allow surface grafting of vinyl monomers not only on

polymers, but also on metals and ceramics.

Preliminary in-vitro biomedical studies carried out with

polymethylmethacrylate (PMMA) IOLs and slabs demonstrated that














PVP-grafted PMMA by the "Presoak Method" significantly reduced the

incidence of material-related complications.


xvii


















CHAPTER 1

INTRODUCTION




The intraocular lens (IOL) is a human prosthesis which has gained

widespread acceptance. Intraocular lenses are used today to restore

vision in most cataract patients and more than 2,000,000 implants will

be performed worldwide in 1990. A cataract is an opacification of the

natural lens of the eye, which results in loss of visual acuity (Figure

1). In severe forms, cataracts can cause blindness. Typical IOL

designs are shown in Figure 2 and their characteristics are discussed in

section 2.1.

Although significant refinements in IOL manufacturing and a high

degree of sophistication in microsurgical techniques have been achieved

in recent years, complications from IOL implantation still occur. The

exhaustive experimental and clinical data available today suggest that

commercially available IOL polymers are not as mechanically, chemically

and biologically compatible with the intraocular environment as was

originally thought (1,2,3,4).

The objectives of this research were to provide a path toward

improved long-term biocompatibility for IOL implants. Emphasis was

therefore placed on the effects of interactions between the artificial

lens and the natural intraocular environment. The results of previous

research carried out in this group have led to the suggestion that

certain hydrophilic coatings on IOL materials have the potential

























optic
nerve


EYE WITH
CATARACT


Schematic representation of a normal eye and an eye with
cataract.


light






























light


Figure 1.












advantage of reducing tissue trauma and improving long-term

biocompatibility in the eye (3,5,6).

The optics of most currently used IOLs are made of poly(methyl

methacrylate) (PMMA); the haptics or loops are made of either

poly(propylene) (PP) or PMMA (Figure 2). Other materials being

investigated include poly(dimethyl siloxane) (PDMS) for the optic and

poly(vinylidine fluoride) (PVDF) for the haptics. The general most

problematic property of these polymers is their hydrophobicity. Most

IOL material-related complications are now recognized to originate from

adverse hydrophobic surface interactions at the interface between the

implant and the natural intraocular environment. These complications

include i) mechanical irritation of sensitive ocular tissues, resulting

in inflammatory reactions, ii) adhesion-induced damage to tissues such

as the corneal endothelium, which can lead to corneal edema and

decompensation, and iii) adhesion and proliferation of lens capsule

epithelial cells, causing post-operative inflammation, and lens

opacification or secondary cataracts (1,2,3,4).

Thus, the practical value of a biomaterial strongly depends on its

surface properties. Biomaterials with useful bulk properties are

readily available, but they rarely exhibit optimum surface properties.

Surface modification of biomaterials has therefore attracted

considerable attention in the biomedical engineering field, whereby the

surface properties may be tailored for specific applications without

adversely affecting bulk properties.

Of the many surface modification techniques available, surface

modification by gamma radiation-induced graft polymerization and radio













frequency (RF) plasma treatments are most promising (7). Both methods

allow surface alterations which are otherwise not obtainable by

conventional chemical reactions.

Radiation-induced graft polymerization of hydrophilic vinyl monomers

involves heterogeneous solid-liquid reactions. Such heterogeneous

reactions are usually difficult because of thermodynamic incompatibility

between a hydrophilic monomer solution and hydrophobic substrates, which

results in high interfacial energy and repulsive forces at the solid-

liquid interface. In order to overcome these limitations, various

radiation grafting conditions have been employed (7,8). They include

the use of organic swelling agents to enhance monomer penetration into

the substrate, the use of relatively high radiation doses ( 0.5 Mrad),

and the use of inhibitors (e.g. Mohr's salts) to control excessive

homopolymerization in solution. These experimental conditions, though

useful for certain industrial applications, may introduce problems for

the preparation of biomedical devices where maximum purity for

biocompatibility is required.

It was the goal of this research to investigate surface modification

of the major IOL polymers under conditions which would avoid the use of

potentially toxic organic solvents, inhibitors, and high radiation

doses, and yet produce high graft yields. The two grafting methods

investigated were (i) a modified simultaneous radiation technique,

involving a monomer presoak prior to gamma-irradiation with a relatively

low dose ( 0.15 Mrad), and (ii) a combination of RF plasma activation

or oxidation of the substrate followed by gamma-irradiation of the

activated substrate in the presence of an aqueous solution of monomer.








5




These two methods are referred to as the "Presoak Method" and the

"Plasma/Gamma Method," respectively.

The "Presoak Method" utilizes conditions for controlled diffusion of

monomer into the substrate so that a higher monomer concentration is

present close to the active sites during the irradiation step. This

method was investigated in detail for radiation grafting of N-vinyl

pyrrolidone (NVP) on PMMA, and on PP, PDMS and PVDF as well. Perhaps

one of the most important aspects of the "Presoak Method" is its utility

for simultaneous surface modification of polymer combinations used as

lens/haptic pairs in ocular implants or other devices. Thus, surface

grafting of an assembled IOL made of PMMA optics and PP or PVDF haptics

can be accomplished with hydrophilic polymers under the same conditions

to achieve good hydrophilic surface grafts on both optics and haptics.

In addition, it has been found that the "Presoak Method" is particularly

useful to graft other vinyl monomers and comonomers of different

functionalities and ionicities, which are normally resistant to surface

grafting by the simple conventional radiation grafting techniques.

Incorporation of biologically active molecules in the hydrogel

grafts is another new area which has been investigated in this study.

Immobilization of molecules, such as heparin, albumin, enzymes, and

drugs, can impart unusual properties to the graft surfaces. In

particular, the incorporation of heparin within the PVP graft matrix was

investigated in some detail because of the potential for improved

heparinized surfaces which could exhibit useful antiinflammatory and

nonthrombogenic properties.












The "Plasma/Gamma Method," on the other hand, is a unique method

which can increase interactions between monomer solutions and the

substrates. The rationale behind this approach rests on two general

criteria. First, polarization of the substrate surface by plasma

oxidation could lower the interfacial energy and thus provide stronger

interaction and diffusion of monomer towards the substrate surface.

Second, there is a high probability of peroxide group formation which

would be easily cleaved by radiolysis to produce surface radicals which

are able to initiate the graft polymerization process. This method was

applied to graft polymerize NVP on polymers such as PMMA and PDMS, and

other materials including metals and ceramics. The surface grafting of

polymers to metal or ceramic surfaces afforded by the "Plasma/Gamma

Method" represents a unique and potentially very important new approach

to the surface modification of these materials.

Characterization of the grafted substrates was carried out by a

variety of techniques including FT-IR/ATR, XPS, SEM, UV-VIS, optical

microscopy, gravimetric analysis, and contact angle measurements.

Biocompatibility was evaluated by in-vitro studies including (i)

damage to the corneal endothelium by a static touch test (cf. section

4.5.1), (b) damage to the iris by a dynamic abrasion test (cf. section

4.5.2), and (c) adhesion and spreading of lens epithelial cells (cf.

section 4.5.3). These in-vitro tests were carried on PVP-g-PMMA IOLs

and slabs, and on unmodified similar PMMA samples for comparison. The

results of these in-vitro studies indicate that very hydrophilic surface

grafts, i.e. PVP-g-PMMA, exhibit significant potential advantages for

intraocular implants and other medical devices.


















CHAPTER 2
BACKGROUND


2.1 Cataract Surgery and Intraocular Implants

A cataract is an opacification of the normally transparent natural

lens of the eye. This opacification prevents light from passing through

the lens to the back of the eye or retina, as shown in Figure 1. Most

cataracts are believed to result from chemical compositional changes of

the natural crystalline lens caused by the normal processes of aging

(9), but congenital cataracts in children are also commonly diagnosed

(10). Common symptoms associated with cataracts are blurred or fuzzy

vision, sensitivity to light and glare, loss of depth perception, loss

of night vision, and ultimately blindness. Quoting the most recent

estimates from the World Health Organization, Minassian (11) and Roper-

Hall (12) reported that cataracts are a major cause of blindness

affecting about 20 million people worldwide. This number is continually

growing as the world population continues to expand and age.

No known prevention or drug therapy for cataracts is currently

available. When the patient suffers sufficient loss of sight, surgical

extraction of the diseased natural lens is the only effective way to

restore vision. Since the natural lens is a major focusing element of

the patient's visual system, it must be replaced. Prosthetic devices

available as substitutes for the extracted cataractous natural lens are

spectacle glasses, contact lenses, and intraocular lenses (IOLs).











Spectacle glasses are safe, simple, and relatively inexpensive;

however, the resulting quality of vision is often poor (13). Common

problems associated with spectacles are excessive magnification (=25%),

loss of peripheral visual field, distortion, spherical aberrations and

false spatial localization of objects (14). All of these problems make

spectacle correction less than satisfactory.

Contact lenses offer appreciable advantages over spectacle glasses

as magnification is reduced to =8%, and no appreciable spherical

aberrations are induced. Contact lenses, however, also have their

disadvantages. They can lead to corneal neovascularization, development

of corneal abscesses, edema, and other pathological complications (15).

Environmental factors such as dust and chemical pollution may make these

complications worse. In addition, a lack of proper lens hygiene may

lead to corneal infections and even loss of the eye (14,16).

Furthermore, contact lenses are not easily worn by people of the age

group in which cataract usually develops because of poor manual

dexterity (13).

On the other hand, IOLs minimize all the aforementioned

difficulties. Magnification averages only 2%, and no spherical

aberrations are induced. The natural lens is replaced with an

artificial one of the same power which may be put within the membranous

capsule from which the original cataract was removed. This represents

the nearest "physiological replacement" of the crystalline lens, and is

presently the best alternative to restore vision to normal.

Fechner and Fechner reported that the idea of an artificial lens

implant had been conceived in the mid-18th century (17). In 1765 an

Italian oculist, named Tadini, was first to propose the use of an













artificial glass lens prosthesis as recorded in Casanova's memoirs (17).

The first attempt for artificial lens implantation, though unsuccessful,

was performed by Casaamata in Dresden, Germany, in 1797 (17). The

history of modern intraocular lens implantation began after the Second

World War when many British veteran pilots were observed to have

polymethylmethacrylate (PMMA) fragments from shattered aircraft canopies

in their eyes with almost no inflammatory reaction (18). This prompted

the idea of using PMMA as a suitable material for the replacement of the

natural lens. In 1949, Dr.Harold Ridley in England pioneered the first

modern-age posterior chamber PMMA lens implantation in a human following

cataract surgery. This laid the ground of a new era in medical

technology. Many other ophthalmic surgeons followed Ridley's idea and a

multitude of lens designs and materials has been investigated over the

years.

An IOL consists of an optic and two haptics or fixation devices

(Figure 2). Polymethylmethacrylate is the material used by all lens

manufacturers for the optics, while the haptics can be made of the same

material or PP. Other materials currently being investigated include

PDMS and hydrogels such as polyhydroxyethylmethacrylate (PHEMA) for the

lens optics, and polyvinylidinefluoride (PVDF) for the haptics. The

different types of IOLs are usually classified according to their method

of fixation in the eye. These include the posterior chamber, the iris

clip, and the anterior chamber lens implants, as shown in Figure 3. At

present, and after four decades of evaluation, the posterior chamber-IOL

(PC-IOL) implanted in the capsular bag or ciliary sulcus is the most






























O


Figure 2. Typical IOL designs:
(a) two-piece with PP haptics, (b) one-piece all PMMA


alL
O













commonly used lens, because of its ease of maneuverability, good visual

results, and significantly low rate of complications (19).

Apple et al. have extensively reviewed all aspects of IOL

developments and related problems for the past four decades (1,20).

Although IOL implantation has provoked much controversy and debate, it

has at the same time achieved a remarkable level of success and

sophistication.

From a technical standpoint, significant refinements have been made

in lens design, finishing, manufacturing techniques, quality control,

and advanced microsurgical techniques. Today many authors believe that

IOL implantation following cataract extraction is among the safest

commonly performed major operations in modern surgery (21,22). Over 2

million IOL implants are projected for 1990 worldwide, with 1.5 million

in the U.S. alone (21).

From a clinical standpoint, however, important interfacial problems

involving the IOL material still persist, which render cataract surgery

and IOL implantation less than perfect. In recent years, an increasing

number of clinical reports have demonstrated that the best commercially

available IOL polymers are not as mechanically, chemically, and

biologically compatible with the eye environment as originally thought

(23,24). The objectives of this research have been to investigate

methods to alter the surface characteristics of currently available IOLs

in order to interact more favorably with the ocular environment.






















(a)























(b)















(c)





Figure 3. Different types of IOLs according to their mode of fixation
in the eye: (a) Iris clip
(b) Anterior chamber
(c) Posterior chamber













2.2 Intraocular Lens Materials

The polymers most used or currently suggested for use in IOL

applications are PMMA, PP, PVDF, PDMS, and PHEMA whose structures and

physical properties are shown in Figure 4 and Table 1, respectively.

These polymers span a broad range of properties: from rigid to

elastomeric, and from hydrophobic to hydrophilic. In this section, the

benefits and limitations of each polymer will be discussed according to

their application either as optics or haptics.

2.2.1 IOL Optics

Polymethylmethacrylate is a thermoplastic polymer that has been used

in various applications since the 1940s because of its good combination

of physical and mechanical properties, and ease of processing. It has

been extensively used as a biomaterial in several medical specialties

with good tissue tolerance (25). In ophthalmic applications in

particular, PMMA has shown relatively good ocular tolerance,

biostability and biological inertness since its introduction by Ridley

in 1949 (26).

Commercially produced PMMA is a light weight completely amorphous

polymer. It has exceptional optical clarity (over 90% transmission of

the incident light), and relatively good weatherability. At room

temperature, PMMA has good mechanical properties, and excellent

dimensional stability. This polymer can be easily machined and polished

due to its high strength and impact resistance (27).

Polymethylmethacrylate is familiar to the general public under such

trade names as Plexiglas (Rohm and Haas), Lucite (duPont), Perspex

(ICI), and UVEX (Pharmacia).















CH3
I
- (CH2--C-) n-


COO-CH2-CH2-OH


PHEMA


CH3


-(Si--O-)n-
I
CH3


PDMS


-(CH2--CF2-)n

PVDF


Figure 4. Chemical structures of IOL polymers.


Table 1. Physical


Property

Density(g/cc)

Refractive Index

Tg (C)

Tensile
strength (Kpsi)


Ultimate
elongation(%)


Modulus (Kpsi)

Contact angle (0)

Equil.water
content(%)

(source: ref.27)


and mechanical properties of IOL polymers


PMMA

1.18

1.49

105


8-10


PP

0.91

1.49

-19



4-6


PVDF

1.75




-39


PDMS

1.14

1.43

-123


PHEMA

1.16

1.43


5.5-7.9 0.85-1.2 0.07


2.5-5.4 50-100 25-500 350-600


14.5

70



1.2


160-230

90


<0.05


1.16

110



<0.04


0.725

20



38


CH3
I
- (CH2--C-)n-
I
COOCH3


PMMA


CH3
I
- (CH2--CH-)n-


PP


--~-


--













Although most IOL optics used today are made of PMMA, there are

limitations associated with its rigidity, hydrophobicity, and

sterilizability. First, PMMA.is a hard, rigid material which requires a

relatively large incision (6-10 mm) for insertion of the lens. This can

delay postoperative visual rehabilitation and cause wound-induced

astigmatism (28). Second, a chronic low grade postoperative

inflammation is commonly observed in patients and is associated with

surgical trauma, irritation of sensitive ocular tissues, and residual

lens material (23). Third, PMMA is not physically stable at high

temperatures (Tg = 1050C), and therefore cannot be autoclaved. It must

therefore undergo dry-pack sterilization using toxic ethylene oxide

(29). Because of these limitations, the trend in recent years toward

softer, flexible, elastic and autoclavable IOLs has bolstered interest

in PDMS and PHEMA as IOL polymers (25). An inherent advantage of soft

and flexible IOLs, is that they might be folded and inserted in the eye

through a small incision (< 4 mm), and then be allowed to unfold

intraocularly to their normal shape. This can lead to a faster recovery

for the patient and may reduce the potential of wound-induced

astigmatism. Both PDMS and PHEMA IOLs can be sterilized by autoclaving

which is more convenient and safer than ethylene oxide.

Polydimethylsiloxane has been widely used in medicine for over 30

years, principally for contact lenses, scleral buckles, glaucoma shunts,

prosthetic heart valves, hydrocephalic shunts, nasolacrymal intubation

tubes, breast augmentation, and other plastic and reconstructive

surgical applications (30). The chemical structure of PDMS is shown in

Figure 3. The characteristic features of such siloxanes are the













-Si-O-Si- bonds which form their backbone chain. Not only are such

bonds relatively resistant to breakage in biochemical environments, but

their exceptionally high mobility and flexibility impart unusually high

permeability to oxygen, water, ions, and small molecules (29).

However, there have been some concerns about the biological

inertness of PDMS in the eye. Polydimethylsiloxane lenses have been

shown to cause irritation, adhesion and damage to living tissues, and to

exhibit a rapid onset of fibrosis and lens opacification (28,31).

Strong absorption of hydrophobic biocomponents such as lipids may also

be associated with changes in transparency and refractive power of

silicone lens optics (32). Reports on the immunogenicity of PDMS are

contradictory. Mondino et al. were unable to demonstrate significant

complement activation (33), but Gobel et al. concluded that "siloxanes"

can activate the alternate complement pathway, resulting in an

inflammatory reaction (34).

Polyhydroxyethylmethacrylate, on the other hand, is a hydrogel which

belongs to a class of synthetic polymeric materials that swell in water

when hydrated and become soft and flexible. Hydrogels are attractive

biomaterials because they mimic very closely the physical properties of

living tissues. Over the past 20 years, hydrogels have been

successfully applied to a variety of biomedical applications such as

contact lenses and controlled release drug delivery systems (35).

The most significant advantage of hydrogels over siloxanes and PMMA

is their high hydrophilicity (contact angle =200) and water content (240

wt%). The feasibility of using PHEMA hydrogels as IOL materials has been

considered since the early 1970's (25). In-vitro and in-vivo studies












conducted in this laboratory (36) and elsewhere (37) have shown that

hydrated hydrogel IOLs are biocompatible with ocular tissues and may

reduce damage to endothelial cells on contact with the cornea. Clinical

trials with hydrogel IOLs have been attempted and the results indicate

good biostability and significantly reduced trauma to ocular tissues

(38,39).

Hydrogels have not, however, been fully developed as suitable

substitutes for PMMA. Their major disadvantages include poor mechanical

strength which may result in tearing during insertion and manipulation,

and a high flexibility which may increase the potential for distortion

and dislocation (37,40).

In order to overcome the inherent mechanical weakness of hydrogels,

special grafting techniques such as gamma radiation and RF plasma have

been developed whereby a thin layer of hydrogel can be covalently

attached to a variety of polymeric substrates (41). The various aspects

of these techniques will be addressed in section 2.4.




2.2.2 IOL Haptics

Polypropylene is currently the most widely used polymer as a haptic

material for IOLS. The interesting characteristics of PP are its

excellent bulk mechanical properties such as flex fatigue, strength,

elasticity, and flexibility, which make it useful in a number of other

medical uses such as sutures for heart and vascular surgery. Although

PP shows relatively good biocompatibility in other parts of the body,

its ocular use has raised some concerns because of the susceptibility of

this material to ultra-violet (UV) degradation. From in-vitro stability

studies, Apple et al. have observed superficial changes on PP lens













haptics as a function of time (20). Clayman has suggested that these

changes are a result of oxidative biodegradation (42). Other

researchers, however, have shown convincing evidence that alterations of

PP haptics are probably due to cracking of a biological protein coating

deposited on the PP surface and are artifacts of drying or SEM

processing (43). Most recent studies have shown that the changes seen

on PP haptics are superficial, involving only the outer 1-2% of the

haptics (1), but whether or not this is clinically significant has yet

to be demonstrated. Other concerns have been expressed that PP may

activate the alternate complement pathway, allowing the potentiation of

inflammatory mechanisms (34).

Polymethylmethacrylate is the other major haptic material. Although

PMMA is biologically more inert than PP (24), it is much less flexible

and thus is more susceptible to stress cracking and embrittlement. The

possible fracture of PMMA haptics in the eye has been a major concern

since the early development of the one-piece all-PMMA IOL; in fact, such

failures have been reported in the literature (44,45). However, this

concern seems now to be offset by recent advanced lens designs which

allow for control of the degree of flexibility and compressibility

without compromising the long-term mechanical stability of PMMA haptics

(1). There is some evidence suggesting that the one-piece all-PMMA

lenses are more advantageous than lenses with PP haptics because of the

simplicity of design, smoother surface finish, and lower susceptibility

to structural defects such as protrusions or burrs at the tip of the

haptics, or at the lens-optic junction (2,46). In addition, it has been

suggested that one-piece all-PMMA lenses may be more stable and involve













less intraocular inflammation because of lower chemotactic activity of

PMMA (21).

Polyvinilidinefluoride (shown in Figure 3) is a relatively new

polymer currently being considered as a possible substitute for PP as a

haptic material. It was first introduced and used in Japan where

preliminary clinical data has indicated that PVDF haptics have good

biostability, as reported independently by Yamanaka et al. (47) and

Shimizu (48). Polyvinilidinefluoride is hydrophobic and is considered a

promising biopolymer due to its unique combination of thermo-chemical

stability, resistance to UV degradation (49), abrasion resistance,

dimensional stability, and good mechanical properties (50).




2.3 Biopolvmer Surface Properties and Related Problems

2.3.1 Interfacial Phenomena and Biopolvmers

Adverse interfacial reactions occurring between foreign surfaces and

biological environments are the preeminent factors restricting the use

of synthetic materials. Adhesion of biological components play a major

role in determining the biocompatibility of implant devices. One focus

of the biomedical engineering field has been to elucidate those

biomaterials parameters which would either favor or impede bioadhesion

depending on the requirements of the implant (51).

Interfacial phenomena involving prosthetic implants have been

described empirically over many years and in a variety of situations.

In particular, much attention has focused on blood compatibility and

tissue acceptance. The observations of many research groups have

resulted in the formulation of various hypotheses, based upon general













physicochemical considerations, to explain interfacial properties of

these materials.

The most well known of these theories are the "moderate surface

energy" model of Baier (52), the "minimum interfacial energy" hypothesis

originally proposed by Andrade (53), and modifications of these ideas,

e.g. by Ruckenstein and Gourisankar (54), and by Ratner et al. (55).

Many of these theories have been very useful in certain simple and

short-term applications. Now, however, as the demand and constraints

for prosthetic implants are greater, these theories are of limited value

in predicting the long-term biological response or explaining the

mechanisms involved at a tissue-material interface.

Bioadhesion is a phenomenon regulated by a complex set of molecular

factors involving the physicochemical properties of a material's surface

and the interfacing physiological environment. The surface parameters

that have been shown to influence the biological response include

surface energy, chemical functional groups, ionicity, ultrastructure

morphology, compliance, molecular motions, water content and electrical

conductivity (56). However, fundamental studies aimed at elucidating

the relative importance of these parameters have been difficult and

inconclusive because of the inherent chemical complexity, structural

heterogeneity and dynamic aspects of biological systems (53,57).

Nevertheless, current understanding based on the exhaustive

experimental data available suggests that the events occurring at an

implant-tissue interface may be divided into two well-recognized

processes: i) molecular interactions such as adsorption of proteins

which occur immediately in all medical implant devices when contact is












made with biological media; ii) cellular interactions such as platelet

adhesion, lens epithelial cell adhesion and proliferation, and fibrosis

(58)

Studies by Absolom et al. on the thermodynamics of protein

adsorption to polymeric surfaces of different surface energies suggest

that strong and irreversible protein adsorption is usually observed with

hydrophobic surfaces, whereas hydrophilic surfaces readily desorb

proteins (59). Andrade had also invoked the importance of hydrophobic

interactions in aqueous physiological media which tend to facilitate

protein adsorption, and cellular adhesion and growth (60).

The influence of protein adsorption on cell adhesion and spreading

has been well documented (61). The presence of highly specific cell

attachment sites on certain protein molecules, and their interaction

with cell membrane receptor sites is believed to be the major mechanism

underlying cell behavior (adherence, growth, spreading, morphology,

motility, and metabolism) on foreign surfaces (61).

The literature on bioadhesion phenomena and related biocompatibility

is very extensive. No attempt will be made here to review the subject

in detail. Comprehensive reviews have been written previously by Osborn

(6) and Hofmeister (62), both from this research group, as well as by

others (53,59,60). What follows is therefore a description of some of

the more pertinent problems of IOL surface properties, how these

properties are believed to affect long-term performance of IOL implants,

and, in the context of the research, consideration of the relevance of

permanent protective hydrophilic coatings.













2.3.2 IOL Surface Interactions and Related Problems

A growing number of clinical reports suggests that complications

such as abrasion of ocular tissues, adhesion-induced damage to the

corneal endothelium, and postoperative lens capsule opacification are

commonly diagnosed. These complications are induced by adverse

interfacial phenomena directly related to the surface characteristics of

the implant material. Although these complications may vary in nature

and extent, they all appear to originate from hydrophobic tissue

interactions.

2.3.2.1 Mechanical abrasion of ocular tissues

The chronic mechanical abrasion caused by frequent rubbing or

chafing of IOL haptics against fragile tissues such as the iris (Figure

5) is one critical issue with PC-IOLs. Iris chafing has been implicated

as the cause of transillumination window defects and pigment dispersion

glaucoma in a number of recent clinical specular microscopy studies of

lens implant patients (2,20). Pain for the patient, antigenic

initiation of inflammatory process, growth of abnormal tissue, and other

complications may be observed.

Animal studies carried out in this laboratory indicate that

mechanical abrasion and irritation by hydrophobic surface interactions

can cause tissue trauma in all types of surgery (e.g. thoracic,

abdominal, vascular, ocular, etc.) and poses a significant, but not yet

appreciated, problem for instrument or device materials in surgery

(3,4,5). These studies also indicate that temporary or permanent

hydrophilic coatings reduce the interfacial free energy between the

prosthetic device and the tissue as well as lubricate the surface of the













device. This lowers frictional shearing forces, and can thus

significantly reduce the incidence of tissue abrasion and damage

(63,64).

2.3.2.2 Corneal endothelium damage

Corneal endothelium (Figure 5) serves an essential function in

maintaining fluid balance within the cornea. It was first shown in

this laboratory, that contact between hydrophobic PMMA IOLs and the

corneal endothelium results in biophysical adhesion and with stripping

away of endothelial cells on separation of surfaces (4,5).

Adult human endothelium does not regenerate; it normally heals by

spreading of the remaining viable cells (65). The total density of

endothelial cells is thereby reduced; this can lead to corneal edema and

decompensation which may cause pain and blindness.

Although the incidence of endothelium damage has been significantly

reduced with the increased use of PC-IOLs and the use of tissue-

protective viscoelastic polymeric solutions such as sodium hyaluronate

(HA), there still exists a possibility of accidental contact between the

IOL and the corneal endothelium during surgery (66). In addition, HA is

expensive and can lead to transient glaucoma complications. The use of

HA appears to be responsible for abnormal postoperative intraocular

pressure (IOP) elevations, especially in eyes with preexisting glaucoma

(67-69). Elevated IOP (128 mm Hg) is known to cause visual field loss

and optic nerve damage (70).

A potentially better alternative, investigated in this research, for

the protection of ocular tissues during and after IOL surgery is based

on polymer surface engineering, whereby a hydrophilic coating is














corneal epithelium


--- stroma


-- corneal endothelium


optic nerve


Figure 5. Structure of the human eye













permanently grafted on the IOL surface. This approach allows long-term

lubrication of the implant-tissue interface and a significant reduction

in biophysical forces of adhesion. Such surface modified IOLs would be

especially valuable for inhibiting tissue damage during the life of the

implant.

2.3.2.3 Postoperative lens ooacification

Postoperative opacification, also called secondary cataract, is a

common problem associated with IOL prostheses. It is attributed to

proliferation and migration of residual lens epithelial cells

and fibroblasts onto the posterior lens capsule and the surface of the

hydrophobic PMMA implant. Lens opacification causes glare and loss of

visual acuity, and occurs in about 50% of IOL implant patients within 5

years postoperatively (1). Cellular adhesion and proliferation is a

serious problem not only with IOL implants, but is also a leading

cause for the failure of other ocular surgical procedures such as

glaucoma filtering surgery (71,72).

Currently the method of choice for the treatment of lens

opacification is by non-invasive Nd:YAG (Neodymium:Yttrium Aluminum

Garnet) laser capsulotomy (73). The opaque capsule is destroyed by

localized laser bursts, and lens epithelium growth is permanently

inhibited (74). Although this procedure is considered "safe," there are

concerns about laser-induced damage to the IOL surface (75,76), to the

endothelium (77), and to the retina (78).

The focus of the present research has therefore been to develop

methods to improve the surface properties of currently available IOLs in

order to enhance long-term biocompatibility and minimize the need for













postoperative treatments. The strategy is based on tailoring the

implant surface properties to minimize tissue abrasion and contact

adhesion damage, impede cellular growth, and thereby enhance

biocompatibility. Improved surface modified IOLs are of prime

importance not only for adult patients, but also for children who are

more prone to the complications discussed above (79).



2.4 Surface Modification Techniques

Historically, most efforts to improve IOL performance have

concentrated on changing the design. Complications, however, still

persist with the best designed IOLs. Research today therefore focuses

on improved biopolymers and surface properties. The concept of a IOL

surface modification is now of growing interest, and several methods for

surface modification of polymers are being evaluated (7).

Two major processes which have been studied for preparing surface

modified biopolymers are radiation graft polymerization and RF plasma

discharge. These two methods have a unique ability to initiate surface

chemical reactions without the need for chemical initiators or heat.




2.4.1 Gamma-Radiation

Gamma-radiation is a type of electromagnetic radiation similar to X-

rays, only differing in the manner in which they are produced. There

are various sources of gamma-rays, but the source in most widespread use

is cobalt-60 (60Co), a radioisotope produced by the nuclear activation

of cobalt-59. 60Co is advantageous because of its availability, high

energy, and a half-life of 5.3 years (8).












Unique characteristics of gamma-radiation include high penetration

power, unselective absorption by matter, and ability to activate

materials which may be unreactive under ordinary conditions (80).

gamma-radiation is thus particularly well suited for polymerization of

liquid monomers, and the generation of free radicals on the surface and

within the bulk of polymeric substrates as well (81).

The use of gamma radiation for the synthesis of biopolymers has the

potential advantages of cleanliness, simplicity and low cost, as

compared to the usual chemical techniques. Radiation initiation, for

instance, allows polymerization without chemical initiators, sensitizers

or catalysts, thus producing extremely "clean" polymers which are free

of potentially toxic residual contaminants. This is an important

consideration for medical applications where maximum biocompatibility is

critical.

2.4.2. Radiolvsis of Polymers

The effects of radiation on polymers have been extensively studied,

and numerous reports and reviews have been published (7,81-83). The

gamma-irradiation effects on polymers are generally well understood and

result in crosslinking and/or chain scission with the concomitant

formation of free radicals. However, mechanisms underlying such effects

are unclear (84).

Many electron spin resonance (ESR) studies have been carried out in

order to elucidate the exact nature of the radical species involved and

the reaction sites in the polymer chain. The ESR spectra obtained are

often complex and more difficult to interpret than those of small

molecules. This is attributed to the inherent characteristics of

polymers, the presence of secondary constituents (additives,













contaminants, etc.), and differences in the stability of the free

radical fragments (81,84).

Nevertheless, it is recognized that the predominant radiolysis

reactions in polymers are usually preceded by one or more side-chain or

functional group bond-breaking reactions not directly involving the

polymer backbone. Many such reactions are presented in the literature,

and a few are well supported by experimental evidence. A brief review

of the radiolysis of polymers and formation of free radicals pertinent

to this research is presented below.

2.4.2.1 Radical formation on PMMA

The gamma-irradiation of PMMA has been widely studied and reaction

products are mainly those of chain scission (81,85). Several mechanisms

for PMMA radiolysis have been reported. Equation 2.1 shows a mechanism

postulated by Todd, wherein a hydrogen atom is abstracted from a

secondary carbon to form the radical 1 (86), which then

disproportionate, leading to chain scission and the formation of free

radical 2 and a polymer molecule with an unsaturated chain end 3.

From ESR studies, Kirsher et al. have also given some evidence for a

direct main chain homolysis producing radical species 4 and 5, as shown

in equation 2.2 (87). This mechanism is further supported by recent

studies by Plonka and Pietrucha (88).

Ranby and Rabeck reported that a degradation mechanism (shown in

equation 2.3) for PMMA may involve the cleavage of the ester side group

with resultant formation of radical 6. Subsequent P-scission of radical

6 leads to a main chain scission, producing another terminal radical 5

and a polymer chain with an unsaturated end 7 (89).
























CH3 CH3 CH3 CH3
i I I
--CH2-C-CH-C-- > -CH + CCH-C---
I I 2 I
COOCH3 COOCH3 COOCH3 COOCH3
1 2 3


C3 CH3
- c-CH2-C--CH2-
COOCH3 COOCH3


CH3 CH-3 CH3
> --C-CH2- C + CH2- C--
CI I OOC
COOCH3 COOCH3 COOCH3
4 5


CH3 CH3 CH3
I I Cl-I
-- C-CH2-C-CH2-- > 5 + --C=CH2

COOCH3


(2.1)


(2.2)


(2.3)













2.4.2.2 Radical formation in PP

Electron spin resonance studies on gamma-irradiated PP in vacuum

have shown that initial radical formation occurs mainly at the tertiary

carbon, and to a lesser extent at the primary and secondary carbons as

shown in equation 2.4 (90,91). These initial alkyl radicals may undergo

further reactions such as formation of internal unsaturation. This

occurs by removal of a hydrogen adjacent to an existing double bond

leading to resonance stabilized allyl radicals as shown in equation 2.5

(91). Allylic radicals formed by other mechanisms and other types of

internal unsaturation are also possible (91).

2.4.2.3 Radical formation in PDMS

Radical formation in PDMS was investigated by Charlesby and Omerad

about 30 years ago (92). Their findings indicated that the Si-C and C-H

bonds are more susceptible to radiolysis than Si-O bonds (equation 2.6).

These results agree with more recent studies, and correlate well with

the relative intrinsic strength of the chemical bonds (93).

2.4.2.4 Radical formation in PVDF

Polyvinylidinefluoride is a relatively new polymer which has been

observed to crosslink upon gamma-irradiation (87). Although no data is

available in the literature describing its detailed radiolysis

mechanismss, it is well known that cleavage of the C-H and C-C bonds

are the most common reactions in hydrocarbon-containing polymer.

Radiolysis of C-F bonds has also been shown to occur in other

fluorocarbons, e.g. F atoms are produced from gamma-irradiation of

poly(tetrafluoroethylene) (PTFE) (94). By analogy, the possible

radiolysis products of PVDF are given in Equation 2.7.





















--CH-CH2-CH- CH2-~

CH3 CH3


gamma


rays


~ CH2-CH-CH2--
CH2
"CH2


> CH-- --CH--
SH CH3
CH3 H CH73


--CH2-- C-- CH2-

CH3


-CH-CH-CH- H-
CH3 CH3









CH3
-(Si-O-)
CH3


gamma
------> -C('

rays CH








gamma


rays
rays


-CH--CH-- --- > C CH-C--
S CH CH CH
[3 OH3 CH3 CH3


CH2

-(Si-O-)
CH3


- (i-O-)
CH3


H
gamma > --CF2-C-CF2--
--CH2-(CF2-CH2-)nCF2-

rays > --CF2-CH 2




P-H gamma
S+ 02 --> P--O ---> P-O-O-H -->

Says
p'
gamma rays

P-O-O-P


F

, --CH2--CH2--

(2.7)

SCF 2-CH2-





PO* + 'OH (2.8)


2 P-O (2.9)


(2.4)


(2.5)












(2.6)


f













To this point all the mechanisms described (Equations 2.1-2.7)

represent the initial radicals formed in various polymers when

irradiated in an oxygen-free environment. In the presence of air

however, other reactions which involve interaction between the primary

radicals and oxygen may take place. These reactions, usually lead to

formation of peroxide groups and crosslinking, as shown in equations 2.8

and 2.9, respectively (95,96). Although peroxidation is known to

enhance the oxidative degradation of most polymers, it may be

advantageous for surface grafting. It is well known that peroxide

groups decompose very easily forming free radicals which can initiate

graft polymerization of vinyl monomers.



2.4.3 Gamma Radiation-Induced Polymerization of Vinyl Monomers

About 30 years ago it was found that high energy ionizing radiation

could be successfully used for the initiation of polymerization (81,83).

Most vinyl monomers irradiated in an aqueous environment polymerize via

a free radical mechanism. Unlike initiation of polymerization by

chemical means, gamma radiation generates radicals with virtually any

kind of organic molecules; and the number of primary radicals depends

only on the instantaneous gamma radiation dose rate.

The kinetics of radiation-induced graft polymerization of vinyl

monomers onto polymeric substrates has been extensively reviewed by

Chapiro (81). He pointed out that at low dose rates (101-103 rad/min.),

"normal" kinetics are usually observed, showing that the rate of

polymerization, Rp, is proportional to the square root of the rate of












initiation (or dose rate) Ri, and to the first power of monomer

concentration, i.e.

Rp (Ri)1/2 [M] (2.10)

Chapiro indicated, however, that this relationship fails beyond a dose

rate of about 1000 rad/min, where chain termination by primary radicals

predominates. Moreover, the kinetic chain length V, defined as the

average number of monomer molecules polymerized per initiating primary

radical, has been shown to follow the same kinetic equation as for

conventional free radical polymerization. The kinetic chain length is

proportional to the monomer concentration squared and inversely

proportional to the polymerization rate or radical concentration, i.e.




v [M]2/ Rp (2.11)


2.4.4 Gamma Radiation-Induced Graft Polymerization of Vinyl Monomers
onto Polymeric Substrates


From the previous discussion, it is clear that gamma radiation is a

unique polymerization initiator and is particularly valuable in polymer

chemistry, especially in the field of biomedical polymeric materials.

The use of gamma radiation offers the possibility of synthesizing

polymers with a unique combination of bulk and surface properties;

polymers which are not possible to obtain through conventional organic

synthesis. A graft polymer is usually produced by chain transfer of the

growing radical to the substrate polymer or by direct attack of the

radiation on the polymer (81,95).

Two general techniques for surface grafting are usually employed;

pre-irradiation grafting and one-step direct or mutual grafting. The

pre-irradiation technique is a two-step process which involves













activation of the substrate by radiation in an inert atmosphere and at

low temperature to generate free radicals, or in air and at ambient

temperature to generate peroxide groups on the substrate (81,83). These

mechanisms are summarized in equations 2.1-2.9. Graft polymerization is

then usually carried out by immersing the activated substrate into an

aqueous monomer solution in an oxygen-free environment at relatively

higher temperatures (00 to 600C).

The key advantages of the preirradiation method are that graft

polymerization is restricted to the surface of the substrate and the

solution homopolymerization is very low. In addition, this method is

particularly valuable if labile biological components (e.g. enzymes,

drugs, etc.) were to be incorporated within the graft since the monomer

solution is not exposed to radiation (96).

However, the disadvantages of the preirradiation method are

numerous. First, the relatively high doses (2 5 Mrad) necessary to

generate sufficient "long-lived" radicals may result in the

deterioration of the mechanical properties of the substrate, as severe

chain scission and degradation can occur (8,81). Second, the extent of

grafting is normally low and heterogeneous, due to the inherent

structural heterogeneity of the surface and due to differences in the

stability of the radicals in the amorphous and the crystalline phases

(97). Third, from an industrial process standpoint, the preirradiation

technique is not very practical because of the low temperature and/or

inert atmosphere requirements necessary to slow down the decay of the

radicals on the substrate.













The mutual or direct irradiation technique, on the other hand, is a

process involving exposure of the polymeric material to radiation in the

presence of monomer, all in one single step. The surface graft

polymerization then occurs along with solution homopolymerization. A

major advantage of this method is its high efficiency as the radicals

are utilized to initiate graft polymerization as fast as they are

produced. However, the major disadvantage is the fact that gelation or

a Trommsdorff effect takes place very quickly, and reduces diffusion of

monomer to the polymer surface (81,83). Because graft polymerization at

room temperature is a diffusion-controlled process, the graft efficiency

generally plateaus very quickly, regardless of further irradiation

(81,95).

From a practical standpoint, gelation of the homopolymer makes

sample handling (removal from the polymerized medium) and washing very

difficult. Surface uniformity may be poor and delicate devices such as

IOLs may also not withstand this process without adverse effects to the

quality and the physical integrity of the lens.

The use of inhibitors such as Mohr's salt (ammonium ferrous sulfate)

to slow the onset of solution gelation have been reported (98).

Although radical inhibitors have shown some success in industrial

applications, such as preparation of hydrophilic surface modified

membranes for mass separation processes, they are not suitable for

preparation of biomedical devices where maximum purity for

biocompatibility is required.

The diffusion effects and swelling of the substrate by the monomer

have been shown to play a very important role in the enhancement of













graft polymerization. To facilitate such diffusion, swelling agents

have been used to open the physical structure of the host polymer. This

procedure was first studied by Heinglein et al. in 1958 (99). They

examined the gamma-induced graft polymerization of NVP onto PMMA using

methanol as a swelling agent. While this process yielded a graft, it

also resulted in severe distortion of the PMMA, along with changes in

physical properties (optical clarity) and mechanical properties crazingg

and cracking caused by methanol).

The emphasis of this research has been the investigation of a

modified one-step irradiation technique applicable for hydrophilic

surface modification of various hydrophobic biopolymers. This method is

based on a monomer/water/substrate system which can yield highly

efficient grafting at very low gamma dose (0.15 Mrad) and where neither

organic swelling agents nor inhibitor for solution homopolymerization

are required. Typically the substrate is presoaked at high

concentration of the grafting monomer, unless otherwise indicated, for a

period of time and at a temperature sufficient to facilitate diffusion

of the monomer into the substrate. Then the substrate is transferred to

a lower monomer concentration immediately prior to gamma-irradiation

(100). This method is termed a "Presoak Method" and has been found to

promote increased partitioning of the monomer in the substrate region.

As a result, an interpenetrating network (IPN) type of graft embedded in

the subsurface of the substrate is obtained at low radiation doses

(S 0.15 Mrad) and low monomer concentrations (e.g. 510 Wt.% NVP). The

"Presoak Method" has been found to yield more homogeneous and more

stable surface grafts than those obtained without presoaking.












The easily controlled presoak parameters ([M], time, and TOC) offer

the possibility of synthesizing permanent grafts of virtually any

thickness, ranging from 0.1 to 300 pm, without significant alteration of

the bulk and physical properties of the substrate polymer. A patent

application for this process has been filed (100).




2.4.5 Glow Discharge RF Plasma

Over the past two decades RF plasma initiation has emerged as a

powerful technique for surface modification of polymeric materials.

Chemical reactions that occur under plasma conditions are generally very

complex, but are useful when special excited states of molecules are

desired to afford unique chemistries which cannot be obtained by

conventional chemical reactions (101).

A glow discharge RF plasma results from free electrons that are

accelerated, at reduced pressure, in the high energy electrical field

created by an inductively coupled RF current. As they accrue sufficient

kinetic energy these electrons collide with gas molecules present in the

reactor, causing their excitation to higher energy states, with the

concomitant production of ion radicals, ions, excited atoms and

molecules, free radicals, electrons, and electromagnetic radiation

(102). Typical species generated in an argon and oxygen plasmas, for

example, are shown in equations 2.12 and 2.13, respectively.

+
Ar > hV + Ar + Ar + e (2.12)

+ +
02 > hV + 02 + O* + 02 + O + e (2.13)

The effects of RF plasmas on polymer surfaces generally involves

free radical mechanisms. In the initiation step, polymer radicals are

formed by several different processes:















By UV radiation


hV
R-H >



By excited noble gas

r>
Ar
R-H >

*>


R* -+ H*


atoms


R-H

R*

R1


By hydrogen radicals



R-H -H>-

>


(2.14)


+ Ar

+ H*

+ R2*


(2.15)


R* + H2


(2.16)


+ R20'


By oxygen radicals


O* F> R*
R-H >

L> R1*


+ H* + 02


(2.17)


+ R20*


These polymer radicals then undergo chain scission, radical transfer,

disproportionations, and recombination. These reactions give rise to a

combination of degradation, ablation, oxidation, crosslinking, and

production of unsaturation in the top surface layers (103,104).

An important and unique aspect of RF plasma treatment is the use of

gases that directly introduce functionalities on the topmost layers of

the polymer surface. This may be carried out by using plasma that

oxidize, nitrate, hydrolyze, or aminate the polymer surface (105)













Another advantage of the inherent extremely high energy of the gas

plasma is its ability to surface modify polymers which are notorious for

their resistance to other surface treatment. Moreover, the gas plasma

can be controlled to produce homogeneous and specific surface

functionalization without affecting the bulk properties of the base

polymer.

On the other hand, RF plasmas have drawbacks. Probably the most

significant is the absence of a viable theory for predicting plasma

polymer structures. This is because plasma treatments deal with complex

reactions involving a variety of reactive species, and are highly system

dependent. Finally, the stoichiometry of plasma products is often not

related in a simple manner to that of the starting reactants.


2.4.5.1 Mechanistic aspects of surface modification of polymers by glow
discharge RF plasma


The detailed mechanisms by which plasmas interact with solid

surfaces are complex and are not well understood. A wide variety of

active species are involved. The consensus, however, seems to be that

the overall effects can be interpreted in terms of two general

mechanisms; i) direct energy transfer resulting from the plasma active

species interacting with the substrate surface (i.e. sputtering of the

surface), and ii) radiative (or nondirect) energy transfer from the

ultraviolet (UV) component of the electromagnetic radiation emitted from

the plasma (106). Clark and Dilks have shown the effectiveness towards

surface modification for each of these modes of energy transfer. Their

work indicates that excited species capable of undergoing direct energy

transfer to a surface have a relatively short mean-free path (of the













order of a few monolayers), which therefore affects only the very

surface of the sample (107). UV radiation, on the other hand, which is

strongly absorbed by most polymers, has a much longer mean-free path and

may undergo a radiative energy transfer affecting both the surface and

the subsurface of the sample to a depth up to ca. 10 pm (107).

Clark and Dilks concluded that the prevalence of either mechanism

depends on the nature of the plasma and extent of exposure of the

polymer to it (107). Further, Yasuda suggested that the presence of

water vapor or any other oxygen-containing molecules during the plasma

process, remarkably enhances the radiation effect of the plasma, thus

increasing the potential for oxidative degradation and formation of free

radicals (108).

2.4.5.2 The effect of glow discharge RF plasma on polymer surfaces

Depending on the nature of the gas molecules, Yasuda has classified

plasma reactions into two categories : i) plasma polymerization or

polymer-forming plasma, and ii) plasma treatment or non-polymer-forming

plasma (101). The various aspects of the two processes are discussed

below.

2.4.5.2.1 Plasma Dolymerization

Plasma polymerization occurs generally when the gas molecules are

organic vapors, producing polymers generally recognized as "plasma

polymers" having unique characteristics that cannot be obtained by other

chemical methods (101). Virtually any organic molecule in the vapor

phase can be polymerized and conventional vinyl monomers are therefore

not required. Plasma polymerized films can therefore be prepared with

an extremely wide range of compositions and surface energies through the













choice of "monomer," and discharge reaction conditions. Kobayashi et

al. were among the first to investigate the plasma polymerization of

saturated and unsaturated hydrocarbons (108). Their findings indicate

that saturated alkanes polymerize much slower than their unsaturated

analogs. They also showed that depending on the plasma reaction

conditions (i.e. power, pressure, and monomer flow rate), polymers in

the form of powders, gels, or films could be obtained. Kobayashi et al.

determined specific conditions under which a rigid polyethylene (PE)

film was obtained. Elemental analysis of such plasma-PE indicated a

deficiency of hydrogen as compared to conventional PE (102). This

observation suggested that the plasma PE was highly crosslinked, as is

well recognized now for most polymers made by the plasma polymerization

process (108).

Ho and Yasuda investigated the plasma polymerization of methane onto

PDMS, followed by a wet oxygen treatment (109). The thin, tightly

crosslinked, and wettable oxidized hydrocarbon coating formed on the

surface of PDMS was shown to be an effective barrier to diffusion of

large dye molecules. Because of the hydrophilic nature of the coating, a

significant decrease in the friction coefficient was also observed (109)

The application for such plasma treatment was for contact lenses. The

significance of this work is that less damage to the cornea as well as

less absorption of biosubstances present in tears was expected.

The plasma polymerization of NVP onto PMMA for IOL applications was

first studied by Sheets, in this laboratory (5). The hydrophilic

surfaces obtained demonstrated, in in-vitro studies, that adhesion force

and damage to tissues such as the rabbit corneal endothelium were












significantly reduced as compared to unmodified PMMA surface (5).

Similar studies were recently reported by Marchant et al. where plasma

PVP coatings on silicone and germanium mirrors were produced. Their

FT-IR/ATR and XPS studies have shown evidence that the plasma PVP films

are highly branched and crosslinked and contained slightly more oxygen

on the surface than linear PVP homopolymer (110).

2.4.5.2.2 Plasma treatment

For plasmas excited in inert gases such as argon or helium as the

sustaining medium, the reactions initiated on a polymer surface are

thought to involve excited states of the polymer chain which undergo

homolytic bond cleavage on deexcitation, producing a wide variety of

free radicals (111,112). An early study by Bamford and Ward showed

that the plasma-formed surface radicals may be used directly or

indirectly to initiate graft polymerization of vinyl monomers in a

manner similar to the preirradiation grafting discussed in section 2.4.4

(112).

Triolo and Andrade have made a detailed study of surface

modification by RF plasma of double catheter systems. These consist of

stiff outer catheter and flexible inner catheter materials including

PDMS, PE, PVC, and FEP (104). In an attempt to reduce the friction

between the two catheters, they oxidized the polymers in a helium

environment followed by exposure to air. Their results indicate

increased oxygen concentration at the polymer surfaces and decreased

air-water contact angles as plasma exposure time was increased (keeping

all other parameters constant). The hydrophilic surfaces produced were

stable for up to 3 months storage in air. However, the significance of













this result under dynamic test conditions (i.e., friction) was not

addressed.

In the particular case of PDMS, Triolo and Andrade concluded from

their XPS data that the plasma treatment increased the oxygen content on

the surface while the silicone content remained roughly unchanged.

Since the pendant -CH3 groups dominate the PDMS surface, it is suggested

that oxidation is to a Si-CH20H structure rather than Si-OH, although

some of the latter undoubtedly forms as well (Equation 2.18). Some

hydroxylation may also occur via peroxide formation due to reaction of

-CH3 groups with oxygen (104). Formation of surface crosslinking

between chains is also possible through recombination of radicals (101)

A study by Clark and Wilson examined the selective surface modification

of various polymers by means of low-power RF plasmas excited in hydrogen

and oxygen (113). They reported that selective alteration of a polymer

surface can be achieved both in terms of extent of reaction and the

range over which the surface modification occurs (113). They showed for

instance, that the oxygen plasma introduced a wide variety of oxidized

functions, while the hydrogen plasma treated samples did not reveal any

significant changes with respect to control samples. In addition, Clark

and Wilson were able to draw some valuable conclusions from their

extensive angle resolved XPS analysis showing how powerful this

technique could be for delineating the first monolayers from the

subsurface and bulk of the sample (113). However, in this study, they

did not address the problem of stability of the plasma treated surfaces.

Since their samples were not exposed to air after plasma treatment,


















CH3
I
-(-Si-O)n-

CH3




inert gas
plasma




CH2 *CH2

- (-Si-O)n- -Si-O"

CH3 CH3



air

moisture

C2H


CH2OOH

- (-Si-O)n--

CH3


CH20H

---Si-OH
I
CH2

CH2

~- (Si-O) --

CH3


(2.18)













therefore not washed, it is possible that their XPS data relate to

plasma degradation products rather than permanently modified surfaces

(114).

Vargo et al. studied the extent and nature of surface modification

of PMMA in H20 and 02/H20 plasmas (115). Extensive surface

characterization was carried out using XPS, FT-IR/ATR, ISS (Ion

scattering spectroscopy) analyses, and contact angle measurements.

Information derived from their data indicate that the greatest depth of

modification is less than 20 A for both plasmas. Their XPS, ISS and

FT-IR/ATR analyses also seem to indicate that the 02/H20 plasma oxidizes

PMMA surface more than the H20 plasma does, based on the oxygen content

and oxygen functionality on the surface. The contact angle

measurements, however, show that the H20 plasma creates a more polar

surface (lower contact angle) than the 02/H20 modified surfaces. Based

on the experimental data available, Vargo et. al proposed simple models

for the surface modification of PMMA by 02/H20 and H20 plasmas. These

models are illustrated in equations 2.19 and 2.20. Similar results were

reported earlier by Nuzzo and Smolinsky on surface modification of PE by

H20, 02 and H2 plasmas. They revealed that under the same experimental

conditions, the water plasma yielded the more polar surface (116)

2.4.5.2 Plasma/Gamma-induced graft polymerization

In the course of this research, various polymers have been

investigated with respect to hydrophilic surface modification.

Generally, graft polymerization of polar vinyl monomers in a polar

solvent onto an apolar substrate results in very low grafting yields.

This is mainly because the overall grafting process is diffusion-











controlled; that is, the observed grafting rate strongly depends on the

monomer concentration available at the polymer surface. Generally,

entropically driven processes play major roles at polar/apolar

interfaces, resulting from hydrophobic repulsions between the apolar

substrate (e.g. PMMA, PDMS, PP, PVDF) and the polar polymerizing monomer

solution (e.g. NVP/H20). Consequently, the concentration of monomer at

the solid-liquid interface is generally low.

Therefore, for a graft polymerization to proceed efficiently in a

heterogeneous system some definitive interactions between the substrate,

the solvent, and the monomer are necessary; i.e. the active sites

produced on the substrate, by radiolysis, should be accessible to the

monomer. This problem has been investigated in this research and we

have demonstrated with the "Presoak Method" that a thermally enhanced

diffusion of the monomer into the polymer subsurface reduces the

entropic effects and results in higher graft polymerization efficiency

of NVP on PMMA, PDMS, PP, and PVDF.

A second novel method was also investigated in the present research

and has been found to overcome, in different ways, the limitations of a

simple gamma radiation grafting. This method consists of a combined RF

plasma treatment and gamma radiation-induced graft polymerization, and

is referred to as the "Plasma/Gamma Method" (117). The rationale behind

this approach for surface modification of polymers rested on six

factors. First, by using RF plasma oxidation, functionalization should

be restricted to the polymer surface. Second, uniform and high density

polar functions can be generated regardless of surface structural






















CH3 CH3 COOCH3 CH3
SI I
- -CH2 C CH2- C-CH2-C-CH2- C- CH2 -
OCH I IOC
COOCH3 COOCH3 CH3 COOCH3


02/H20 plasma


OH OH O OCH3
I i II
- -CH2- C-O-CH2- C CH2- O- C-CH2- C-CH2--
COOCH3 OH COOH


CH3 CH3 COOCH3 CH3
I I I
--CH 2-C--CH2- C-- CH 2 - CH2'C-CH2-
i I I
COOCH 3 COOCH 3 CH 3 COOCH 3


H20 plasma


OH OH OH OH
I I I I
--CH2-C--CH2 C--CH2-C-CH2-C-CH2--
COOCH3 COOH CH3 COOH


(2.19)


(2.20)













heterogeneities. Third, a more polar surface has a better affinity for

water and polar monomer, and thus a higher concentration of monomer is

expected at the solid-liquid interface. Fourth, upon gamma-irradiation,

graft polymerization shall be restricted to the oxidized layers in which

the reactive sites generated by radiolysis are more accessible to the

monomer. Fifth, although plasma treated substrates yield complex

chemistries when exposed to air, a high proportion of reactive sites are

expected to be converted to the peroxide form. Their radiolytic

decomposition in the presence of a vinyl monomer then provides an

attractive method for surface graft polymerization. Sixth, and one of

most important factors favoring this process, the "Plasma/Gamma Method"

can be applied to ceramics and metals as well as polymers (117)

















CHAPTER 3
MATERIALS AND METHODS



3.1 Materials

3.1.1 Substrates

The surface modification of several polymers of interest for IOL

applications were investigated in this research. These include PMMA

(UVEX, from Pharmacia), PDMS (KE-1935, from Shin-Etsu Silicones of

America), PP (compression molded Prolene fibers, from Ethicon, Inc.),

and PVDF (3 mil Kynar 720 film, from Pennwalt). These substrates were

all generously provided by Pharmacia Ophthalmics, Inc., Pasadena, CA.

Samples were usually cut into rectangular strips of approximately

2
1x5 cm2. PMMA and PDMS IOLs with 6mm optics were also provided by

Pharmacia Ophthalmics, Inc.




3.1.2 Monomers and Reagents for Surface Grafting

A series of hydrophilic vinyl monomers were investigated for graft

polymerization onto PMMA, PDMS, PP and PVDF. These monomers include:

N-2-vinylpyrrolidone (NVP, from Kodak), methacrylic acid (MAA, from

Aldrich), and dimethylacrylamide (DMA, from Polysciences). They were

purified by distillation under reduced pressure (1-2 mm Hg at 55-600C),

and stored at 40C until use. Potassium 3-sulfopropyl acrylate (KSPA),

and 2-acrylamido-2-methyl-l-propanesulfonic acid (AMPSA), were obtained

from Aldrich, and used as received. Sodium methacrylate (SMA), and













Table 2. Chemical structures of monomers and reagents used for
surface grafting.


CH3
/3
MAA H2C C

COOH


CH3
/






O
0

C- N(CH3)2

H2C=c


DMA


KSPA HC/
KSPA H2C-C
k


H



COO -4CH24- SO3 K +
3


0

C- NH2

AM HH2CZC
2- \


0

C-


H CH3
I I
N- CH -(CH222 SO3


AMPSA H2C=C
k


CH3

PEGMA H2C=C

COO -CH2- CH2- O -n O-CH3


Heparin


j0


NHSO3 OSO3


\ N O


NVP


H2CC \


ii












methoxy-polyethylene glycol monomethacrylate (PEGMA-1000 and PEGMA-400)

were obtained from Polysciences, and used as received. Acrylamide (AM,

from Fisher) was purified by recrystallization from chloroform. Heparin

(HEP) was from Sigma Chemical Co. and was used as received. The

structures of the monomers and reagents are indicated in Table 2.




3.2 Methods



3.2.1. Sample Cleaning and Preparation

3.2.1.1 Substrate cleaning before grafting

In order to remove any surface contamination, all substrates used

were systematically cleaned. PMMA slabs, precut to appropriate sample

size, were first sonicated in a 0.1% Triton X-100 (Fisher) aqueous soap

solution for 20 minutes, then followed by a thorough rinse in warm

(ca. 600C) distilled water, and finally sonicated three times (10

minutes each) in distilled water at ambient temperature. PP and PVDF

films were sonicated for 20 minutes in 2-propanol, followed by a similar

procedure as PMMA cleaning. PDMS strips were sonicated two times for 20

minutes each in a 1:1 acetone/ethanol mixture. IOLs (PMMA and PDMS)

were sonicated once for 20 minutes in distilled water. After the

cleaning procedure, all substrates were dried under vacuum (10-2 torr,

600C, 6 hrs.), and were finally stored in a desiccator until further

use.

3.2.1.2 Substrate cleaning after grafting

The grafted substrates were removed from the gamma-polymerization

solution and washed according to the following standard procedure:

i) thorough rinse with hot (600C) distilled water; ii) soak in distilled












water, at ambient temperatures for 3 days with 3 changes of water per

day; iii) dried to constant weight in vacuum (typically at 10-2 torr,

600C, 12 hrs.), then stored in a desiccator until further use or

characterization.

3.2.1.3 Degassing of monomer solutions

The samples comprising the aqueous monomer solutions and the

substrate were prepared in borosilicate test tubes. Before gamma

irradiation all samples were systematically degassed, unless otherwise

indicated, by the following standard procedure : the test tubes were

degassed in vacuo (ca. 10-2 torr) in combination with intermittent

sonication; this usually took from 5 to 20 minutes per sample, depending

on the substrate and the type of monomer. After degassing, the samples

were brought up to atmospheric pressure by argon bleeding and the test

tubes were sealed with polyethylene snap caps. The samples were then

gamma irradiated to appropriate doses.



3.2.2 Gamma-Induced Graft Polymerization of Hvdrophilic Vinyl Monomers
onto Hydrophobic Polymeric Surfaces

3.2.2.1 Presoaking

In this research a novel method was developed which involved

presoaking the substrate in the monomer prior to gamma irradiation. The

basic feature of this method is an immersion of the substrate in monomer

or concentrated aqueous monomer (i.e. NVP) at slightly elevated

temperatures (I 600C) Both higher monomer concentrations and elevated

temperatures enhance monomer diffusion into the subsurface of the

substrate. This presoaking creates a monomer-rich interface which

promotes the formation of an interpenetrating network between the













substrate top surface and the gamma-induced polymerized vinyl monomer

(100).

The presoak procedure was -typically carried out as follows: The

weighed substrate was placed in a borosilicate test tube containing the

appropriate monomer solution and then placed in a temperature-controlled

water bath. The factors which have been found to affect the monomer

uptake by the substrate are the chemical nature of the monomer, its

concentration, the temperature, and the time. All these parameters were

investigated in detail with the PMMA/NVP/water system, and the results

were applied to other substrates such as PP, PVDF, and PDMS.

In addition, the presoaking in NVP was used to graft-polymerize

ionic monomers which are normally resistant to surface grafting when

used alone. The "Presoak Method" was also applied to tailor surface

grafts in the form of multicomponent graft copolymers which mimic the

surface chemical structure of natural membranes and proteins.

3.2.2.3 Gamma-induced graft polymerization

Following the presoaking, and prior to gamma irradiation the

substrates were immediately transferred to a monomer solution with lower

monomer concentration, unless otherwise indicated. The samples were

then degassed by vacuum and argon sparging and tightly sealed under

argon with polyethylene snap caps. Irradiation was conducted by

simultaneously exposing the substrate and the monomer solution to a 600

Curie 60Co gamma source, at room temperature. A schematic diagram of

the gamma source is shown in Figure 5. Radiation doses were varied from

0.05 to 0.2 Mrad. This was achieved by appropriate combination of dose


































I Beam (Door Track)


- Support
Rod


Turret
(Source
Housing)


Door
Cutaway


Figure 6. Schematic diagram of the 60Co gamma source.
(source: adapted from ref. 118).


Door












rate and exposure time. The samples were held such that they were

submerged in the polymerizing medium. The test tubes were held upright

standing in small plastic holders placed typically at a distance of 4

inches, unless otherwise indicated, from the source; corresponding to a

dose rate of 701 rad/min. as determined by Fricke dosimetry (8). After

completion of the grafting, the substrates were removed from the

solution and washed in water according to the standard procedure

described in section 3.2.1. The samples were then dried overnight in

vacuo at 600C and stored in a desiccator until characterization.

3.2.2.2 Two-step gamma-induced gamma grafting

In order to minimize the radiation dose, a two-step irradiation

technique has been adopted whenever materials which are potentially

radiation sensitive (i.e. heparin) were incorporated into the graft.

The following procedure was adopted:

Step I:

a. presoak in 40% NVP, at 600C for 4 hrs.,

b. immediately transfer to 15% NVP, degas,

c. gamma irradiate to 0.09 Mrad at 701 rad/min.,

d. remove substrate from the solution, rinse with distilled water, then

dry to constant weight at 600C under vacuum.

Step II:

a. put dried pregrafted substrate in a solution of the monomer and

other components (i.e. heparin or chondroitin sulfate) to be

incorporated into the graft.

b. degas

c. gamma irradiate to 0.06 Mrad.

d. remove samples from the solution, wash and dry to constant weight.













3.2.3 Glow Discharge RF Plasma Surface Modification

3.2.3.2 Plasma reactor

The RF plasma system, illustrated in Figure 7, consists of a

vertical "bell-jar" reaction chamber, a vacuum system, and a monomer/gas

inlet system. The reaction chamber is inductively coupled by 10 turns

of 4 mm copper tubing to the RF power supply (RF Plasma Products, model

HFS 401 S), which operates at a fixed frequency of 13.56 MHz with a

maximum output of 500 Watts (W). A matching network was used to match

the impedance of the plasma discharge to the RF generator. The reaction

pressure of the plasma discharge is continuously monitored using a

thermocouple vacuum gauge located at the lower part of the chamber. Gas

flow was controlled by a very fine metering valve (Nupro). The chamber

was evacuated by a mechanical pump connected through a liquid nitrogen

cold trap. Liquid reagents were held in 20 ml long-necked round-bottom

flasks and vaporized into the reactor through a vacuum manifold (Figure

6).

3.2.3.2 Plasma treatments

The substrate samples were placed horizontally on a glass plate

positioned at ca. 5 cm from the lower part of the chamber neck. After

mounting the samples, the chamber was evacuated to a pressure of ca. 10

mTorr and maintained for at least 30 minutes. The pressure was then

brought up to ca. 150 20 mTorr by introduction of water vapor. In

order to minimize contamination and insure reproducibility, several

































































Figure 7. Schematic drawing of the RF Plasma apparatus.












purge cycles were carried out with the appropriate gas, after which a

constant gas flow was maintained and the RF power switched on. Polymer

samples were modified under various conditions of time (1-30 minutes),

power (5 to 50 Watts), and in presence of water vapor. The glow

discharge extended throughout the reaction chamber. The intensity of

the glow discharge increased with increasing power input. The reaction

temperature was not controlled in these experiments. At the end of the

reaction period, the RF power was turned off, the initial pressure of 10

mTorr was restored and maintained for 15 minutes, and then raised to

atmospheric pressure using air. Treated samples were retrieved from the

reactor and were cleaned by ultrasonication in water to remove low MW

fragments from degradation reactions, and other contaminants weakly

adsorbed to the surface. This cleaning allows for a more accurate

analysis of permanent surface modification.




3.2.4 Combined Plasma/Gamma-Induced Surface Modification

The use of gamma radiation and RF plasma techniques have been

investigated for surface modification of polymers in the past. The

inherent advantages and disadvantages of these techniques have been

discussed in Chapter 2.

A unique combination of plasma treatment with gamma-induced grafting

was investigated in the present work. This method referred to as the

"Plasma/Gamma" process overcomes many limitations of both RF plasma and

gamma radiation graft polymerization for surface modification.

The surface modification effected by the "Plasma/Gamma" technique

involves an initial plasma oxidation or activation of the surface as

described in section 3.2.3.2. The sample is then immersed in a degassed













aqueous monomer solution (e.g. 10 Wt.% NVP), and gamma irradiated to

doses as high as about 0.15 Mrad. The grafted substrates are removed

form the gamma graft homopolymer solution and thoroughly washed

according to the procedure described in section 3.2.1.

To the best of our knowledge, this combination of RF plasma with

gamma radiation for surface modification of solid materials has not been

reported in the literature, and a patent application for this versatile

process has been filed (117).



3.2.5 Characterization

3.2.5.1 Gravimetric analysis

Gravimetric analysis is a simple, convenient, inexpensive and

information-rich analytical technique that was used in this research.

All weights were determined using a Sartorius Research electronic

balance (model R 200 D) having a precision of : 0.02 mg. The dry

weights of three replicas were averaged. The grafting yield was

determined by the percentage increase in weight:

Wt.% graft = (Wg-Wo/Wo)x100 (3.1)

where Wo and Wg are the dry weights of initial and grafted substrate,

respectively. However, depending on sample geometry (surface:volume

ratio) weight changes of less than ca. 1% may not be meaningful.

3.2.5.2 Contact angle

Contact angle measurement is one of the simpler, non-damaging

surface sensitive techniques which gives information on the outermost

few monolayers of solid polymer surfaces. This technique is one of the





















Sample ----

Air
Bubble


sl


--i-- Glass Slide

------ Contact Angle



....-. Transparent
Plastic Container

---- Distilled Water


Ylv


S sv


solid


(b)


Figure 8. Schematic representation of the captive air bubble
contact angle measurements:
(a) immersion chamber
(b) air bubble at the solid-water interface













most useful methods of characterizing solid/liquid interfaces (119,120).

It is used to elucidate the extent of surface wettability and

homogeneity before and after surface modification. The contact angle is

related to the solid-vapor (ysv), solid-liquid (1sl), and liquid-vapor

(Ylv) interfacial free energies via the Young's equation (119), i.e.

cos 0 = (Ysv Ysl)/Ylv (3.2)

Contact angles were measured on a Rame-Hart contact angle Goniometer

(Mountain Lakes, New Jersey), at room temperature, in distilled water,

usually using the captive air bubble technique. Typically the substrate

is held to the underside of a microscope glass slide with rubber bands,

and the slide is put across an acrylic immersion chamber filled with

double distilled water. Figure 8 illustrates how the contact angle was

measured. The substrates were equilibrated for approximately 3 hours

before measurement to ensure complete surface hydration. A microsyringe

containing air was used to form air bubbles underneath the hydrated

surface. Typically, the contact angles of six air bubbles across the

surface, measured on both sides of the bubble, were averaged.

3.2.5.3 FT-IR/ATR

Fourier-transform infra-red (FT-IR) with attenuated total

reflectance (ATR) is another tool for surface characterization of

polymers and has been one of the most popular methods for sensitive

surface spectroscopy (122).

The advantages of FT-IR/ATR as a surface analytical method is its

ability to give information on surface chemical composition and chemical

structure and bonding. FT-IR/ATR has had a relatively long history of















To detector


Crystal (n ) ..

Sample (n1) ------


---- Sample (n)







From IR
source


Figure 9. A typical optical diagram for attenuated total
(ATR) spectroscopy.












hv


reflectance





















, Ejected
photoelectron


Figure 10. Schematic view of the interaction of an X-ray photon
with an atomic orbital.













use in the biomaterials field particularly the study of surface

modification of polymers (122). Figure 9 shows a schematic optical

diagram for ATR spectroscopy.- The capabilities of FT-IR/ATR for surface

analysis is due to the penetrating nature of IR and total reflection

from the internal reflecting element (IRE) crystal/sample interface into

the sample. The depth at which the incident IR beam decays to 1/e of

its initial value is defined as the depth of penetration (dp) and is

described by the relation




dp = (3.3)
2 T n1 [sin2 8 n2/nl]1/2



where A = wavelength of the IR radiation

nI = refractive index of the IRE crystal (ZnSe = 2.4)

n2 = refractive index of the sample

0 = angle of incidence and exit of IR beam.

The surface depths probed therefore range from 0.5 to 3 pm depending on

X, n1, n2, andO. A depth profile can theoretically be obtained by

collecting sample spectra at various angles of incidence of the IR beam

and using various IRE crystals, e.g. Ge (n=4.0), ZnSe (n=2.4), KRS5

(n=2.38), etc.

The FT-IR/ATR spectra were obtained with a Nicolet 60SX

spectrometer typically using a parallelogram ZnSe crystal

(50mmx10mmx2mm, from Spectra Tech), unless otherwise indicated. Two

samples (1x2 cm2) were pressed against the IRE crystal which had an

entrance and exit face angle of 600. A depth profile study was carried











out using ZnSe (600), KRS-5 (450), and Ge (450) IRE crystals. Typically

100 scans at a resolution of 4cm-' were signal averaged. All data

processing was done with standard Nicolet software provided with the

instrument.

3.2.5.4 XPS

X-ray photoelectron spectroscopy (XPS), also known as electron

spectroscopy for chemical analysis (ESCA) is an invaluable technique for

studying the chemical composition of polymer surfaces. XPS is a

relatively new analytical tool which provides information on chemical

structure and bonding and can provide quantitative, and readily

interpretable data regarding the composition of the uppermost surface of

materials (123). For these reasons, XPS has been widely used for the

analysis of biopolymers (123,124).

The basic principle of XPS is the photoelectric effect which

measures the kinetic energy of electrons emitted by the atoms on a

material's surface when they are bombarded with an X-ray beam, in an

ultra-high vacuum environment (Figure 10). The emitted electrons are of

low energy and are easily scattered when travelling through the solid.

Therefore, XPS surface sensitivity is due to the fact that only

electrons emitted near the surface have a reasonable chance of escaping

without suffering energy losses. The binding energy of an emitted

electron is obtained from the following equation,

Eb = hV-Ek-D (3.4)

where Eb is the electron binding energy, Ek is the electron kinetic

energy measured by the instrument, hv is the photon energy (h is the

Plank's constant and V is the X-ray frequency), and ( is a work

function established for each spectrometer (124). All energies are













expressed in electron-volts (eV). The observed Eb of an electron is

indicative of the element from which it was ejected and the chemical

environment of that element. All atoms, except H, can be analyzed by

XPS and identified according to their specific binding energies.

The XPS data was acquired using a Kratos model XSAM-800 spectrometer

with an Mg K, X-ray source. The X-ray gun was operated at 20 kV and 23

mA and the pressure in the analyzer chamber was 10-7 to 10-8 torr. All

data were processed by using the standard software (DS800) provided with

the instrument. In all cases, surface-charging had no significant

effect on the peak resolution and only a slight shift towards higher

binding energies was usually observed. Thus, no flood gun was used. The

binding energy scale was corrected by calibration of the hydrocarbon Cls

peak set at 285 eV. The quantitative analysis was performed using

Scofield photoelectron cross-sections, FRR (fixed retarded ratio) mode

and an E-1 transmission function. Variable angle XPS was employed to

characterize the depth of polymer surface modification. The sample

depth that photoelectrons can traverse before undergoing inelastic

scattering is defined as the mean-free path, X. The mean sampling depth

for flat samples, d, is

d = A sin 6 (3.5)

where 0 is the photoelectron take-off angle measured relative to the

plane of the sample surface (Figure 11).

3.2.5.5 Light microscopy

Graft thickness, surface topography and biological in-vitro tests

were studied using light and scanning electron microscopy. Optical

micrographs were obtained using a Nikon optical microscope.
























X- Xsin 0


7-


Figure 11. Schematic drawing on the effect of sample tilt angle on
depth of XPS analysis












3.2.5.6 SEM

Surface morphological data were obtained using a scanning electron

microscope (JEOL JSM-35CF SEM). The surfaces were coated with gold-

palladium using a Hummer V sputter-coater (Technics, Alexandria,

Virginia). Typically an accelerating voltage of 10 kV was used. Varied

magnifications were employed to best reveal surface morphological

differences.




3.2.6 In-Vitro Studies

3.2.6.1 Lens epithelial cell adhesion and spreading

Rabbit lens epithelial cell adhesion and spreading methods were

developed by Hofmeister, of this laboratory. This test was performed by

Hofmeister, and experimental details may be found in his thesis (62).

Lens epithelial cells, cultured from the lens anterior capsule of white

rabbits were used. Quantitative adhesion and spreading of cells on the

various substrates was performed on a Nikon inverted microscope equipped

with a video camera coupled to an IBM XT computer interfaced with a

digital image enhancement and analysis system. Three to five fields of

view, 0.298 mm2 in area, were sampled on each replicate and the number

of cells per field were recorded.

3.2.6.2 Iris abrasion

The iris-IOL abrasion test was also developed by Hofmeister, and

experimental details are described in his thesis (62). The iris-

abrasion apparatus is shown in Figure 12. An NRC oscillating electronic

stylus (Newport Corp., Fountain valley, CA) was connected to a 2 MHz

function generator (Wavetek San Diego Inc., San Diego, CA) to control

the frequency and amplitude of the stylus movements. The plano-convex













IOLs were fastened to the tip of the stainless steel stylus via acrylic

stubs to which they were glued on the flat side. The posterior surface

of pigmented irides from Dutch Belt rabbits (2-3 Kg) were abraded in the

radial direction under saline solution. The generator signal was set in

the sinusoidal mode. Hofmeister determined that the damage threshold

region was approximately 1,000 abrasion cycles for a load of 0.656 to

0.681 grams applied at the center of the IOL; thus comparative studies

of modified and unmodified IOLs were generally carried out under those

conditions (62). Testing of the samples, prepared in this research, was

carried out by Hofmeister (62). Iris damage was assessed by SEM and

optical microscopy.

3.2.6.3 Corneal endothelial cell damage

It was first shown in this laboratory that accidental physical

contact and adhesion between a PMMA IOL and the corneal endothelium,

during or after surgery, can cause irreversible damage to the

endothelial cells. In order to assess such damage an instrument (shown

in Figure 13) and an in-vitro method were developed in this laboratory

by Reich et. al. (125). The instrument was designed to allow both

measurement of the adhesive force and to provide quantitative

measurement of endothelium damage due to contact with polymer surfaces.

Preparation of polymer surfaces and corneas have been described

previously (5,6,62,126). Testing of the samples prepared in this

research was carried out by J.Stacholy of this laboratory, and

experimental details are well described in his thesis (126). Damage to

corneal endothelial cells was assessed by SEM and light microscopy.








































Function Generator (2MHz)


oscillating stylus

I


IOL


69











Sderal Ring







lasting Stylus
Lens Sample Mount

Saline Test Reservoir




















iris


saline
.- reservoir


Figure 12. Schematic description of the iris abrasion test instrument.


























Adjustea Suppor
Stag tor
Tripod Weight


X-Y Micrometer Stage
(for centering of matenai
sample over andothelium)


Microscooe Base


Figure 13. Drawing of the corneal endothelium damage test instrument.


















CHAPTER 4
RESULTS AND DISCUSSION


4.1 Hvdrophilic Surface Modification of IOL Polymers by an Improved
Radiation-Induced Graft Polymerization Method: The "Presoak Method"


Studies carried out in this laboratory by previous workers led to

the suggestion that hydrophilic surface modification of polymers used

for biomedical implants and devices had a potential advantage in

reducing tissue trauma and improving biocompatibility (3-6). This study

deals with improved synthetic procedures for hydrophilic surface

modification of IOL polymers by radiation-induced graft polymerization.

Radiation-induced graft polymerization involves a heterogeneous

polymer-monomer reaction system and the rate of polymerization is

usually diffusion-controlled (95). Therefore, a high concentration of

monomer at the polymer/solution interface is of prime importance if a

high degree of grafting is to be obtained. A way of achieving such a

high interfacial concentration of monomer is to facilitate its

diffusion, to some extent, into the polymer subsurface. This has been

achieved by using the "Presoak Method" previously described in section

3.2.2.1. This method allows synthesis of covalently bonded, uniform and

optically clear surface grafts without dimensional and structural

distortion of the ocular implant.

The following sections discuss the various aspects of the Presoak

Method as applied for hydrophilic surface modification of PMMA, PP,

PVDF, and PDMS.













4.1.1 Sorption Behavior of PMMA, PP. PDMS and PVDF in NVP: Monomer
Uptake


PMMA is the major material used for manufacturing IOLs; thus the

sorption behavior of PMMA during presoak in aqueous solutions of NVP was

studied in detail, while only some conditions were evaluated for PP,

PVDF, and PDMS.

The weight gain of PMMA as a function of temperature, monomer

concentration and time is given in Figures 14-17, and numerical data are

summarized in Table 3.

4.1.1.1 Effect of temperature

Figure 14 shows the solution uptake of NVP by weight as a function

of temperature for PMMA slabs (20 mm x 10 mm x 3 mm) soaked in a 40% NVP

water solution for 4 hours. At room temperature, no significant weight

gain was observed which is consistent with the low diffusivity of small

molecules in rigid glassy polymers. Moreover, hydrophobic repulsions

between the relatively apolar substrate and the polar aqueous phase

impart a high activation energy for the diffusion of the monomer into

the PMMA subsurface.

At higher temperatures, however, it is shown in Figure 14 that the

monomer uptake increases as temperature increases. This can be

explained by the lowering of the activation energy for diffusion by

thermal energy input into the system. The temperature-dependence of the

diffusion coefficient (D) is generally described by an Arrhenius form,

i.e.

D = DO exp(-Ea/RT) (4.1)

where DO is a constant characteristic of the system, Ea is the



























%,o WEIGHT
INCREASE


20 30 40 50 60 70

TEMPERATURE (C)


Figure 14. Effect of temperature on weight uptake by PMMA soaked in
40% NVP for 4 hrs.













activation energy for the diffusion process, R is the the molar gas

constant, and T is the absolute temperature (127).

From Figure 14, it can be seen that up to ca. 450C a slow and steady

increase in the monomer uptake by PMMA takes place while above 450C, a

break in the curve occurs with a drastic increase in weight gain as the

temperature approaches 600C. The sharp increase in the curve over a

relatively narrow temperature range suggests that some type of molecular

motion is unfrozen and a relaxation process is initiated (128). At room

temperature, molecular mobility in glassy polymers is usually very

restricted because of intermolecular forces and steric hindrance to

internal rotation of side groups. However, at higher temperatures and

below Tg, the various structural segments acquire sufficient thermal

.vibrations to induce some local and/or large-scale motions of the

polymer chains (128). Below Tg, the mechanisms of these relaxation

phenomena are still not well understood (128).

Relaxation phenomena in PMMA have been studied by Callejo et al.,

from the perspective of thermal effects and aging on PMMA (129). They

observed that structural relaxation phenomena take place in the zone

between Tg and the first of the secondary relaxations (0 relaxation),

occurring at 460C (127). The molecular motions associated with this

relaxation have been attributed to both rotation of the ester side

groups and motion of the main chain (127).

Relaxation processes lead to increased chain mobility and to

"opening" of the physical structure of the otherwise rigid PMMA, thereby

enhancing free volume effects for the polymer. Free volume and polymer

















Table 3. Weight uptake by PMMA as a function of time and solution
composition during presoak at 600C.



I NVP/H20 I
ratio I 0/100 30/70 40/60 50/50
Time I
(hrs) I Wt% Uptake by PMMA


0.0

1.0

2.0

3.0

4.0

5.0

6.0

8.0

9.0

10.0

12.0

17.0

18.0

21.0

24.0

36.0

48.0

72.0


0.0

1.0

1.2

2.1

2.4

2.9

3.6

3.9

4.2

5.5

5.9

7.4





8.8


0.0

2.5

3.9

6.2

7.3

7.9

10.3

11.5

12.4

13.3

15.2

21.0





27.2


0.0

1.4

1.8

3.5

4.1

5.3

5.4

6.3

7.6

6.6

9.0

11.1

14.2



16.6

16.4

16.2

15.2














chain mobility are major driving forces for diffusional transport in

polymer systems (130).

4.1.1.2 Effect of monomer concentration

The influence of solution composition on monomer uptake by PMMA was

examined. PMMA was soaked in NVP/H20 solutions in ratios of 0/100,

30/70, 40/60, and 50/50 by weight. The temperature was kept constant at

600C. The weight uptake of PMMA was recorded as a function of time for

each solution (Table 3) and results are plotted in Figure 15.

From Figure 15 it can be seen that in pure water, at 600C, and for

24 hours, the weight gain for PMMA is negligible. This low water uptake

by PMMA accounts for the generally low thermodynamic compatibility of

hydrophobic polymers with hydrophilic liquids where activation energies

for diffusion are relatively high, and solubilities are very low. The

overall sorption behavior of PMMA in water observed in this study agrees

well with related studies reported by other researchers.

Turner, for instance, had thoroughly investigated the sorption

kinetics of water in PMMA (131). He determined that at 23.50C the

equilibrium water uptake of PMMA is about 1.2%, and that 50% of that

water clusters in the free volume of the polymer (131). Turner also

determined that the sorption kinetics of water in PMMA followed a dual

mechanism involving accommodation of sorbant in the free volume and

swelling effects (133). Drotning and Roth also studied the effects of

moisture uptake on the dimensional changes of PMMA (132). Their

findings indicate that under equilibrium conditions for a 2% weight

gain, the dimensional swelling of PMMA is only 0.5%, and that the

process is reversible upon drying of the polymer (132).



















30

S50% NVP





20

% WEIGHT
INCREASE
-. 40% NVP


10- y
10^ 30% NVP





_ --a- WATER
0 -<----- i---- ,i ----'i---- ------ -- ----

0 10 20 30
TIME (Hrs)






Figure 15. Effects of NVP concentration and time on weight uptake by
PMMA at 600C.












In the presence of aqueous NVP solutions, on the other hand, the

rate of sorption of PMMA, as indicated by the slopes of the curves in

Figure 15, increases rapidly as the soaking monomer solution is made

richer in NVP. NVP is a versatile monomer which is well known for its

thermodynamic compatibility with various polar and apolar compounds.

Experimentally, pure NVP was observed to swell, craze and even slowly

dissolve PMMA. Conversely, Figure 15 and Table 3 show that water plays

the important role of a diffusion-control agent which minimizes the

excessive swelling and crazing effects of pure NVP on PMMA.

The "excess" chemical affinity of NVP for PMMA could well be

explained qualitatively by invoking its amphiphilic character. NVP is

amphiphilic exhibiting a polar component due to a highly polar amide

group, and a dispersive component due to the four methylene groups.

PMMA also exhibits a relative amphiphilic character, but is

predominantly apolar with only a slight polar character from its ester

side group. Thus, interaction between NVP and PMMA mainly involves

dispersive (or apolar) forces, and polar forces to a much lesser extent.

As the NVP concentration increases, dispersion and polar forces become

more pronounced and help to disrupt the cohesive forces between the PMMA

chains. In addition, and as previously mentioned, enhanced polymer

chain mobility due to thermal effects enhances further diffusion of

monomer into PMMA.

The shape of the various plots in Figure 15, appear nearly the same.

This suggests that overall interfacial diffusion occurs according to the

same mechanisms regardless of monomer concentration which affects only

kinetic aspects.













An interesting feature to note in Table 3 and Figure 15 is that no

changes in optical properties of PMMA occur until nearly 7 to 8% of

monomer has penetrated into the polymer. Beyond 8% weight uptake, PMMA

usually becomes hazy. This aspect has not been fully investigated in

this research, but it is suspected that the haziness develops as a

result of phase separation and cluster formation. When the clusters

reach a certain size they scatter light. It is also possible that

crazing may contribute to this haziness.

Nevertheless, haziness can be minimized even at 8% weight uptake if

the samples are quenched fast enough ( 15 seconds) from 600C to room

temperature. This way, all molecular motions and rearrangements leading

to phase separation are minimized. Furthermore, it was found that even

slightly opaque samples during presoak (8-10 wt% monomer uptake), become

transparent following gamma-induced graft polymerization.

4.1.1.3 Effect of time

The dependence of NVP monomer uptake on time at fixed solution

composition (40% NVP) and constant temperature (600C) is presented in

Figure 16. Overall weight uptake attains a maximum and then levels off

though presoaking slightly to a lower value. The high initial rate of

sorption is evident by the maximum attainment uptake of 16.6 % within

the first 24 hours. The shape of the curve indicates a release of

sorbant during presoak after saturation is reached. Turner has also

reported similar behavior for PMMA soaked in water for extended periods

of time. Turner observed that water penetrates as a front from the two

surfaces of the PMMA slab (20 mm x 10 mm x 3 mm) and that equilibrium is

reached when the two fronts meet (130).




















20









% WEIGHT
INCREASE
10












0-9
0 -c --- ,-i ------:- ---------

0 20 40 60 80
TIME (Hrs)


Figure 16.


Effect of time on weight uptake by PMMA soaked in 40% NVP at
600C.



















LU
U



0
Z




CD


0r
*r-


1775


1-75


1 75


ab


4000


3270


1810


o100


WAVENUMBER

Figure 17. FT-IR/ATR spectrum for unmodified PMMA and expansion of
the 1775-1575 cm"1 region.

Table 4. Main FT-IR/ATR absorption bands for PMMA.


V(cm-1) peak assignment

2950 a -CH2- assym. stretch

2844 b -CH2- sym. stretch
0
1725 c -C-O- stretch

1110-1082 d -C-O-C stretch


N'


I -


ttl
r















C


-- 77
S -^



U
ZN
7N
h-
0n

(r LO
S f1775 1675 1575





4000 3270 250 1E
IAVENUMBE





Figure 18. FT-IR/ATR spectrum for NVP-soaked PMMA
(40% NVP/600C/4 hrs) .


I


I U
F













Figure 17 shows the FT-IR/ATR spectrum of unmodified PMMA with the

1775-1575 cm1 region expanded. Table 4 shows the assignment of most

pertinent peaks of PMMA. Figure 18 shows the FT-IR/ATR spectrum of the

blotted NVP-soaked PMMA. Soaking was carried out in 40% NVP at 600C for

4 hours and monomer uptake was 4.1 wt%. The important feature arising

from this spectrum is the appearance of two new absorption bands

appearing at 1705 cm-1 and 1620 cm1. The former is attributed to the

amide carbonyl, and the latter arises from the vinyl group of NVP.

Moreover, it is interesting to note from Figure 18 that no

significant absorption band is visible in the hydroxyl region centered

around 3200 cm1. Thus one may conclude that, under the presoak

conditions considered here, a selective sorption process takes place in

which the penetrant that had diffused into the polymer is richer in NVP

than the initial solution. The preferential affinity of NVP for PMMA

observed by FT-IR/ATR is consistent with gravimetric analysis

which showed that penetrant uptake significantly increases as the

soaking solution is made richer in NVP (Figure 15 and Table 3).

As shown from these NVP-PMMA sorption studies an NVP-rich interface

is established which allows the monomer to be present as close as

possible near the active centers created in the polymer backbone during

the gamma radiation grafting. The following sections will elucidate the

effects of pre-irradiation monomer soaking on the surface graft

polymerization process.

4.1.1.4 Overall presoak effects

Temperature, monomer-type and monomer concentration are the

governing parameters in the sorption behavior of PMMA. The coupled




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