Radiation Effects On Polymers For Biological Use 3540440208, 9783540440208

Citation preview

162 Advances in Polymer Science

Editorial Board: A. A b e . A.-C. A l b e r t s s o n • H.-]. C a n t o w K. D u ~ e k • S. E d w a r d s - H. H 6 c k e r I. F. l o a n n y • H.-H. K a u s c h • S. K o b a y a s h i K.-S. L e e . O. N u y k e n • S. I. S t u p p . U. W. Suter G. W e g n e r • R. I. Young

Springer Berlin Heidelberg New York Hong Kong London Milan Paris Tokyo

Radiation Effects on Polymers for Biological Use

With contributions by N. Anjum, Y. Chevolot, B. Gupta, D. L6onard, H. J. Mathieu, L. A. Pruitt, L. Ruiz-Taylor, M. Scholz

~ Springer

This series presents critical reviews of the present and future trends in polymer and biopolymer science including chemistry, physical chemistry, physics and materials science. It is addressed to all scientists at universities and in industry who wish to keep abreast of advances in the topics covered. As a rule, contributions are specially commissioned. The editors and publishers will, however, always be pleased to receive suggestions and supplementary information. Papers are accepted for ,,Advances in Polymer Science" in English. In references Advances in Polymer Science is abbreviated Adv Polym Sci and is cited as a journal. Springer APS home page: http://link.springer.de/series/aps/or http://link.springer-ny.com/series/aps/ Springer-Verlag home page: http://www.springer.de

ISSN OO65-3195 I S B N 3-540-44020-8

Springer-Verlag Berlin Heidelberg New York Library of Congress Catalog Card Number 6a642 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, re-use of illustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks. Duplication of this publication or parts thereof is only permitted under the provisions of the German Copyright Law of September 9, a965, in its current version, and permission for use must always be obtained from Springer-Verlag. Violations are liable for prosecution under the German Copyright Law. Springer-Verlag Berlin Heidelberg New York a member of BertelsmannSpringer Science+Business Media GmbH htt p://www.springer.de © Springer-Verlag Berlin Heidelberg 2oo3 Printed in Germany The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Typesetting: medio Technologies AG, Berlin Cover: medio Technologies AG, Berlin Printed on acid-free paper o2/3o2okk - 5 4 3 2 t o

Volume Editor Prof. Dr. H e n n i n g Kausch c/o IGC I, Lab.of Polyelectrolytes and Biomacromolecules EPFL-Ecublens 1015 Lausanne Switzerland E-maR: [email protected]

Editorial Board Prof. Akihiro Abe Department of Industrial Chemistry Tokyo Institute of Polytechnics 1583 Iiyama, Atsugi-shi 243-02, Japan E-mail'. aabe@chem,t-kougei.ac.jp Prof. A n n - C h r i s t i n e A l b e r t s s o n Department of Polymer Technology The Royal Institute of Technology S-10044 Stockholm, Sweden E-maih [email protected] Prof. H a n s - J o a c h i m C a n t o w Freiburger Materia]forschungszentrum Stefan Meier-Str. 21 79104 Freiburg i. Br., Germany E-maih [email protected] Prof. Karel Du~ek Institute of Macromolecular Chemistry, Czech Academy of Sciences of the Czech Republic Heyrovsk~,Sq. 2 16206 Prague 6, Czech Republic E-maR: [email protected] Prof. Sam Edwards Department of Physics Cavendish Laboratory University of Cambridge Madingley Road Cambridge CB30HE, UK E-maih sfel [email protected]

Prof. H a r t w i g H6 c k e r Lehrstuhl ffir Textilchemie und Makromolekulare Chemie RWTH Aachen Veltmanplatz 8 52062 Aachen, Germany E-maih [email protected] Prof. Jean-Franqois J o a n n y Institute Charles Sadron 6, rue Boussingault F-67083 Strasbourg Cedex, France E-maih joanny@europe,u-strasbg.fr Prof. H a n s - H e n n i n g Kausch c/o IGC I, Lab. of Polyelectrolytes and Biomacromolecules EPFL-Ecublens GH-I015 Lausanne, Switzerland E-mail." [email protected] Prof. T. Kobayashi Institute for Chemical Research Kyoto University Uji, Kyoto 611, Japan E-maih [email protected] Prof. Kwang-Sup Lee Department of Polymer Science & Engineering Hannam University 133 Ojung-Dong Teajon 300-791, Korea E-maih [email protected]

VI

Editorial Board

Prof. Oskar N u y k e n Lehrstuhl far Makromolekulare Stoffe TU Mfinchen Lichtenbergstr. 4 85747 Garching

Prof. G e r h a r d W e g n e r Max-Planck-Institut fiir Polymerforschung Ackermannweg 10 Post fach 3148 55128 Mainz, Germany

E-math [email protected]

E-math [email protected]

Prof. S a m u e l I. Stupp Department of Measurement Materials Science and Engineering Northwestern University 2225 North Campus Drive Evanston, IL 60208-3113, USA

Prof. R o b e r t J. Young Manchester Materials Science Centre University of Manchester and UMIST Grosvenor Street Manchester M1 7HS, UK

E-math [email protected] Prof. U l r i c h W. Suter Department of Materials Institute of Polymers ETZ,CNB E92 CH-8092 Zfirich, Switzerland

E-math [email protected]

E-math [email protected]

Preface

By polymers for biological use we understand biopolymers and living matter. Biomaterials are man-made or -modified materials which repair, reinforce or replace damaged functional parts of the (human) body. Hip joints, cardiovascular tubes or skin adhesives are just a few examples. Such materials are principally chosen for their mechanical performance (stiffness, strength, fatigue resistance). All mechanical and biological interactions between an implant and the body occur across the interface, which has to correspond as nearly as possible to its particular function.A natural surface is a complex (three-dimensional) structure, which has to fulfil many roles: recognition, adhesion (or rejection), transport or growth. We have to admit that at present biomaterials are far removed from such performance although new strategies in surface engineering have been adopted in which man tries to learn from nature. Much of the progress in adapting polymer materials for use in a biological environment has been obtained through irradiation techniques. For this reason the most recent developments in 4 key areas are reviewed in this special volume. All surface engineering necessarily begins with an analysis of the topology and the elemental composition of a functional surface and of the degree of assimilation obtained by a particular modification. X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectroscopy (ToF-SIMS) play a prominent role in such studies and these are detailed by H.J. Mathieu and his group from the Ecole Polytechnique F~d~rale de Lausanne (EPFL). Generally, the first step towards procuring desired physico-chemical properties in a biomaterial substrate is a chemical modification of the surface. As pointed out by B. Gupta and N. Anjum from the Indian Institute of Technology (IIT), plasma- and radiation-induced grafting treatments are widely used since they have the particular advantage that they result in highly pure, sterile and versatile surfaces. The sterilisation of implantable devices is a subject of great concern for the medical industry. Since ionising radiation is preferentially used for this purpose, attention must be paid to possible effects on the structural and mechanical properties of polymers (through chain scission or cross-linking). L.A. Pruitt from UC Berkeley has reviewed the specific behaviour of the different medical polymer classes to g- and high-energy electron irradiation and environmental effects. The biocidal efficiency relies on free radical formation and on the ability to reduce I)NA replication in any bacterial spore present in a medical device. The latter point, radiation effects on living cells and tissues, is the subject of the final contribution in this volume. M. Scholz from the Gesellschaft fiir Schwerio-

viii

Foreword

nenforschung (GSI) summarises the (damaging) biological effects of ion beam irradiation and the considerable differences with respect to conventional photon radiation. These studies are of particular importance for radiation protection and radiotherapy.The advantages of a tumor treatment by carbon ion beams (effectiveness, concentrated energy release, possibility to use the presence of positron emitting 10C and 11C isotopes for positron emission tomography) are also presented in a comprehensive way. I hope that the combination in a single special volume of the Advances in Polymer Science of these highly complementary contributions is particularly helpful to scientists working in this rapidly developing area. I would also like to thank all the authors for their exemplary co-operation. Lausanne, December 2002

H.H. Kausch

Advances in Polymer Science Available Electronically

For all customers with a standing order for Advances in Polymer Science we offer the electronic form via SpringerLink free of charge. Please contact your librarian who can receive a password for free access to the full articles. By registration at: http://link.springer.de/series/aps/reg_form.htm If you do not have a standing order you can nevertheless browse through the table of contents of the volumes and the abstracts of each article at: http://link.springer.de/series/aps/ http://link.springer-ny.com/series/aps/ There you will find also information about the -

Editorial Board Aims and Scope Instructions for Authors Sample Contribution

Contents

Engineering and Characterization of Polymer Surfaces for Biomedical Applications H. ]. Mathieu, Y. Chevolot, L. Ruiz-Taylor, D. L~onard . . . . . . . . . . . . . . . . . . . Plasma and Radiation-Induced Graft Modification of Polymers for Biomedical Applications B. Gupta, N. Anjum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

35

The Effects of Radiation on the Structural and Mechanical Properties of Medical Polymers L. A. Pruitt . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

63

Effects of Ion Radiation on Cells and Tissues M. Scholz . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

95

En91neer1n9and Character12at10n0f P01ymer5urface5 f0r 810med1ca1App11cat10n5 Han5 J6r9 Math1eu 1 • Yann Chev010t 2 • Laurence Ru12-7ay10r3 • D1d1er L~0nard 4 1 Mater1a151n5t1tute,1~c01eP01ytechn14ueF6d6ra1e de Lau5anne (EPFL), 1015 Lau5anne EPFL, 5w1t2er1and. E-ma11:Han5J0er9.Math1eu0)EPFL.ch 2 La60rat01re5 60emar, UMR 1931 CNR5/La60rat01re5 60emar, 5tat10n 61010914ue, 29660 R05c0ft: France. E-ma11: chev010t•56-r05c0ff.J• 3 2y0myx 1nc., 26101 Re5earch R0ad, Hayward CA 94545, U5A. E-ma11: LRu12-7ay10r•2y0myx. c0m 4 Ana1yt1ca17echn0109y, M1cr0ana1y5159r0up, 6E P1a5t1c5 Eur0pe, NL-4600 AC 8er9en 0p 200m, 7he Nether1and5. E-ma1h V017704•9epex.9e. c0m 7he app11cat10n 0f 5ynthet1c p01ymer5 1n the 9r0w1n9 f1dd 0f mater1a15 f0r med1ca1 app11cat10n515111u5trated6y examp1e5 fr0m recent w0rk at the Mater1a151n5t1tute0fthe 5w155Federa1 1n5t1tute 0f 7echn0109y 1n Lau5anne. 7he rev1ewh19h119ht5the need f0r funct10na112at10nand chem1ca1 c0ntr01 0f mater1a1 5urface5 at a m01ecu1ar/funct10na11eve1.After a 6r1ef 1ntr0duct10n 1nt0 the 5urface chem1ca1 ana1y515t0015,1.e.,X-ray Ph0t0e1ectr0n 5pectr05c0py (XP5) and 71me-0f-F119ht 5ec0ndary 10n Ma55 5pectr0metry (70F-51M5) c0m61ned w1th c0ntact an91e mea5urement5, ph05ph0ry1ch011ne610m1m1ck1n9p01ymer5 a5 wd1 a5 1mm061112at10n0f car60hydrate5 0n p01y5tyrene are pre5ented.

Keyw0rd5:P01ymer5,5urface ana1y515,Funct10na112at10n,1mm061112at10n,61yc0en91neer1n9

1

1ntr0duct10n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3

2

Meth0d5 f0r 5urface character12at10n . . . . . . . . . . . . . . . . .

3

2.1 2.1.1 2.1.2 2.2

5urface Chem1ca1 Ana1y515 . . . . . . . . . . . . . . . . . . . . . . . . X-ray Ph0t0e1ectr0n 5pectr0metry (XP5) . . . . . . . . . . . . . . . 71me-0f-F119ht 5ec0ndary 10n Ma55 5pectr0metry (70F-51M5) . . . C0ntact An91e Mea5urement5 . . . . . . . . . . . . . . . . . . . . . .

4 4 8 11

3

Ph05ph0ry1ch011ne Funct10na1 810m1m1ck1n9 P01ymer5 . . . . . .

13

4

5urface 61yc0en91neer1n9 0 f P01y5tyrene . . . . . . . . . . . . . . .

23

5

C0nc1ud1n9 Remark5 . . . . . . . . . . . . . . . . . . . . . . . . . . .

31

Reference5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

31

Advance5 1n P01ymer 5c1ence, V01. 162 • 5pr1n9er Ver1a9 8er11n He1de16er9 2003

2

H.J. Math1eu • Y. Chev010t • L. Ru12-7ay10r • D. L~0nard

L15t0f A66rev1at10n5 and 5ym6015 cA

Da e

E6 Ec1n EK h V

fA h 1A 1+A

1p 15 k Kc~ 1 L m

M n

5A 51 7 V

Vacc 2

Yt0t Y+A(M) 2

AE ~A ~+A(M)

Y 1v ~/5v

Y 51 ;t 0A

A 45

At0m1c c0ncentrat10n 0f e1ement A (at %) Da1t0n E1ectr0n char9e 81nd1n9 ener9y K1net1c ener9y C0re 1eve161nd1n9 ener9y P1anck•5 c0n5tant Fre4uency 0f 119ht 150t0p1c a6undance 0f dement A He19ht 0f 5e5511e dr0p (an91e 0f c0ntact) 1nten51ty 0f XP5 519na1 0f dement A 1nten51ty 0f p051t1ve 0r ne9at1ve 10n5 at ma55 A F1ux 0f pr1mary 10n5 F1ux 0f X-ray 50urce 1n5trumenta1 var1a61e (XP5) X-ray tran51t10n D1ameter 0f dr0p1et F119ht d15tance Ma55 Matr1x Num6er 5en51t1v1ty fact0r 0f dement A 5en51t1v1ty fact0r 0f dement 1 F119ht t1me 5peed Acce1erat10n p0tent1a1 Depth 70ta15putter y1e1d 70ta1 p051t1ve 0r ne9at1ve 10n y1e1d 0f e1ement A 1n matr1x M Char9e 0f m01ecu1e Ener9y re501ut10n W0rk funct10n 0f ana1y2er (XP5) P051t1ve 0r ne9at1ve 10n12at10n pr06a6111ty 0f e1ement A 1n matr1x M L14u1d-vap0r 1nterfac1a1ten510n 5011d-vap0r 1nterfac1a1ten510n 5011d-114u1d 1nterfac1a1ten510n 1ne1a5t1c mean free path 0f ph0t0e1ectr0n5 An91e Advanc1n9 an91e E5cape depth 0f ph0t0e1ectr0n5 Ana1y2er c0n5tant (70F-51M5)

En91neer1n9and Character12at10n0f P01ymer5urface5f0r 810med1ca1App11cat10n5

3

1 1ntr0duct10n Mater1a15 u5ed 1n 610med1ca1 dev1ce5 (50-ca11ed 610mater1a15) 5h0u1d fu1f111tw0 maj0r re4u1rement5. F1r5t, they 5h0u1d p055e55 the mechan1ca1 and phy51ca1pr0pert1e5 that a110w them t0 rep1ace fau1ty funct10n5 0f the 60dy. 5ec0nd, a5 they are 1nterfac1n9 6101091ca15y5tem5 they 5h0u1d 6e at 1ea5t 610-1nert (n0 unde51red react10n5) and, even 6etter, tr199er p051t1ve re5p0n5e5 fr0m the5e 6101091ca15y5tem5.1n the 1atter ca5e, re5p0n5e5 are ma1n1y 90verned 6y 1nterfac1a11nteract10n5,1.e., 6y the 5urface pr0pert1e5 0f the mater1a1 5uch a5 5urface ener9y, 5urface r0u9hne55, and 5urface chem1ca1 c0mp051t10n. C0n5e4uent1y, ana1yt1ca1 meth0d5 are 0f pr1mary 1mp0rtance t0 9u1de 5urface m0d1f1cat10n5 0f mater1a15 t0 1ead t0 6105pec1f1c 5urface pr0pert1e5 and a150 t0 under5tand the re1at10n5h1p 6etween 5urface chem15try/r0u9hne55/ener9y and the 6101091ca1 re5p0n5e. A1th0u9h h15t0r1ca11ymeta15 were the f1r5t610mater1a15, p01ymer5 have 9a1ned a 1ar9e app11cat10n 1n th15 f1e1d and 9reat eff0rt5 have 6een dev0ted t0 de519n p01ymer1c mater1a15 w1th the r19ht phy51ca1 and 1nterfac1a1pr0pert1e5 [ 1]. 7h15 w0rk 1ntend5 t0 111u5tratethe app11cat10n and 1mp0rtance 0f 5urface m0d1f1cat10n5 and the need 0f 5urface ana1yt1ca1 t0015 1n the f1e1d 0f p01ymer1c 610mater1a15 [2, 3]. 7he examp1e5 91ven 6e10w 5tem fr0m the w0rk 0f 5evera1 f0rmer PhD 5tudent5 and p05t-d0c5 0f 0ur 1a60rat0ry and 111u5trate h0w 5urface ana1y515and 6101091ca1 a55ay5 are u5ed 1n a c0mp1ementary manner t0 de519n 5ucce55fu11ynew 50ft 610mater1a15.7he f1r5t examp1e (5ect. 3) 5h0w5 h0w 0ne can 5ynthe512e a p01ymer wh05e 5urface pr0pert1e5 reduce n0n-5pec1f1c pr0te1n ad50rpt10n and c0n5e4uent1y unde51red 6101091ca1 react10n5.7he 5ec0nd examp1e (5ect. 4) c0pe5 w1th the 0r1ented 1mm061112at10n 0f 6101091ca11yact1ve m01ecu1e5 (car60hydrate5) at mater1a15 5urface5. 2 Meth0d5 f0r 5urface Character12at10n [4] 1n th15 f1r5tpart, 5urface ana1yt1ca1meth0d5 5uch a5 X-ray Ph0t0e1ectr0n 5pectr05c0py (XP5) and 71me-0f-F119ht 5ec0ndary 10n Ma55 5pectr0metry (70F-51M5) a5 we11 a5 c0ntact an91e mea5urement5 are 6r1ef1y 1ntr0duced. 7he f1r5t tw0 techn14ue5 91ve chem1ca1 1nf0rmat10n 0n the f1r5t m0n01ayer5 0f a 5011d 5urface wh11e the 1atter pr0v1de5 1nf0rmat10n re1ated t0 the 5urface ener9y. 1n the f0110w1n9 5ect10n, the 6a51c pr1nc1p1e 0f the5e ana1yt1ca1t0015 15 d15cu55ed a5 we11 a5 the typ1ca1 1nf0rmat10n they 91ve and the1r 11m1tat10n5.

H.J. Math1eu • Y. Chev010t • L. Ru12-7ay10r • D. L~0nard

4

50urce: ph0t0n5

10n5

detect0r

5pectra

519na1: e1ectr0n5 10n5 ana1y2er

1

1n-depth pmf1Je5

1ma9e5

F19.1.Pr1nc1p1e0fXP5 and 70F-51M5 5urface ana1y515

2.1 Chem1ca15urface Ana1y515 Chem1ca1 ana1y515 0f 5urface5 and 1n part1cu1ar 0f p01ymer5 15 made p055161e 6y pr061n9 w1th ph0t0n5 (50ft X-ray5) 0r 10n5 [5, 6]. 7he pr1nc1p1e 0f chem1ca1 5urface ana1y515 15 111u5trated 5chemat1ca11y 1n F19.1. A pr1mary 50urce 15 d1rected t0ward5 the 5urface 0f a 5011d 5amp1e and the 5pectr0meter mea5ure5 pr0pert1e5 0f em1tted part1c1e5. 7he em1tted 5ec0ndary part1c1e5 (e1ectr0n5 0r 10n5) carry 1nf0rmat10n 0n the c0mp051t10n 0f the t0p-5urface and under1y1n91ayer5.1n add1t10n, the 1ma91n9 capa6111t1e5 make 1t p055161e 1n certa1n ca5e5 t0 1dent1fy heter09ene1ty 1n 5urface chem1ca1 c0mp051t10n. A150, the num6er 0f detected part1c1e5 can 6e u5ed f0r (5em1-)4uant1f1cat10n d1rect1y fr0m the mea5ured 5pectra, 1n-depth pr0f11e5, 0r 1ma9e5. M0re prec15e1yXP5 (pr061n9 w1th ph0t0n5) and 70F-51M5 (pr061n9 w1th 10n5) a110w 0ne t0 acce55 depth5 fr0m 1 t0 10 nm. H0wever, due t0 the1r very h19h 5urface 5en51t1v1ty,the5e meth0d5 are 5u6ject t0 c0ntam1nat10n effect5 at the 5urface, re4u1r1n9 then a we11-c0ntr011ed preparat10n 0f the 5amp1e and u1tra-h19h vacuum (UHV) c0nd1t10n5 f0r ana1y515,1.e., pre55ure5 6e10w 10 6 Pa. 1n the f0110w1n9 a 5h0rt de5cr1pt10n 0f the tw0 ana1yt1ca1t0015 15pre5ented.

2.1.1

X-rayPh0t0e1ectr0n5pectr0metry(XP5) XP5 15 a techn14ue 6a5ed up0n ph0t0-e1ectr0n1c effect. Under X-ray (ph0t0n) exp05ure, e1ectr0n5 are em1tted w1th ener9y va1ue5 character15t1c 0f the e1ement5 pre5ent at the 5urface. F19ure 2 111u5trate5 the c0mp1ete ph0t0-10n12at10n pr0ce55 1nc1ud1n9 exc1tat10n and re1axat10n 5tep5. Let u5 a55ume that the pr1mary X-ray w1th ener9y hv create5 a ph0t0e1ectr0n at the c0re ener9y 1eve1EK (a). 7he E1n5te1n e4uat10n 91ve5 the re1at10n 6etween exc1-

En91neer1n9 and Character12at10n 0f P01ymer 5urface5 f0r 810med1ca1App11cat10n5

5

a) exc1tat10n

EF EV

hv

ph

~...,..,1/re1axat10n ~--~-~-~-,~ 6)

EF

e Au9er c)

L

EV EL X-ray EK

F19. 2. Pr1nc1p1e 0f the ph0t0-e1ectr0n1c effect: the exc1tat10n and re1axat10n pr0ce55e5 are 5h0wn 1nd1cat1n9 5chemat1ca11ythe d1fferent 61nd1n9 5tate5 w1th the Ferm1 ener9y (EF) a5 the reference 1eve1 ( 0 ) . 7he va1ence 6and ener9y 15 Ev f0110wed6y a d15crete 1eve10f EL and the c0re 1eve1EK; after [7]

tat10n ener9y (hv), k1net1c ener9y Ek1n 0f the em1tted ph0t0e1ectr0n and 1t5 61nd1n9 ener9y E6: E 6 = h v - Ek1 n - c~ A

(1)

where ~A 15 the w0rk funct10n 0f the ana1y2er detect0r. An XP5 5pectr0meter mea5ure5 the k1net1c ener9y Ek1n 0f a c0re ph0t0e1ectr0n. Fr0m E4. (1), E 6 15 determ1ned. 7he exc1tat10n pr0ce55 15 exp101ted t0 1dent1fy 5011d e1ement5 fr0m 11th1um (at0m1c n u m 6 e r 2=3). 7he 5en51t1v1ty 11m1t 1n XP5 15 appr0x1mate1y 0.1% 0f a m0n01ayer c0rre5p0nd1n9 t0 1015 part1c1e5/cm 2. An 111u5trat10n 15 91ven 1n F19.3, wh1ch 5h0w5 a 5urvey 5pectrum 0f p01y5tyrene (P5) after a rad10fre4uency 0xy9en p1a5ma treatment. 7yp1ca1 reference ener91e5 f0r 61nd1n9 ener9y ca116rat10n are acc0rd1n9 t0 the 150 5tandard [8]: Au 4f7/2 84.0 eV C 1 5 285.0 eV 1n F19.3, 0ne 065erve5 the c0re 1eve1 tran51t10n5 0fC15 and 015 a5 we11 a5 the Au9er tran51t10n 0f 0xy9en, 0 K v v. 1ndeed, the ph0t0em15510n pr0ce55 15 f0110wed 6y a re1axat10n pr0ce55 e1ther (6) 0r (c) a5 5h0wn 1n F19.2.1n the pr0ce55 (c) a th1rd e1ec-

6

H.J. Math1eu • Y. Chev010t • L. Ru12-7ay10r • D. L60nard

F19.3. XP5 5urvey 5pectrum 0f a rad10fre4uency 0xy9en p1a5ma treated p01y5tyrene (P5) 06ta1ned w1th m0n0chr0mat1c A1pr1mary rad1at10n. 7he 1nten51ty 1 (cp5) 155h0wn a5 a funct10n 0f 61nd1n9 ener9y (eV)

tr0n ca11ed the Au9er e1ectr0n 15 em1tted after a tran51t10n 0f an e1ectr0n fr0m a 10wer 1eve1 (f0r examp1e the va1ence 6and 1eve1 Ev) t0 the c0re 1eve1 E110 ° [27]. H0wever, 1n many pract1ca1 ca5e5 the exper1menta11y 065erved c0ntact an91e 0f a 91ven 5y5tem 15 n0t un14ue1y determ1ned 6y the 5urface ten510n5 0f the 5011d and

9 6 . 0 0 9 Da

0

30

-N

0

C4H2N02

a >,

m

20

-

-

=

6900

Am 0a

504 95.952 Da

0 •

.1

95,8

95,9

96,0

96.1

96,2

m/2

F19.7.71me-0f-f119ht ma55 5pectra 0f ne9at1ve 10n5 0f C4H2N02 at 96.009 Da wh1ch 15c1ear1y 5eparated fr0m 504 at 95.952 Da thank5 t0 the ma55 re501ut10n 0 f m / A m 6900

12

H.J. Math1eu • Y. Chev010t • L. Ru12-7ay10r • D. L~0nard

vap0r

%,

1

%

501[d

F19. 8. E4u1116r1um5e5511edr0p 5y5tem;Y1v15the 114u1d-vap0r,Y5vthe 5011d-vap0r,and Y51the 5011d-114u1d1nterfac1a1ten510n,re5pect1ve1yand e the mea5ured an91ew1th re5pect t0 the 5urface

114u1d, 6ut a150 6y 0ther parameter5 5uch a5 chem15try, 1nh0m09ene1ty, r0u9hne55, 5urface def0rmat10n, 5urface re0r9an12at10n, and chem1ca1 c0ntam1nat10n [28, 29]. 7he current under5tand1n9 0f the dr0p 512e dependence 0f c0ntact an91e5 15 d15cu55ed 1n a recent rev1ew 6y D. L1 [29]. 5urface5 are c1a551f1ed1nt0 h19h- and 10w-ener9y 5urface5 re9ard1n9 the1r 1nterfac1a1 pr0pert1e5. F0r h19h-ener9y 5urface5 ad50rpt10n 0ccur5 ea511y,f0r 10w-ener9y 5urface5 n0t. L14u1d5 and 50ft 0r9an1c 5011d5 5uch a5 p01ymer5 exh161t 5urface ener91e5 6e10w 100 mN/m, wh11e f0r hard 5011d5 11ke meta15 1t 15 ar0und 500-5000 mN/m. A h19h1y water- and 011 repe11ent 5urface exh161t5 a very 5ma11 cr1t1ca15urface ener9y a5 def1ned 6y 215man [30]. 6enera11y, 5urface ener9y decrea5e5 w1th 1ncrea51n9 temperature and am61ent pre55ure and r15e5w1th 1ncrea51n9 5a1t c0ncentrat10n. A 5ma11 c0ntact an91e re5u1t5 f0r wetta61e 5urface5,1f the 1nterfac1a1 ener9y 155ma11er that the 5urface ener9y 0f the pure mater1a1 at the 1nterface t0 a1r 0r vacuum. K0vat5 et a1. carr1ed 0ut 5u65tant1a1 exper1menta1 w0rk 0n c0ntact an91e5 and 5urface ener9y [31-35]. D1fferent an91e mea5ur1n9 meth0d5 were c0mpared and 5urface ten510n5 0f 83 0r9an1c 114u1d5determ1ned. 7he 1mp0rtance 0f a re11a61ereference 5urface app1y1n9 the 215man c0ncept 15 d15cu55ed 1n a the0ret1ca1 c0ntr16ut10n 6y 5wa1n and L1p0w5ky [26] pre5ent1n9 a 9enera1 f0rm 0f the Y0un9 e4uat10n. Rev1ew5 0f the cr1t1ca15urface ener9y determ1nat10n are f0und e15ewhere [36-38]. 7he 1nf1uence 0f t0p09raphy 0n wetta6111ty wa5 d15cu55ed recent1y 6y 0 n e r and McCarthy [39]. 7he hydr0ph061c1ty 0f a water repe11ent 5urface 15 d15cu55ed. 1n 5uch a ca5e the 5tat1c c0ntact an91e 15 1rre1evant, and the dynam1c wetta6111ty ha5 t0 6e addre55ed 6y mea5ur1n9 the hy5tere515, 1.e., the d1fference 6etween advanc1n9 and reced1n9 an91e. 7he 1nf1uence 0f r0u9hne55 0f u1trahydr0ph061c p01ymer 5urface5 (p01ypr0py1ene and p01y(tetraf1u0r0ethy1ene) (P7FE)) exp05ed t0 a rad10fre4uency-p1a5ma wa5 d15cu55ed e15ewhere [40] u51n9 XP5 and At0m1c F0rce M1cr05c0py t0 determ1ne 512e5ca1e and t0p0109y 0f the r0u9hne55.7he1r m05t hydr0ph061c 5urface5 exh161ted advanc1n9 (A) and reced1n9 (R) c0ntact an91e5 0f0 A and 0R=172 ° and 169 °, re5pect1ve1y.

En91neer1n9and Character12at10n0f P01ymer5urface5f0r 810med1ca1App11cat10n5

13

F19.9. C0ntact an91e ca1ctf1at10n;after [43]

C0ntact an91e mea5urement5 0f the advanc1n9 0r reced1n9 an91e can 6e perf0rmed under a m1cr05c0pe e4u1pped w1th a CCD camera and a 90n10meter determ1n1n9 the 510pe 0f the dr0p1et 0f a 91ven v01ume 0f u1trapure water (= 1015 Mf2cm). 7he wetta6111tyrep0rted 1n 5ect. 3 0f th15 rev1ew wa5 eva1uated 6y a c0ntact an91e meth0d u51n9 the 5e5511edr0p te5t 6a5ed 0n the 5em1-emp1r1ca1 meth0d pr0p05ed 6y the 11terature [41, 42]. 7he pur1ty 0fthe wett1n9 a9ent wa5 ver1f1ed 6y mea5ur1n9 the 114u1d 5urface ten510n 5v u51n9 the W11he1my techn14ue [28] (p1at1num p1ate, K5V 519ma 70 W11he1my 6a1ance) and c0mpar1n9 the 06ta1ned va1ue w1th the 11terature (y5v=78.8 mJ/m 2) [28, 43]. 7he he19ht and the c0ntact d1ameter 1 0f a 1-91 dr0p 0f de10n15ed water (9rade nan0pure m1111Q, 17 Mf2) were determ1ned after dep051t1n9 the dr0p and tak1n9 a p1cture w1th a CCD camera [28 ]. 7he advanc1n9 an91e 0 wa5 ca1cu1ated u51n9 the f0110w1n9e4uat10n [43]:

0A

= 2arctan 2

(10)

He19ht h and d1ameter 1 are 111u5trated 1n F19.9.7hey were determ1ned after dep051t10n 0fthe dr0p and tak1n9 a CCD p1cture. 7he pur1ty 0fthe wett1n9 a9ent wa5 ver1f1ed 6y mea5ur1n9 the 114u1d 5urface ten510n Y5v u51n9 the W11he1mytechn14ue (p1at1num p1ate, K5V 519ma 70 W11he1my6a1ance) and c0mpar1n9 the 06ta1ned va1ue w1th the 11terature (y5v=78.8 mJ/m2) [28, 43].

3 Ph05ph0ry1ch011ne Funct10na1 810m1m1ck1n9 P01ymer5 7h15 5ect10n 111u5trate5 re5u1t5 06ta1ned 1n 0ur 1a60rat0ry 1n the c0ntext 0f the de519n and c0ntr01 0f the 5urface pr0pert1e5 0f p01ymer5 u5ed a5 610mater1a15 [43]. 1ndeed, 1nteract10n5 6etween 610mater1a15 and t155ue5 0ccur v1a a 1ayer 0f pr0te1n5 ad50r6ed at the 5urface 0f any 1mp1ant [44]. 5uch pr0te1n ad50rpt10n 15the 1mme-

14

H.J. Math1eu • Y. Chev010t • L. Ru12-7ay10r • D. L60nard a) PCPUR

0

0

y

w

0•

2

6) P(MMA:MA:APC)

0Me

0Me

0.. ~

A 0

11

.-P-,~ A 1 0 0

/

v

..N-•

F19. 10a,6. 5chemat1c 5tructure5 0f the PC c0p01ymer 5ynthe512ed: a PCPUR; 6 P(MMA:MA:APC); after [56, 58]

d1ate event 0ccurr1n9 0n 1t5 f1r5t c0ntact w1th 6101091ca1 f1u1d5and t155ue5 [3]. 0 n e maj0r re5tr1ct10n 0f p01ymer5 15 the1r tendency t0 exh161t thr0m609en1c pr0pert1e5. 7he re5p0n5e 0f 610m01ecu1e5 and ce11mem6rane5 15 determ1ned 6y many fact0r5, 50me 0f wh1ch are the chem1ca1 c0mp051t10n and c0nf0rmat10n 0fthe m01ecu1e5, the 5urface ener9y, and t0p09raphy 0f the t0p 5urface 1ayer5 wh1ch are 1n c0ntact w1th 6101091ca15y5tem5, 1.e., 60dy f1u1d5 and ce115 [45]. 7he w0rk 111u5trated here c0n515ted 1n de519n1n9 new p01ymer5 w1th funct10na1 pr0pert1e5 capa61e 0f pr0m0t1n9 the attachment 0f 5pec1f1c ce115.7he f1r5t 5tep c0n515ted 1n a p01ymer 5y5tem wh1ch 5urface 1nh161t5 n0n-5pec1f1c ce11attachment. 7h15 5trate9y 15 6a5ed 0n the 1nc0rp0rat10n 0f ce11 mem6rane c0n5t1tuent5 5uch a5 ph05ph0ry1ch011ne (PC) 0r ph05ph011p1d ana109ue5 1nt0 p01ymer5 [46-51]. 51nce p01yurethane5 have trad1t10na11y pr0ved t0 6e rea50na61y 610- and hem0c0mpat161e mater1a15 and have theref0re 6een w1de1y u5ed f0r 610med1ca1 app11cat10n5 5uch a5 va5cu1ar pr05the515, art1f1c1a1 0r9an5, 6100d c0ntact1n9 dev1ce5, per1phera1 nerve repa1r, 0r 0ther pr05thet1c dev1ce5 [52], 0ur f1r5t PC c0p01ymer 5y5tem5 were 1n1t1a11y6a5ed 0n the p01yurethane chem15try. We had ear11er dem0n5trated that the pre5ence 0f PC 9r0up5 1n p01y(urethane) 5tr0n91y reduce5 ce11attachment at the 5urface even 1n pr0te1n enr1ched med1a [53] and w0rk fr0m C00per and c0w0rker5 [54, 55] a150 5h0wed that ph05ph0ry1ch011ne c0nta1n1n9 p01yurethane 11m1ted neutr0ph11 and 6acter1a1 adhe510n. 7w0 c0p01ymer5, PCPUR189 and PCPUR167, were 5ynthe512ed w1th d1fferent c0ncentrat10n 0f PC m01et1e5 [56]. 7he f1na1 PC c0ncentrat10n 1n the 6u1k 0fthe c0p01ymer5 wa5 3.4 m01% and 4.3 m01% f0r the PCPUR189 and PCPUR167, re5pect1ve1y. 5chemat1c5 0f 5tructure 0f the ph05ph0ry1ch011ne c0nta1n1n9 p01yurethane (PCPUR) c0p01ymer5 5ynthe512ed 15 91ven 1n F19. 10. 7he 5ec0nd c0p01ymer 5y5tem wa5 ch05en 6ecau5e 0f the h19her 5ynthet1c f1ex16111ty 0ffered 6y acry1ate chem15try. 0 u r ch01ce wa5 d1rected t0ward5 an acry11c

En91neer1n9and Character12at10n0f P01ymer 5urface5 f0r 810med1ca1/1.pp11cat10n5

15

terp01ymer 5y5tem, w1th methy1 methacry1ate (MMA) and methy1 acry1ate (MA) a5 pr1nc1pa1 c0mp0nent5.7he purp05e wa5 t0 ena61e the adaptat10n 0fthe matr1x mechan1ca1 pr0pert1e5 6y adju5t1n9 the 91a55tran51t10n temperature 0f the 5y5tem [57]. 2-Acry10y10xyethy1ph05ph0ry1ch011ne (APC) wa5 5ynthe512ed and added t0 MMA and MA thr0u9h c0p01ymer12at10n t0 c0ntr01 the 5urface pr0pert1e5 0f the P(MMA:MA:APC) terp01ymer w1th re5pect t0 ce11 attachment [58]. 7he f1na1 PC c0ncentrat10n 1n the 6u1k 0f the P(MMA:MA:APC) terp01ymer wa5 1.7 m01%. A 5chemat1c repre5entat10n 0f the 5tructure 0f the terp01ymer 15 91ven 1n F19. 10. A maj0r part 0fthe5e pr0ject5 wa5 a150 ded1cated t0 under5tand1n9 the 6u1k and 501ut10n 5tructura1 0r9an12at10n 0f 5uch p01ymer5 and here we w0u1d 11ket0 refer the reader t0 appr0pr1ate 11terature [56, 58]. Wh11e 1t wa5 5h0wn that the amph1ph11e nature 0f the terp01ymer 5y5tem, and 1n part1cu1ar the ph05ph0ry1ch011ne (PC) 9r0up5, p1ayed an 1mp0rtant r01e 1n the 5tructure 0r9an12at10n and m01ecu1ar m06111ty 0fthe c0p01ymer5, the re5u1t5 d15p1ayed 1n the pre5ent d15cu5510n f0cu5 0n h0w the pre5ence 0fthe5e PC 9r0up5 1mpacted 0n the 5urface pr0pert1e5 0fthe c0p01ymer 5ynthe512ed. W1th th15 a1m 1n m1nd, 5urface ana1yt1ca1techn14ue5 5uch a5 XP5 and 70F-51M5 were u5ed and c0mp1emented w1th c0ntact an91e5 and 6101091ca1 1n-v1tr0 a55ay5t0 character12e the dynam1c5 0f the c0p01ymer5 5urface and a55e55 the extent 0f the re515tance t0 the n0n-5pec1f1c attachment 0f ce1150n 5amp1e5 c0ated w1th the PC c0p01ymer5 (f0r exper1menta1 deta115, refer t0 [56, 58]). 70F-51M5 ana1y5150f the 2-acry10y10xyethy1 ph05ph0ry1ch011ne (APC) m0n0mer 1ed t0 the typ1ca1 p051t1ve fra9mentat10n pattern 0f the ph05ph0ry1ch011ne 9r0up 1n a9reement w1th 11terature [59, 60]. F19ure 11a 111u5trate5 the h19h re1at1ve 1nten51ty 0f 50me 0f the5e typ1ca1 p051t1ve fra9ment5 5uch a5 C5H13N+03P (166 Da) and C5H15N+04P (184 Da). A m0re exten51ve 115t0fthe maj0r p051t1ve 10n-fra9ment5 detected 15 f0und e15ewhere [58]. F19ure 116 pre5ent5 the 5ame ma55 ran9e 0fthe p051t1ve 51M5 5pectrum 06ta1ned f0r the P(MMA:MA:APC) terp01ymer. N0ne 0f the typ1ca1 fra9ment5 0f the PC 9r0up can 6e 1dent1f1edde5p1te the h19h 5urface 5en51t1v1ty0f the techn14ue. 1n c0ntra5t, character15t1c fra9ment5 fr0m P(MMA:MA) matr1x were 065erved 1n a9reement w1th the 11terature [61], 5uch a5 C 8 H 9 0 3 + (153 Da) a5 we11 a5 C 2 H 3 0 2 + (59 Da), C4H50 + (69 Da), and C5H902 + (101 Da) (n0t d15p1ayed1n F19. 116). Ne9at1ve 10n5 5pectra c0nf1rmed the5e re5u1t5.1ndeed, a1th0u9h the P0 3 fra9ment c0u1d 6e detected, 1t5 1nten51tywa5 t00 10w t0 c0n51der th15 a5 ev1dence 0f PC pre5ence. 1n c0ntra5t, 1nve5t19at10n5 0f PCPUR p01ymer5 u51n9 70F-51M5 5h0w that 60th p01ymer5 exh161t 51m11arp051t1ve and ne9at1ve m0de ma55 5pectra. 1n th15 ca5e, maj0r 5ec0ndary 10n5 character15t1c 0fthe PC p01ar head 9r0up were 065erved (P0 3 (79 Da), C5H12N+ (86 Da), C5H13N02 P+ (150 Da), C5H13N03 P+ (166 Da), and C5H15N04P + (184 Da) a5 5h0wn 1n F19.12a,6. Furtherm0re, the character15t1c fra9ment 0f 6PC c0nta1n1n9 c0at1n95, C8H19N04 P+ (224D), wa5 a150 detected (data n0t 5h0wn). 7he c0mpar150n 0f the

H.J. Math1eu • Y. Chev010t • L. Ru12-7ay10r • D. L~0nard

16

184

11~~

[777]

166

1~ ~ :1~ ~,~1

~

:1 5 •1 C

1111

150

0H

1

160

170

180

o Zo

190

200

6) P(MMA-MA-APC)

•1•1

[

....

150

160

170

180

190

200

m/2 [a.m.u.]

F19.11a,6. C0mpar150n 6etween the p051t1ve 70F-51M5 ma55 5pectra 0fthe APC: a m0n0mer; 6 terp01ymer 1n the 150 200 Da ma55 ran9e; after [58]

3.5 104 X 20

"~

0

3,5 104

.....

0

20

40

60

"~ 2,

m 0

83

100

120

J...~.... 2.. 2 . . . . . . . . . .

140

160

180

x 20

0

20

40

60

80

200 D)

100

120

140

...... ~ 160

180

200

F19. 12a,6. C0mpar150n 0f the p051t1ve m0de 70F-51M5 5pectra 0f: a PC-PUR189; 6 PCPUR1671n the ma55 ran9e 0 200 Da, after [56]; * den0te5 the p051t10n 0fthe character15t1c PC fra9ment5

p051t1ve m 0 d e 70F-51M5 5pectra 5h0w5, h0wever, that re1at1ve n0rma112ed 1nten51t1e5 0f the character15t1c PC fra9ment5 are h19her 6y appr0x1mate1y 50% f0r PCPUR167 c0mpared t0 PCPUR189. 5tud1e5 re9ard1n9 the c0nf0rmat10n 0f1ec1th1n5 have a110wed the determ1nat10n 0 f t h e 512e 0 f t h e ph05ph0ry1ch011ne p01ar 9r0up. 7h15 d1men510n der1ved fr0m X-

En91neer1n9 and Character12at10n 0f P01ymer 5urface5 f0r 810med1ca1App11cat10n5

17

1a61e 1. AR-XP5 5urface e1ementa1 c0ncentrat10n5 0f PCPUR and P(MMA:MA:APC) c0p01y-

mer5. C0mpar150n 6etween tw0 em15510nan91e5 0f20 and 80 0 w1th re5pect t0 the 5amp1e 5urface, c0rre5p0nd1n9 t0 an 1nf0rmat10n depth 0f 3 4 nm and 8 11 nm, re5pect1ve1y;c0mp11ed after [56, 58] Em15510n an91e (1nf0rmat10n depth)

C [at%]

0 [at%]

N [at%]

P [at%]

PCPUR189

67.1+0.5 66.1+0.0 66.7+0.6 65.9+0.8 70.0+0.6 70.0+0.0

21.4+0.8 21.6+0.3 21.6+0.7 21.8+0.7 29.8+0.6 29.4+0.0

11.5+0.5 11.7+0.2 11.4+0.3 11.7+0.3 0.0 0.3+0.06

0.3+0.09 0.6+0.06 0.6+0.06 0.8+0.06 0.2+0.02 0.3+0.03

PCPUR167 P(MMA:MA:APC)

20 0 (3 80 0 (8 20 0 (3 80 0 (8 20 0 (3 80 0 (8

4 nm) 11 nm) 4 nm) 11 nm) 4 nm) 11 nm)

ray d1ffract10n 5tud1e5 15 11 A f0r 60th the m0n0hydrated 0r fu11y hydrated 1ec1th1n5 [62] and 151n a9reement w1th the 12 A 06ta1ned w1th 5pace-f1111n9 m0de15 f0r a fu11y extended PC 9r0up para11e1 t0 the fatty ac1d cha1n5 and w1th the 2w1tter10n 1n the 9auche c0nf0rmat10n a60ut the 0 - C - C - N 60nd5 [63]. Hence, the typ1ca1 fra9ment5 0f the ph05ph0ry1ch011ne 9r0up5 5h0u1d 6e detecta61e 1f they were pre5ent at the upperm05t 5urface 0f the P(MMA:MA:APC) terp01ymer. P055161e matr1x effect5 have a1ready 6een rep0rted 1n 0r9an1c 5y5tem5 [64, 65]. A1th0u9h they may affect the em15510n pr06a6111t1e5 0f typ1ca1 PC 5ec0ndary 10n5, 1t 15 very un11ke1y that they 5h0u1d 1nh161t c0mp1ete1y the em15510n 0f a11 the PC fra9ment5. 7he5e 51M5 065ervat10n5 theref0re 5u99e5t that under the U H V c0nd1t10n5 re4u1red f0r the ana1y515, the extreme 5urface 0f the P(MMA:MA:APC) terp01ymer 15 dep1eted 1n PC 9r0up5.7h15 6ury1n9 effect can d1rect1y 6e under5t00d 6y the de51re 0 f t h e 5y5tem t0 re0r9an12e 50 a5 t0 m1n1m12e 5urface ener9y 1n U H V env1r0nment. XP5 ana1y5e5 were perf0rmed 0n a11 c0p01ymer5.7he at0m1c c0ncentrat10n5 0f car60n (C15), 0xy9en (015), n1tr09en (N15), and ph05ph0ru5 (P2p) were c0mpared 6etween the tw0 depth5 0f 3-4 n m and 8-11 n m and are rep0rted 1n 7a61e 1. C0ntra5t1n9 w1th 70F-51M5 ana1y515, n1tr09en and ph05ph0ru5 were detected 0n the P(MMA:MA:APC), a1th0u9h 1n the ca5e 0f n1tr09en we were c105e t0 the detect10n 11m1t. A5 1t can a150 6e 5een fr0m the h19h re501ut10n e1ementa1 5can5 rep0rted 1n F19. 13a,6, the n1tr09en and ph05ph0ru5 at0m1c c0ncentrat10n5 mea5ured are very 10w; f0r an em15510n an91e 0f20 ° n0 n1tr09en 15 even detected wherea5 the ph05ph0ru5 c0ncentrat10n 15 a60ut 0.2 at%. 7h15 can 6e under5t00d 6y c0n51der1n9 the d1fference 0f e1ectr0n 1ne1a5t1c mean free path5 (1mfp) 6etween 60th e1ement5.1ndeed, ca1cu1at10n5 6a5ed 0n the e5t1mat10n 0 f t h e 1mfp made 6y 7anuma et a1. [66] f0r P M M A a5 we11 a5 0n the re1at10n der1ved 6y 5eah and Dench [67] f0r the 1mfp 0f 0r9an1c c0mp0und5 a110w the e5t1mat10n 0f the e5cape depth 0f the XP5 1nf0rmat10n. 80th appr0ache5 91ve 51m11ar re5u1t5.1n the ca5e 0f n1tr09en, the 1nf0rmat10n depth 15 appr0x1mate1y 3 n m and 9 n m wherea5 f0r ph05ph0ru5 1t

18

H.J. Math1eu • Y. Chev010t • L. Ru12-7ay10r • D. L60nard

E5cape depth 3 nm E 5 c a p e d e p t ~ 9 ~m

2

410

405

400

81ND1N6 ENER6Y

- -

395

[eV]

6) P2p

E5capedepth 4 nm E5capedepth 11 nm

2

1•••1

. . . . . . . . .

140

1 . . . . . . . . .

135

1 . . . . .

1

130

81ND1N6 ENER6Y [eV]

F19.13a,6. H19h-re501ut10n e1ementa15can5 a5 a funct10n 0f depth 0f1 a the n1tr09en N15; 6 the ph05ph0r0u5 P2p 0fthe P(MMA-MA-APC) c0p01ymer; after [58]

ran9e5 fr0m 4 nm t0 11 nm f0r the 20 ° and 80 ° em15510n an91e5, re5pect1ve1y. A5 the 1nf0rmat10n depth 15 au9mented, an 1ncrea5e 1n the n1tr09en (fr0m 0 t0 0.3 at%) and ph05ph0ru5 (fr0m 0.2 t0 0.3 at%) at0m1c c0ncentrat10n5 15 n0t1cea61e. 51m11ar c0mment5 can 6e made c0ncern1n9 the PCPUR c0p01ymer5, f0r wh1ch e1ementa1 c0ncentrat10n5 are c0mpara61e f0r 60th c0p01ymer5 at 60th em15510n an91e5, except 1n the ca5e 0f ph05ph0ru5.1ndeed, a1th0u9h ph05ph0ru5 c0ncentrat10n5 detected are very 10w, they are 519n1f1cant1y d1fferent (0ut51de 0f the exper1menta1 dev1at10n) and 5h0w that the c0ncentrat10n 15 h19her 1n PCPUR167 (7a61e 1) 1n a9reement w1th the 70F-51M5 re5u1t5 de5cr16ed ear11er. M0re0ver, 1t can 6e 5een that the ph05ph0ru5 P2p ph0t0e1ectr0n 1nten51ty (and c0n5e4uent1y

En91neer1n9and Character12at10n0f P01ymer5urface5f0r 810med1ca1App11cat10n5

19

the ph05ph0ru5 at0m1c c0ncentrat10n) a150 1ncrea5e5 w1th the depth ana1y2ed f0r the5e PCPUR c0p01ymer5. 7h15 5u99e5t5 that under UHV c0nd1t10n5, f0r 60th c0p01ymer 5y5tem5 (acry1ate5 0r p01yurethane5), there 15 an 1ncrea51n9 c0ncentrat10n 9rad1ent 0f the ph05ph0ry1ch011ne 9r0up5 fr0m the 5urface t0 the 6u1k 0f the p01ymer. 7he c0p01ymer 5y5tem tend5 t0 10wer 1t5 1nterfac1a1 free ener9y 6y 6ury1n9 the PC 9r0up underneath the extreme 5urface. 1n-v1tr0 a55ay5 were perf0rmed 1n 5erum free (5FM) and 5erum c0nta1n1n9 med1a (5CM) t0 eva1uate the ce11 attachment pr0pert1e5 0n 60th PC-c0nta1n1n9 and PC-free c0p01ymer5 t09ether w1th 510 2 a5 reference [56, 58]. Re5u1t5 06ta1ned after 4 h 0f 1ncu6at10n (F195. 14 and 15) 5h0w that the ce11 attachment and d1fferent1at10n 1eve15 0n the PC c0nta1n1n9 c0p01ymer5 were 5tr0n91y reduced 1n 60th med1a c0mpared t0 PC free 5y5tem and the 510 2 reference. Hence, a 5ma11 c0ncentrat10n 0f PC 9r0up5 (-1.7 m01% f0r the P(MMA:MA:APC) and -3.4m01% f0r PCPUR189) 15 a1ready eff1c1ent 1n reduc1n9 the n0n-5pec1f1c attachment 0f ce1156y r0u9h1y 70% f0r 60th med1a. Ce11 attachment 15 even further reduced a5 the PC c0ntent 0f the c0p01ymer 1ncrea5e5 (-4.3 m01% f0r PCPUR167), 51nce a 90% decrea5e 15 06ta1ned f0r PCPUR167 1n 60th med1a when c0mpared t0 510 2. Exten510n 0f the cu1ture t1me up t0, re5pect1ve1y, three day5 f0r the P(MMA:MA:APC) c0p01ymer and f0ur day5 f0r the PCPUR c0p01ymer5, 5h0wed n0 ev01ut10n 1n the ce11 attachment pr0pert1e5 0n the PC c0nta1n1n9 5urface5, a5 0pp05ed t0 the PC-free 5urface5 (510 2 reference a5 we11 a5 P(MMA:MA) p01ymer). 1ndeed, after 72 h 1n 5CM, a 1ar9e p0pu1at10n 0f ce115were attach1n9 and d1fferent1at1n9 0n P(MMA:MA) a5 can 6e 5een fr0m F19. 16a. 1n c0ntra5t, 0n the

140 120

[] [] []

5102 P(MMA:MA) P(MMA:MA:APC)

100

F~

80 60

8 9 ~u

40 20 0 5FM

5CM

F19.14. C0mpar150n 0fthe ce11attachment 1eve1after 4 h 1ncu6at10n, 0n the APC free and the APC c0nta1n1n9 c0p01ymer5 a5 a funct10n 0f t1me 1n 5erum free (5FM) and 5erum c0nta1n1n9 (5CM) med1a; after [58]

20

H.J. Math1eu • Y. Chev010t • L. Ru12-7ay10r • D. L~0nard

5102

2°° 1

PC-PUR189

~

PC-PUR167

150 1 1

J 1 1 100

50

0~ 5FM

5CM

F19.15. C0mpar150n 0f the ceH attachment 1eve1 0n the 5102 reference, PC-PUR189 and PC-

PUR167 after 4 h 1n 5FM and 5CM ( ~rp 10 6191cm2) c0u1d 6e 1mm061112ed 0n the 5urface (F19. 17). 7he wa5h1n9 0f the d1p-c0ated 5urface, h0wever, 1ead5 t0 a1m05t 50% 1055 1n c011a9en. 7h15 ar15e5 due t0 the 1005e1y60und c011a9en 6e1n9 wa5hed away. Ur1nary 61adder rec0n5truct10n 150ne 0f the m05t recent 1nn0vat10n5 1n the d0ma1n 0f the t155ue en91neer1n9.7he 61adder ur0the11a1 ce115 and 5m00th mu5c1e ce115 may 6e 5eeded 0nt0 a p01ymer 5upp0rt, cu1tured 1n v1tr0, and expanded t0 a re4u1red 512e [82-86]. Here text11e mater1a15 0ffer 1nn0vat1ve 5urface5 f0r 61adder c0n5truct10n [83]. Kn1tted 5caff01d5 0ut 0f 60th the 6105ta61e 5caff01d5 - 5uch a5 p01ye5ter - and the 610de9rada61e 0ne5 - 5uch a5 p01y91yc011cac1d - may 6e u5ed f0r the ce115eed1n9.7he c011a9en 1mm061112ed PE7 5urface5 pr0v1de exce11ent 1nterface f0r the 5eed1n9 0f ur0the11a1 ce115and 5m00th mu5c1e ce115.7he5e ce115adhere and 9r0w we11 0n the c011a9en 1mm061112ed 5urface5 (F19.18). 7he kn1tted PE7 5tructure5 0ffer a 6etter 51mu1ated matr1x f0r 61adder c0n5truct10n. 7he advanta9e 15that they e10n9ate under 5tre55.7he 1ar9e hy5tere515 0f the kn1tted 5tructure5 15 n0t 0n1y due t0 the hy5tere515 0f the yarn 1t5e1f 6ut ma1n1y due t0 the 5tra19hten1n9 0f the 100p5 and the p05516111ty0f the m0vement 0f the yarn re1at1ve

P1a5ma and Rad1at10n-1nduced 6raft M0d1f1cat10n 0f P01ymer5 f0r 810med1ca1App11cat10n5

57

20

0

8ef0rewa5h1n9 ]

u9

~

5 0 5

1 10

1 15

1 20

25

6raft Den51ty(~9/cm 2)

F19.17. Var1at10n 0f V1tr09en c0ntent w1th the 9raft den51ty 011 p1a5ma 9rafted PE7-9-PAA f1hn5 [59]

F19.18.5m00th mu5c1e 9r0wth 0n V1tr09en 1mm061112edPE7-9-PAA f11m (5 6t9/cm2) PAA [59]

t0 the 1nd1v1dua1100p5.7he 1mp0rtant a5pect 0f kn1tted 5tructure5 15 that the def0rmat10n 15 near1y rever5161e. Hence, the 9r0wth 0f ur0the11a1 ce115and 5m00th mu5c1e ce1150n the kn1tted 5urface5 may 1ead t0 a m0re appr0pr1ate p1atf0rm f0r the ce115eed1n9 [84-85]. 810m1met1c 5urface5 may 6e pr0duced 6y UV 9raft m0d1f1cat10n 0f PE 5urface w1th v1ny1meth0xy511ane and 5u65e4uent hydr01y515 [86].

58

8 . 6 u p t a • N. Anjum

7he m0d1f1ed 5urface, a5 1nve5t19ated 1n a 51mu1ated 60dy f1u1d, 5h0wed a den5e and h0m09ene0u5 60ne m1nera1 11ke apat1te 1ayer even 0n f16er5, wh1ch may 6e 5u65e4uent1y w0ven up 1nt0 a c0mp051te 5tructure t0 pr0duce a three-d1men510na1 5tructure ana1090u5 t0 that 0f natura1 60ne. 7here 15 an 1ncrea51n9 demand f0r 610de9rada61e p01ymer5 f0r 5caff01d preparat10n. P01y(0t-hydr0xy ac1d5) 5uch a5 p01y91yc011cac1d and p01y1act1c ac1d and the1r c0p01ymer5 0ffer the re4u1red phy51c0-chem1ca1 character15t1c5 f0r the1r funct10n a5 extra-ce11u1ar matr1x 1n t155ue en91neer1n9. 7he5e p01ymer5 may n0t nece55ar11y need a 9raft m0d1f1cat10n t0 enhance the 5urface funct10na11ty; 1n5tead 5urface hydr01y515 may 6e en0u9h f0r a funct10na112ed 5urface. 7he advanta9e 0f 5uch p01ymer5 15 that the1r de9radat10n rate may 6e ea511yc0ntr011ed 6y carefu1 c0mp051t10n 0f the c0p01ymer5.7he extra-ce11u1ar matr1x de9rade5 and 1eave5 6eh1nd an 1ntact patch 0f the t155ue at the tran5p1antat10n 51te. 7155ue5 en91neer1n9 ha5 6een 5ucce55fu11n de519n1n9 and tran5p1antat10n 0f art1f1c1a1ha1r 1nt0 human 5ku11 [36]. 7he art1f1c1a1ha1r 15 fa6r1cated fr0m p01y(ethy1ene terephtha1ate) m0n0f11ament where the t155ue c0ntact1n9 part 0f the f11ament 15 m0d1f1ed t0 make 1t 610c0mpat161e. 1n th15 pr0ce55, the m0n0f11ament 15 m0d1f1ed 6y 9raft1n9 0f acry11c ac1d u51n9 5u1ta61e 1n1t1at10n pr0ce55, 5uch a5 UV rad1at10n. 7h15 m0d1f1ed f11ament 155u65e4uent1y 1mm061112edw1th c011a9en u51n9 91utara1dehyde cr05511nker. Ce115 may 6e 1mm061112ed 0nt0 th15 m0d1f1ed 5urface f0r 5u65e4uent 1mp1antat10n 1nt0 the human 5ku11.7h15 pr0cedure 15 50 exc1t1n9 that 1t ha5 6een app11ed t0 m0re than 110,000 5ca1p5 f0r ha1r rep1acement5 w0r1d w1de. Va5cu1ar 9raft5 are a150 1mp0rtant d0ma1n5 0f t155ue en91neer1n9, a5 5h0wn 6y appr0x1mate1y 750,000 c0r0nary artery 6ypa55 9raft 5ur9er1e5.7he trad1t10na1 meth0d 0f treatment 15 t0 u5e a 6100d ve55e1 fr0m an0ther 10cat10n 1n the pat1ent (aut09raft), e.9., fr0m the 1e9.7he pr061em w1th the aut09raft pr0cedure 15 that 1t re4u1re5 mu1t1p1e 5ur9er1e5 and 1ncrea5ed r15k and c05t t0 the pat1ent. M0re0ver 30% 0f6ypa55 pat1ent51ack 5u1ta61eve55e15.7155ueen91neered 9raft5 theref0re pr0v1de a fea5161e a1ternat1ve. 7here are 5evera1 fact0r5 t0 c0n51der 1n 9raft deve10pment, 1nc1ud1n9 the permea6111ty, 51nce 1t 15a f1u1d-c0nta1n1n9 dev1ce, and the f1ex16111ty, 1t mu5t 6e read11y hand1ed and 5utured 5ecure1y 1nt0 p1ace. 8ra1ded f16er5 and kn1tted text11e5 are exce11ent mater1a15 f0r the ECM wh1ch may 6e m0d1f1ed 6y 1nc0rp0rat1n9 p01ar funct10na1 9r0up5 f0r c011a9en 1mm061112at10n where ce115 may 6e 5eeded 1n a three-d1men510na1 manner and a 9raft may 6e pr0duced.

4 C0nc1u510n P01ymer5 have deve10ped en0rm0u5 1ntere5t 1n a num6er 0f 610- and med1ca1 re1ated app11cat10n5 where phy51c0-chem1ca1 character15t1c5 0f 60th the 5urface and the 6u1k need t0 6e ta110red. 51nce the 610mater1a1 rema1n5 1n c105e c0ntact w1th the 11v1n960dy, the react10n fr0m the t155ue5 w0u1d 6e a funct10n 0f the 5urface

P1a5ma and Rad1at10n-1nduced6raft M0d1f1cat10n0f P01ymer5f0r 810med1ca1App11cat10n5

59

character15t1c5. A1m05t n0 mater1a1 can act a5 a c0mp1ete1y 610c0mpat161e 0ne. 7heref0re 1t 15 needed t0 deve10p p01ymer1c mater1a15 w1th the m1n1mum adver5e re5p0n5e fr0m the 60dy. 7he p01ymer 5urface5 need5 pr0per de519n1n9 1n term5 0f the chem1ca1 funct10na11ty 1n 5uch a way that the c0mpat16111ty 0f the 610mater1a1 w1th the 60dy 15 enhanced. 6raft p01ymer12at10n 0f 5pec1f1c m0n0mer5 0ffer5 an attract1ve r0ute t0ward5 the m0d1f1cat10n 0f p01ymer5 50 that the mater1a1 ac4u1re5 de51red pr0pert1e5 wh11e reta1n1n9 m05t 0f the 1nherent character15t1c5.7he extent 0f c0mpat16111ty, theref0re, re5t5 w1th the chem1ca1 nature 0f the m0n0mer and 1t5 c0ntent 1n the m0d1f1ed matr1x. 80th p1a5ma and h19h ener9y rad1at10n are 6e1n9 u5ed f0r the 5e1ect1ve 1ntr0duct10n 0f chem1ca1 funct10na11ty. P1a5ma-1nduced 9raft p01ymer12at10n 15 an 1nn0vat1ve way 1n term5 0f the nan0-5ca1e th1ckne55 m0d1f1cat10n 0f the 5urface. 7h15 15 an advanta9e 1n term5 0f a1m05t c0mp1ete retent10n 0f the mechan1ca1 5tren9th 0fthe 610mater1a1 after 9raft m0d1f1cat10n. 7h15 15he1pfu1 1n de519n1n9 5urface5 f0r 1nn0vat1ve area5 0f t155ue en91neer1n9 where human ce115are 5eeded 0n the nan05tructured 5urface f0r 5u65e4uent harve5t1n9 1nt0 a t155ue. 7he rad1at10n, 0n the 0ther hand, 1ead5 t0 5urface and 6u1k m0d1f1cat10n 0f the mater1a1. A5 the 9rafted c0mp0nent rema1n5 th0r0u9h1y d15tr16uted acr055 the matr1x, the wh01e matr1x 15 funct10na112ed 6ut the ten511e 5tren9th may 6e adver5e1y affected. 1t 15 1mp0rtant t0 ment10n here that the ten511e 5tren9th w1116e a funct10n 0fthe am0unt 0fthe 9rafted c0mp0nent and 1t5 c0mpat16111tyw1th the 0r191na1 matr1x. 7here 15a w1de 5pectrum 0f app11cat10n area5 0f 610mater1a15.7he area 0f t155ue en91neer1n9 ha5 further 0pened up a newer d0ma1n 0f610mater1a15 where pr0per 51mu1at10n 0f p01ymer-ce11 1nteract10n need5 t0 6e f0110wed. A5 a matter 0f fact the r01e 0f p01ymer5 a5 610mater1a1 15 5pread1n9 fa5t. Ma W m0re d0ma1n5 5h0u1d 6e c0m1n9 up 1n the next 9enerat10n 0f mater1a15 where m0re attent10n 0n the match1n9 0f the phy51ca1pr0pert1e5 w1th the chem1ca1 funct10na112at10n w1116e re4u1red. Here, pr0per weav1n9 0f the kn0w1ed9e 0f a mater1a1 5c1ent15t and a 610techn010915t w1116e re4u1red t0 up9rade the c0ncept 0f 610mater1a1 1n 1nn0vat1ve d0ma1n5. Reference5

1. W15eDL, 7rant010 DJ, Mt06e111DE, Ya52em5k1MJ, 6re55er JD, 5chwart2, ER (1995) Encyd0ped1c hand600k 0f 610mater1a15 and 610en91neer1n9. Marce1 Dekker, New Y0rk 2. Van Kampen CL (1979) J 810med Mater Re5 13:517 3. A65010m DR, 7h0m50n C, Hawth0rn LA, 21n99 W, Neumann AW (1988) J 810med Mater Re5 22:215 4. Ratner 8D, H0f1•man A5, Han50n 5R, Harker LA, Wh1f1•en JD (1979) J P01ym5c1 P01ym 5ymp 66:363 5. Van Wachem P8, 8eu9e11n97, Fe1jen J, 8antje5 A, Detmer5 JP, van Aken W6 (1985) J 810med Mater Re5 6:403 6. He1mu5MN, 61660n5 DF, J0ne5 RD (1984) J 810med Mater Re5 18:165 7. 1kadaY (1994) 810mater1a15 13:725

60 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54.

8 . 6 U p t a • N. AnjUm 8ure5 P, Huan9 Y, 0ra1E, Peppa5 NA (2001) J C0ntr01 Re1 72:25 Kamath KR, Park K (1994) JApp1 810mat 5:163 0ehr C, Mtt11er M, E1kn 8, V0hrer U (1999) 5urf C0at 7echn01 116:25 Lee JH, Park JW, Lee H8 (1991) 810mater1a15 12:443 K1ae1D, H0ffman A5, H0r6ett 7A (1995) Rad1at Phy5 Chem 46:191 6upta 8, H1160rn J, H011en5te1n C, P1ummer CJC, Xandr0p010u5 N, H0ur1et R (2000) J App1 P01ym 5c1 78:1083 Hayat U, 71n51eyAM, Ca1der MR, C1arke DJ (1992) 810mater1a15 13:801 Ward 7L, H1n0ja5a 0, 8ene51t0 RR (1982) P01ym Ph0t0chem 2:109 Yeh Y, 1r1yamaY, Mat5u2awa Y, Han50n 5R, Ya5uda H (1988) J 810med Mater Re5 22:795 K0 7, C00per 5L (1993) J App1 P01ym 5c1 47:1601 6upta 8, H1160rn J, 81550n 1, Frey P (2001) J App1 P01ym 5c1 81:2993 5harma CP, Jaya5ree 6, Najee6 PP (1987) J 810mat App1 2:205 H51ue 6, Wan9 C (1993) J P01ym 5c1Chem 31:3327 H51ue 6, Lee 5D, Wan9 CC, Chan9 PC7 (1993) J 810med 5c1 P01ym 5:205 5an0 5, Kat0 K, 1kada Y (1993) 810mater1a15 20:529 Chen H, 8e1f0rt 6 (1999) J App1 P01ym 5c1 72:1699 Lee 5, H51ue 6, Wan9 C (1994) J App1 P01ym 5c154:1279 5u2uk1M, K15h1daA, 1wata H, 1kada Y (1986) Macr0m01ectf1e5 19:1808 U16r1cht M, 8e1f0rt 6 (1996) J Mem6r 5c1 111:193 8ae J, 5e0 E, Kan9 1 (1999) 810mater1a15 20:529 Kan9 1, Kw0n 0H, Lee YM, 5un9 YK (1996) 810mater1a15 17:841 K1m EJ, Kan9 1, Jan9 MK, ParkY8 (1998) 810mater1a15 19:239 Lee JH, K0pecek J, Andrade JD (1989) J 810med Mater Re5 23:351 K0 Y9, K1m YH, Park KD, Lee HJ, Lee WK, Park HD, 500 HK, Lee 65, Ahn DJ (2001) 810mater1a15 22:2115 Fuj1m0t0 K, 1n0ue H, 1kada Y (1993) J 810med Mater Re5 27:1559 De5a1NP, Hu66e11 JA (1991) J 810med Mater Re5 25:829 60m60t2 WR, 6uan9hu1 W, 7h0ma5 AH, H0ffman A5 (1991) J 810med Mater Re5 25:1547 Kan9 1, Kw0n 0H, Lee YM, 5un9 YK (1996) 810mater1a15 17:841 Kat0 K, Y05h1111t0Y, Yamam0t0 M, 70m1ta N, Yamada 5, 1kada Y (2000) J Adhe510n 5c1 7echn01 14:635 UyamaY, 7adakar0 H, 1kadaY (1991) 810mater1a15 12:71 R1chey 7, 1wata H, 00wa5ak1 H, Uch1da E, Mat5uda 5, 1kada Y (2000) 810mater1a15 21:1057 Eckert AW, 6r66e D, R0the U (2000) 810mater1a15 21:441 Uch1da E, Uyama Y, 1kada Y (1990) J App1 P01ym 5c1 41:677 Jen MY, M1n9 CW, Y1n9 6H, Chau HC, 51n9 KL (1998) J Mem6r 5c1 138:19 2han9 F, Kan9 E7, Ne0h K6, 7an KL (2001) 810mater1a15 56:324 Chap1r0 A (1962) Rad1at10n chem15try 0fp01ymer1c 5y5tem5.W11ey1nter5c1ence Ratner 8D, H0ffman A5 (974) J App1 P01ym 5c1 18:3183 H0ffman A5, Achmer 6, Harr15 C, Kraft W 6 (1972) 7ran5 Am 50c Art1f 1ntern 0r9an5 18:10 Ka6an0v V, Kudryavt5ev VN, De9tyareva 7V, 2at1kyan LL, 8a5k0va 1R 5tarann1k0va LE (1997) Nud 1n5tr Meth0d5 Phy5 Re5 8131:291 Han DK, Je0n9 5Y, K1mYH, M1n 86, Ch0 H1 (1991) J 810med Mater Re5 25:561 8r1nkman E, P00t A, Van der D0e5 L, 8antje5 A (1990) 810mater1a15 11:200 Kw0n 0H, Nh0 YC, Park KD, K1mYH (1999) J App1 P01ym 5c1 71:631 6upta 8, 8t1ch1 FN, 5cherer 6 6 , Chap1r0 A (1994) P01ym Adv 7echn01 5:493 6upta 8, Anjum N (2000) J App1 P01ym 5c1 77:1331 5un YH, 60m60t2 WR, H0ffman A5 (1986) J 810act C0mp P01ym 1:317 6upta 8, 7ya91 PK, Ray AR, 51n9h H (1990) J Macr0m01 5c1 Chem 27:831 51n9h DK, RayAR (1994) J App1 P01ym 5c1 53:1115

P1a5ma and Rad1at10n-1nduced 6raft M0d1f1cat10n 0f P01ymer5 f0r 810med1ca1App11cat10n5

61

55. 6upta 8, Anjum N (2000) J App1 P01ym 5c177:1401 56. Park J5, K1m JH, Nh0 YC, Kw0n 0 H (1998) J App1P01ym 5c1 69:2213 57. Uch1da K, 5aka1 K, 1t0 E, Kw0n 0H, K1kuch1A, Yamat0 M, 0kan0 7 (2000) 810mater1a15 21:923 58. K1m YJ, Kan9 1, Huh MW, Y00n 5 (2000) 810mater1a15 21:121 59. 6upta 8, P1ummer C, 81550n 1, Frey P, H1160rn J (2002) 810mater1a15 23:863 60. 6upta 8, Anjum N (2002) J App1 P01ym 5c186:1118 61. Ratner 8D (1995) 8105en50r5 810dectr0n 10:797 62. Uyama Y, 7ad0kar0 H, 1kada Y (1990) J App1 P01ym 5c1 39:489 63. 70m1ta N, 7ama15, 0kaj1ma E, H1ra0 Y, 1keuch1 K, 1kada Y (1994) J App1 810mat 5:175 64. Ratner 8D, H0ffman A5, Wh1ffen JD (1978) J 810en9 2:313 65. C0hn D, H0ffman A5, Ratner 8D (1987) J App1 P01ym 5c131:1 66. Lee H8, 5h1m H5, Andrade JD (1972) Am Chem 50c P01ym Prepr1nt 13:729 67. A1exander JW, Kap1an J2, A1teme1er WA (1967) Ann 5ur9 165:192 68. 51n9h H, 7ya91 PK (1989) D1e An9ew Makr0m01 Chem1e 172:87 69. 7ya91 PK, 6upta 8, 51n9h H (1993) J Macr0m015c1 Pure App1 Chem A 30:303 70. 8ucken5ka J (1996) J App1 P01ym 5c1 61:567 71. Park J5, K1m JH, Nh0 YC, Kw0n 0 H (1998) J App1P01ym 5c1 69:2213 72. Kan9 1, Kw0n 0H, 5un9 YK, Lee YM (1997) 810mater1a15 18:1099 73. Yamata M, K0nn0 C, Ut5um1M, K1kuch1A, 0kan0 7 (2002) 810mater1a15 23:561 74. Lan9er R, Vacant1JP (1993) 5c1ence 260:920 75. 7emen0ff J5, M1k05 A6 (2000) 810mater1a15 21:431 76. M1r2adeh H, Kat6a6 AA, Kh0ra5an1 M7, 8urf0rd RP, 60r91n E, 601e5tan1A (1995) 810mater1a15 16:641 77. K15h1daA, 1wata H, 7amada Y, 1kada Y ( 1991) 810mater1a15 12:786 78. K1m 8, M00ney DJ (1998) 7187ECH 16:224 79. Lee 5, H51ue 6, Chan9 PC, Ka0 C (1996) 810mater1a15 17:1599 80. H1160rn J, Frey P 8r1t15h Pat App1 9,824,562 81. 7amada Y, 1kadaY (1994) J 810med Mater Re5 28:783 82. 6upta 8, Frey P, 81550n 1, H1160rn J (2000) P01ym Preprh1t5 4:1040 83. 8ur9 KJL (2001) 1nt1 F16re J 16:38 84. Reva9ade N (2001) M 7ech 7he515, 117 De1h1, 1nd1a 85. 81550n 1, K051nk1M, Rua1t 5, 6upta 8, H1160rn J, Wurm F (2002) 810mater1a15 23:3149 86. K1m H, May0 U, K0 K7, M1n0da M, M1yam0t0 7, Nakamure 7 (2001) 810mater1a15 22:2489 Rece1ved: Apr114th, 2002

7he Effect5 0f Rad1at10n 0n the 5tructura1 and Mechan1ca1 Pr0pert1e5 0f Med1ca1 P01ymer5 L15a A. Pru1tt Department5 0f Mechan1ca1 En91neer1n9 and 810en91neer1n9, UC 8erke1ey, 8erke1ey, CA 94720 U5A.

E-ma1h 1pru1tt•newt0n. 6erke1ey.edu

Med1ca1 p01ymer5 under90 chan9e5 1n 60th 5tructura1 and mechan1ca1pr0pert1e5 when 5u6jected t0 10n121n9rad1at10n. Certa1n c1a55e5 0f p01ymer5 are 5u5cept161e t0 cha1n 5c15510n mechan15m5wh11e0ther5 are a1teredthr0u9h cr05511nk1n9pr0ce55e5.7he5e 9enera112at10n5are c0mp11cated 6y the atm05phere 1n wh1ch the p01ymer 15exp05ed t0 the 10n121n9treatment. 8ecau5e the5e dev1ce5 mu5t 6e 5ter1112edpr10r t0 1mp1antat10nthe1r 10n9-term 5tructura1 ev01ut10n 0w1n9t0 the effect5 0f 10n121n9rad1at10n c0up1ed w1th env1r0nment mu5t 6e under5t00d. 7h15 w0rk 5ummar12e5 the w1de-ran91n9 effect5 0f 10n121n9rad1at10n 0n the mechan1ca1 and 5tructura1 pr0pert1e5 0f med1ca1p01ymer5.

Keyw0rd5:Rad1at10n,Med1ca1p01ymer5,Mechan1ca1pr0pert1e5, Cr05511nk1n9,5c15510n,A91n9, 0x1dat10n

2.1 2.2 2.3 2.4 2.4.1 2.4.2 2.4.3 2.5

3.1 3.2 3.3 3.4 3.5

5ter1112at10n 0f 1mp1anta61e Dev1ce5 . . . . . . . . . . . . . . . . . .

64

6enera1 Effect5 0f 10n121n9 Rad1at10n 0n P01ymer5 . . . . . . . . .

66

1nteract10n 0f Rad1at10n w1th P01ymer5 . . . . . . . . . . . . . . . . . M01ecu1ar Chan9e5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . Free Rad1ca1 React10n5 . . . . . . . . . . . . . . . . . . . . . . . . . . 7he Effect 0f Env1r0nment . . . . . . . . . . . . . . . . . . . . . . . . A65ence 0f 0 x y 9 e n . . . . . . . . . . . . . . . . . . . . . . . . . . . .

66

Pre5ence 0f 0 x y 9 e n . . . . . . . . . . . . . . . . . . . . . . . . . . . . Effect5 0f 7emperature . . . . . . . . . . . . . . . . . . . . . . . . . . 7he Effect 0f 1rrad1at10n 0 n 5tructure and Mechan1ca1 Pr0pert1e5 . .

72 73 73

5pec1f1c Effect5 0f Rad1at10n 0n Med1ca1 P01ymer C1a55e5 . . . . . .

75

P01yethy1ene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . P01ypr0py1ene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . F1u0r0p01ymer5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . P01yacry1ate5 and P01ymethy1methacry1ate5 . . . . . . . . . . . . . . Ny10n5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

75 76 76 77 78

67 70 70 71

Advance5 1n P01ymer 5c1ence, V01. 162 • 5pr1n9er Ver1a9 8er11n He1de16er9 2003

64

L.A. Pru1tt

3.6 3.7 3.8

P01yurethane5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . P01ye5ter5 and 810de9rada61e P01ymer5 . . . . . . . . . . . . . . . . . Hydr09e15 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

78 79 79

4

Ca5e 5tud1e51n 0 r t h 0 p e d 1 c 5 . . . . . . . . . . . . . . . . . . . . . . .

80

4.1

4.3

Deter10rat10n 0f 0rth0ped1c 6rade UHMWPE Due t0 10n121n9 Rad1at10n . . . . . . . . . . . . . . . . . . . . . . . . . . . U5e 0f 10n121n9 Rad1at10n and L0w-7emperature P1a5ma Meth0d5 f0r C0ntr011ed Cr05511nk1n9 0f UHMWPE . . . . . . . . . . . . . . . 7he Effect5 0f 10n121n9 Rad1at10n 0n Acry11c 8a5ed 80ne C e m e n t 5 . .

5

5ummary .................................

4.2

Reference5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

80 85 89 91 91

L15t0f A66rev1at10n5 DNA E5R Et0 F71R FDA LDPE HDPE PE7 P6A PLA PMMA P7FE PVDF PVF UHMWPE

De0xyr160nuc1e1c ac1d E1ectr0n 5p1n Re50nance Ethy1ene 0x1de F0ur1er tran5f0rm 1nfrared Federa1 Dru9 Adm1n15trat10n L0w den51ty p01yethy1ene H19h den51ty p01yethy1ene P01y(ethy1ene terephtha1ate) P01y(91yc011c) ac1d (P6A) P01y(1act1c ac1d) P01ymethy1methacry1ate P01ytetraf1u0r0ethy1ene P01y(v1ny11dene f1u0r1de) P01y(v1ny1 f1u0r1de) U1tra h19h m01ecu1ar we19ht p01yethy1ene

1 5ter1112at10n0f 1mp1anta61e Dev1ce5 5ter1112at10n 0f 1mp1anta61e dev1ce5 15 a cr1t1ca1 c0ncern t0 the med1ca1 1ndu5try. 5uch dev1ce5 are e1ther 1mp1anted f0r 5h0rt durat10n 1n the 60dy 0r they are 1mp1anted w1th the 1ntent that they w111 ach1eve the1r funct10n f0r 5evera1 decade5, and 1n 50me ca5e5 f0r the durat10n 0fthe pat1ent•511fe. 7h15 re4u1re5 that the dev1ce

7he Effect5 0f Rad1at10n0n the 5tructura1 and Mechan1ca1Pr0pert1e5 0f Med1ca1P01ymer5

65

mu5t 6e 5ter11e at the t1me 0f 1mp1antat10n t0 m1n1m12e r15k 0f 1nfect10n and that the 5ter1112at10n meth0d ch05en mu5t n0t de9rade the pr0pert1e5 0f the 610med1ca1 mater1a1. 1nfect10n 15 an 1mp0rtant c0ncern f0r the med1ca1 dev1ce 1ndu5try. Wh11e the exact cau5e5 0f 1nfect10n rema1n unc1ear there appear5 t0 6e an a550c1at10n 0f 1mp1anted 610med1ca1 dev1ce5 w1th an enhanced 11ke11h00d f0r 1nfect10n [1, 2]. 7he pathway f0r 5uch 1nfect10n5 15 c0mp11cated and depend5 0n numer0u5 fact0r5 1nc1ud1n9 the mater1a1 u5ed 1n the dev1ce, a5 we11 a5 the dev1ce 10cat10n and expected 1mp1antat10n t1me [3]. F0r examp1e a catheter a550c1ated w1th 6a1100n an910p1a5ty may 6e 1n p1ace f0r m1nute5 wh11e a t0ta1 j01nt rep1acement dev1ce may 6e expected t0 funct10n 1n-v1v0 f0r tw0 decade5 0r m0re. 50me mater1a15 appear t0 6e m0re 5en51t1ve t0 6acter1a1 c0ntam1nat10n 6ecau5e 0f the1r c0mp051t10n, m1cr05tructure, de9ree 0f p0r051ty, 0r 5urface chem15try 0f the mater1a1 1t5e1f [4, 5]. Matthew5 et a1. [ 1] def1ne 5ter1112at10n a5 the rem0va1 0r de5truct10n 0f a11 m1cr00r9an15m5 fr0m a c0ntam1nated mater1a1 0r dev1ce. H0wever, the death 0f the m1cr00r9an15m 15 an exp0nent1a1 funct10n 0f 5tre55, and theref0re 1t 15typ1ca11y def1ned 6y 1t5 capa6111ty t0 meet an end-p01nt 5pec1f1cat10n. 1n the med1ca1 dev1ce 1ndu5try, the pr06a6111ty that the m1cr00r9an15m 0r 6acter1a1 c0ntam1nat10n w111 5urv1ve a 5ter1112at10n pr0cedure def1ne5 1t5 5ter111ty. 7he FDA a110w5 a dev1ce t0 6e 1a6e1ed a5 5ter11e 1f the num6er 0f n0n-5ter11e dev1ce5 15 1e55 than 0ne 1n a m11110n (1e55 than 0ne dev1ce 0ut 0f a 10t 0f 0ne m11110n can 5h0w 6101091ca1 c0ntam1nat10n). 5ter1112at10n meth0d0109y mu5t pr0v1de pathway5 f0r 5p0re death 0r mu5t render the m1cr00r9an15m 1ncapa61e 0f repr0duct10n 50 that the dev1ce cann0t 5upp0rt 6acter1a111fe 1n v1v0. 7he 51mp1e5t 5ter1112at10n techn14ue5 ut1112e e1evated temperature. 5team 15u5ed f0r penetra61e mater1a15 wh11e dry heat 15 u5ed f0r mater1a15 that are 1mpenetra61e t0 5team. 5aturated 5team 5ter1112at10n ut1112e5 temperature5 1n the ran9e 120135 °C f0r extended per10d5 0ft1me. Dry heat 5ter1112at10n u5e5 temperature51n the ran9e 160-180 °C. 7h15 p05e5 a un14ue pr061em t0 p01ymer1c 610mater1a15, wh1ch are 5en51t1ve t0 the e1evated temperature5.5ter1112at10n can a150 6e acc0mp115hed w1th chem1ca1 meth0d5 at 10wer temperature5. L0w temperature 5team can 6e c0up1ed w1th f0rma1dehyde and 5ter1112at10n can a150 6e acc0mp115hed 6y exp05ure t0 114u1d 91utara1dehyde. A 11m1tat10n 0f the5e meth0d5 15 that they can 1eave p05t5ter1112at10n chem1ca1 re51due5 0n the p01ymer1c dev1ce5. A chem1ca1 meth0d, wh1ch ha5 6een 4u1te 5ucce55fu11n the med1ca11ndu5try, 15 ethy1ene 0x1de (Et0) 9a5 (C2H20) 5ter1112at10n. 7h15 meth0d u5e5 an a1ky1at10n pr0ce55 t0 react w1th am1n0 ac1d5 and pr0te1n 9r0up5 f0r 610c1da1 act10n. 1n the 19705 Et0 wa5 the m05t pr0m151n9 10w temperature 5ter1112at10n techn0109y ava11a61e. 1t wa5 c0mm0n1y u5ed 1n med1ca1 dev1ce5 and wa5 ad0pted 6y numer0u5 0rth0ped1c5 and card10va5cu1ar c0mpan1e5 a5 the 5ter1112at10n meth0d 0f ch01ce. Et0 5ter1112at10n d0e5 have 11m1tat10n5 h0wever. 1t 15 a kn0w carc1n09en and mu5t 6e hand1ed w1th 9reat care. Furtherm0re, dev1ce5 5ter1112ed w1th th15 9a5 mu5t 6e 0ut-9a55ed f0r 5evera1 day5 1n 0r-

66

L.A. Pru1tt

der t0 rem0ve 9a5e0u5 c0ntam1nant5. F0r many med1ca1 c0mpan1e5, the5e 11m1tat10n5 were 5uff1c1ent t0100k f0r a1ternat1ve 5ter1112at10nmeth0d5 f0r the1r p01ymer1c dev1ce5.5evera1 med1ca11ndu5tr1e5 have n0w 100ked at 10w temperature 9a5 p1a5ma treatment a5 a v1a61e 5ter1112at10ntechn14ue [6]. 1n1t1a11y,h0wever, the maj0r1ty 0f the med1ca1 c0mmun1ty and 1n part1cu1ar the 0rth0ped1c5 1ndu5try 5w1tched t0 10n121n9 rad1at10n f0r 1t5 5ter1112at10n eff1c1ency and c05t effect1vene55. 10n121n9 rad1at10n 15 a meth0d capa61e 0f de11ver1n9 h19h effect1vene55 at re1at1ve1y 10w c05t. 7he5e treatment5 1nc1ude 9amma rad1at10n, X-ray5, 0r acce1erated e1ectr0n5. C06a1t 60 15 u5ed a5 the pr1mary 50urce f0r 9amma rad1at10n. 51nce 1t5 1ncept10n a5 a 5ter1112at10nt001 1n the 19605, 9amma rad1at10n 5ter1112at10n 15 perf0rmed at a 5tandard d05e 0f 2.5 Mrad (25 k6y). L1near acce1erat0r5 pr0v1de e1ectr0n 6eam5 at ener9y 1eve15that d0 n0t exceed 10 MeV 6ut are 11m1ted 1n depth 0f penetrat10n. 7he 610c1da1 eff1c1ency 0f 10n121n9 rad1at10n re11e50n free rad1ca1 f0rmat10n and 1t5 a6111tyt0 d1m1n15h DNA rep11cat10n 1n any 6acter1a1 5p0re 0r m1cr00r9an15m pre5ent 1n the med1ca1 dev1ce. A 6enef1t 0f 10n121n9 rad1at10n 15 that 1t 15 carr1ed 0ut at am61ent temperature, 1t can 6e thr0u9h penetrat1n9, and 1t re4u1re5 n0 0ut9a551n9 pr10r t0 1mp1antat10n. 10n121n9 rad1at10n 156e1n9 u5ed at an 1ncrea51n9 rate 6y the med1ca11ndu5try f0r the 5ter1112at10n 0f dev1ce5 c0mpr151n9 p01ymer c0mp0nent5 [7-9]. 7h15 ha5 cau5ed c0ncern 1n the 5c1ent1f1c c0mmun1ty a5 p01ymer5 typ1ca11yunder90 50me f0rm 0f rad1at10n-1nduced de9radat10n. 7h15 can ran9e fr0m m1n0r d15c010rat10n t0 5evere 0x1dat1ve em6r1tt1ement and deter10rat10n 0f 5tructura1 pr0pert1e5 [1012]. Under5tand1n9 the react10n5 0f rad1at10n chem15try w1th var10u5 p01ymer c1a55e5u5ed 1n 610med1ca1 dev1ce515 key t0 eva1uat1n9 the 10n9ev1ty 0f dev1ce5 5ter1112ed6y 10n121n9 meth0d5.

2 6enera1 Effect5 0f 10n121n9 Rad1at10n 0n P01ymer5 2.1 1nteract10n0f Rad1at10nw1th P01ymer5 1n 9enera1, the exp05ure 0fp01ymer5 t0 10n121n9rad1at10n w111a1ter the1r 6a51c m01ecu1ar 5tructure and a550c1ated macr05c0p1c pr0pert1e5.7he5e m01ecu1ar chan9e5 are 6r0u9ht a60ut thr0u9h a c0mp1ex 5et 0f react10n5 up0n exp05ure t0 rad1at10n ener9y. P01ymer5 are a1tered pr1mar11y thr0u9h 5evera1 6a51c 5cheme5: e1ectr0n a650rpt10n and 5u65e4uent c1eava9e that 91ve r15e t0 rad1ca1 f0rmat10n, rad1ca1 c0m61nat10n re5u1t1n9 1n the f0rmat10n 0f cr05511nk5, 0r d15pr0p0rt10nat10n t0 91ve 5c15510n, and 9a5 ev01ut10n [13-17]. 7he dep051t10n 0f h19h ener9y ph0t0n5, 5uch a5 9amma ray5, 1n a p01ymer 0ccur5 v1a three phy51ca1mechan15m5 [ 18]: C0mpt0n 5catter1n9 1n wh1ch an e1ectr0n 15 ejected wh11e the ph0t0n 155cattered, the ph0t0e1ectr1c effect where6y a ph0t0n 15 a650r6ed and an 0r61ta1 e1ectr0n 15 ejected, and

7he Effect50f Rad1at10n0n the $tructura1and Mechan1ca1Pr0pert1e50f Med1ca1P01ymer5

67

pa1r pr0duct10n 1n wh1ch a p051tr0n-e1ectr0n pa1r 15pr0duced. 1n 9enera1, C0mpt0n 5catter1n9 15the d0m1nant act1vated 1n p01ymer5. 7here are 5evera150urce5 0f 10n121n9 rad1at10n. 7he5e 1nc1ude 9amma ray5 9enerated fr0m a C06a1t-60 (1.17-1.33 MeV) 0r Ce51um-137 50urce (0.66 MeV), and e-6eam5 9enerated fr0m e1ectr0n acce1erat0r5 (0.1-10 MeV) 0r 8rem5trah1un9 Xray5 fr0m acce1erat0r5 (3-10 MeV) [ 19-23 ]. 7he 5tandard un1t 0f a650r6ed d05e 15 the 6ray (6y) wh1ch 15 e4u1va1ent t0 the ener9y 1mparted 6y 10n121n9 rad1at10n t0 a ma55 0f matter c0rre5p0nd1n9 t0 0ne j0u1e per k1109ram. 0 n e 6ray 15a150 e4u1va1ent t0 6.25x 108 eV/k9. An0ther c0mm0n un1t 0f rad1at10n d05e, 0ften enc0untered 1n the med1ca1 1ndu5try, 15 the rad, wh1ch 15 e4u1va1ent t0 the ener9y 0f a650rpt10n 0f 0.01 j0u1e per k1109ram (0.01 6y). 2.2 M01ecu1ar Chan9e5

M01ecu1ar chan9e5 6r0u9ht a60ut thr0u9h 10n121n9 rad1at10n are c0mm0n1y character12ed w1th a 6 fact0r that 4uant1f1e5 the y1e1d 0fan event [24, 25]. 7he5e event5 may 1nc1ude chan9e5 t0 m01ecu1ar we19ht, 9e1 c0ntent, 0r 0ther m01ecu1ar a1terat10n5.7he 6 fact0r 15 def1ned a5 the event y1e1d per 100 eV 0f ener9y and carr1e5 un1t5 0f 6tm01/J. M05t c0mm0n1y, the 6 fact0r5 are de5cr16ed f0r cr05511nk1n9 6(X), 5c15510n 6(5), and 9a5 ev01ut10n 6(9). M01ecu1ar we19ht 0f a p01ymer, and 1t5 d15tr16ut10n, can 6e dra5t1ca11ya1tered 6y exp05ure t0 10n121n9 rad1at10n. 7he5e h19h-ener9y treatment5 re5u1t 1n free rad1ca1 9enerat10n, ma1n cha1n 5c15510n and cr05511nk1n9, and 5u65e4uent1y a1ter the d15tr16ut10n 0f cha1n 512e 1n the 6u1k p01ymer. Much w0rk ha5 6een d0ne t0 deve10p the the0ret1ca16a515 f0r m01ecu1ar we19ht chan9e5 0w1n9 t0 h19h-ener9y rad1at10n exp05ure [26-29]. F0r a 11near p01ymer endur1n9 cha1n 5c15510n,the 6a51c f0rm 0f the e4uat10n de5cr161n9 the chan9e 1n m01ecu1ar we19ht d15tr16ut10n 15 91ven a5 [29] a,/,(p,y)

~y

•

p ~(p ,y) + 2p ~ ~(1~y) d1

where t

y =J rdt 0

r 15 the pr06a6111ty that a p01ymer cha1n under90e5 5c15510n 1n un1t t1me, p 15 the de9ree 0f p01ymer12at10n, and ~(p,y) 15 the we19ht fract10n 0f p01ymer m01ecu1e5 hav1n9p 5tructura1 un1t5.7he term 0n the 1eft de5cr16e5 the decrea5e 1n m01ecu1e5 hav1n9 p 5tructura1 un1t5 due t0 ma1n cha1n 5c15510n. 7he term 0n the r19ht de-

68

L.A. Pru1tt

5cr16e5 the 1ncrea5e 0f the m01ecu1e5 hav1n9 p 5tructura1 un1t5 due t0 5c15510n5 0f th05e m01ecu1e5 hav1n9 1 un1t5.7he 501ut10n t0 the a60ve e4uat10n take5 the f0rm [29]

where 0(p,0) 15the 1n1t1a1we19ht fract10n. 7he 6 fact0r f0r 5c15510n, 6(5) take5 the f0rm [29]: 6(5) = 100 NA y Rd Where Rd 15 the rad1at10n d05e and N A 15Ava9adr0•5 num6er. 7he num6er avera9e de9ree 0f p01ymer12at10n, P., 1n the a65ence 0f any cr05511nk1n9 15 91ven a5 [29]: pn 1 =un 1 + y where u~ 15 the num6er avera9e de9ree 0f p01ymer12at10n pr10r t0 1rrad1at10n. 1f M~, 1and M~ are the num6er avera9e m01ecu1ar we19ht pr10r t0 and 5u65e4uent t0 1rrad1at10n, re5pect1ve1y,then: Uy -

(Mn, 1 - M n) Mn

7h15 1nd1Cate5 that the a1terat10n5 t0 the num6er avera9e m01eCU1ar We19ht depend 0n1y 0n M~, 1 and the 5c15510n5 per 5tructura1 un1t rather than 0n the 1n1t1a1 m01ecu1ar we19ht d15tr16ut10n. H0wever, chan9e5 t0 the we19ht avera9e m01ecu1ar we19ht re5u1t1n9 fr0m rad1at10n-1nduced 5c15510n d0 depend 0n the 1n1t1a1m01ecu1ar we19ht d15tr16ut10n. F0r the ca5e 0fan 1n1t1a1un1f0rm d15tr16ut10n, the re1at1ve chan9e 1n we19ht avera9e m01ecu1ar we19ht take5 the f0rm [29]: M w • 2(un - 1 + e 7un ) Mw,1

(uny) 2

F0r the ca5e 0f an 1n1t1a1rand0m d15tr16ut10n, the re1at1ve chan9e 15 91ven a5: Mw

1

Mw,1

(1+ unY)

When 0n1y de9radat10n 0ccur5 w1th1n the p01ymer, the ev01ut10n 0f m01ecu1ar we19ht d15tr16ut10n w111appr0ach that 0f a rand0m ca5e, 5uch that M, JM~=2.

7he Effect5 0f Rad1at10n0n the 5tructura1 and Mechan1ca1Pr0pert1e5 0f Med1ca1P01ymer5

69

Under c0nd1t10n5 0f 51mu1tane0u5 cr05511nk1n9 and 5c15510n,the 6 fact0r take5 the f0rm:

6 ( X ) = 100 NA x Rd Where x 15 the num6er 0f cr05511nk5 per 5tructura1 un1t, 0r cr05511nk den51ty. 1f 5c15510n and cr05511nk1n9 0ccur at the 5ame t1me 1t 15 typ1ca11ya55umed that they are 1ndependent event5.7hat 15, the ev01ut10n 1n m01ecu1ar we19ht can 6e determ1ned 6y 5umm1n9 the effect 0f 5c15510n and then 5u65e4uent1y the effect cr05511nk1n9. F0r 5uch ca5e5, the num6er avera9e m01ecu1ar we19ht chan9e5 15 de5cr16ed a5 [29]:

Mn

1

Mn, 1 - 1+ u n ( y - x) A5 6ef0re, the num6er avera9e m01ecu1ar we19ht 15 n0t a funct10n 0f the 1n1t1a1 m01ecu1ar we19ht d15tr16ut10n. 7he we19ht avera9e m01ecu1ar we19ht, h0wever, d0e5 depend 0n the 1n1t1a1d15tr16ut10n. F0r an 1n1t1a1rand0m d15tr16ut10n, the re1at1ve chan9e 1n we19ht avera9e m01ecu1ar we19ht 15 91ven a5:

Mw

1

Mw,1

1+un(y-4x)

and f0r a un1f0rm 1n1t1a1d15tr16ut10n:

Mw

2(e uny + uny• 1)

Mw,1

1uny2-4unx(e unY+uny-1)]

F0r the ca5e 0f cr05511nk1n9 w1th0ut 5c15510n effect5, the p01ymer w1111ncrea5e the m01ecu1ar we19ht unt11 1t5 va1ue 6ec0me5 1nf1n1te1y1ar9e. A5 th15 0ccur5, 9e1at10n 0ccur5 1n the p0rt10n 0fthe p01ymer that 15 1n501u61e 1n any 501vent, 1ncrea5e5 w1th rad1at10n d05e. 7he p01nt at wh1ch the very 5ame 9e1 15 f0rmed 15termed the 9e1 p01nt and the c0nc0m1tant cr05511nk den51ty at th15 p01nt, x9, 15 def1ned a5 [29]: 1

x9 - 2Pw,1 7he num6er 0f cr05511nk5 at the 9e1 p01nt 15 e4ua1 t0 ha1f the rat10 0f the t0ta1 num6er 0f 5tructura1 un1t5 t0 the we19ht avera9e de9ree 0f p01ymer12at10n pr10r t0 cr05511nk1n9, Pw,#

70

L.A. Pru1tt

2.3 Free Rad1ca1React10n5 F0r p01ymer1c mater1a15 the pr1mary mechan15m 0f dama9e 0ccur5 v1a free rad1ca1 f0rmat10n. Park1n50n [18] ha5 0ut11ned the 6a51c 5tep5 f0r the 9enerat10n 0f react1ve free rad1ca15 re5u1t1n9 fr0m 10n121n9 treatment. 7he dama9e 15 1n1t1ated w1th the eject10n 0f a h19h-ener9y e1ectr0n. 7he react10n 15 dep1cted 6e10w: R ~ R + + e-} 9enerat10n 0f free e1ectr0n e - +R--+R + + 2e-} 10n12at10n R + + e - --+R*} h19h1y exc1ted e1ectr0n 5tate5 7he5e h19h1y exc1ted e1ectr0n 5tate5 may under90 rad1at10n1e55 0r rad10act1ve decay. 7hey may a150 decay thr0u9h a chem1ca1 pathway v1a heter01yt1c 60nd c1eava9e 1ead1n9 t0 the 9enerat10n 0f 10n5 0r v1a h0m01yt1c 60nd c1eava9e re5u1t1n9 1n the 9enerat10n 0f free rad1ca15: RX* --+ R ° + X ° } free rad1ca1 f0rmat10n 1n 9enera1, f0r p01ymer5, 1t 15 the free rad1ca1 9enerat10n that d0m1nate5.7h15 1ead5 t0 free rad1ca1 react10n5 that depend 0n the chem15try 0f the p01ymer and may 6e c0up1ed w1th the env1r0nment. 5uch react10n5 can re5u1t 1n ma1n cha1n 5c15510n, rec0m61nat10n, 0r d15pr0p0rt10nat10n a5 examp1ed 6e10w 1n p01yethy1ene: - ( 0 H 2 - 0H2) - ---->- (H02 ° + •0H2)- } ma1n cha1n 5c15510n -(• 0 H 2 + •0H2)- ---->- ( 0 H 2 - 0 H 2 ) - } rec0m61nat10n - ( 0 H 2 -• 0 H 2 +• 0 H 2 ) - ---->- ( 0 H = 0 H 2 + 0 H 3 ) - } d15pr0p0rt10nat10n 1f the 51de 9r0up 0f the p01ymer 15 1nv01ved 1n 5c15510n, 5ma11 rad1ca1 fra9ment5 are 9enerated, 5uch a5 a hydr09en rad1ca1.7he dan9er 1n th15 react10n 15 that th15 5ma11 rad1ca1 15 h19h1y react1ve and m0611e, and 1t may 6e a61e t0 d1ffu5e 9reat d15tance5 tr199er1n9 numer0u5 react10n5. 2.4 7he Effect 0f Env1r0nment 10n121n9 treatment can re5u1t 1n cha1n 5c15510n 0r cr05511nk1n9 depend1n9 0n the env1r0nment 1n wh1ch the rad1at10n 15 perf0rmed, and the ava11a6111ty0f react1ve 9a5e5 0r rad1ca15 w1th1n the p01ymer 1t5e1f. Further, 5u5cept16111ty t0 0ne de9rada-

7he Effect5 0f Rad1at10n0n the 5tructura1 and Mechan1ca1Pr0pert1e5 0f Med1ca1P01ymer5

71

t10n 5cheme 0r the 0ther 15d1ctated 6y the 1ntr1n51c6ack60ne chem15try 0f the p01ymer. Many p01ymer5 under90 60th 5c15510n and cr05511nk1n9, 6ut 0ften 0ne mechan15m pred0m1nate5. 2.4.1

A65ence0f 0xy9en 7he nature 0f the p01ymer 5tructure determ1ne5 1t5 re5p0n5e and phy51ca1 chan9e up0n exp05ure t0 10n121n9 rad1at10n. 1n 9enera1, a5 5h0wn 6e10w, the p01ymer5 0f 7ype (A) w111under90 a pred0m1nant 5c15510nmechan15m wh11e p01ymer5 0f 7ype (8) w1116e 5u5cept161e t0 cr05511nk1n9: - 7ype A: (CH2-CR• R••) fav0r5 5c15510n - 7ype 8: (CH2-CHR) fav0r5 cr05511nk1n9 A5 an examp1e, p01y(methy1methacry1ate) (PMMA) 15 repre5entat1ve 0f a 7ype A p01ymer w1th 51de 9r0up5, R•=CH 3 and R••=C00CH 3 and 1t pred0m1nate1y de9rade5 v1a cha1n 5c15510n.0 n the 0ther hand, p01y(methy1 acry1ate) 15a 7ype 8 p01ymer w1th 51de 9r0up R = C 0 0 C H 3 and 1t read11y cr05511nk5.1n 9enera1, p01ymer5 w1th h19h c0ncentrat10n5 0f 4uaternary car60n at0m5 a10n9 the cha1n under90 5c15510nwh11ep01ymer51ack1n9 th15 feature pred0m1nant1y cr05511nk.7he pre5ence 0f un5aturat10n 1n the p01ymer cha1n a1d5 th15 effect and enhance5 the y1e1d 0f cr05511nk1n9 (natura1 ru66er 15 an examp1e). A150, the pre5ence 0f ar0mat1c 9r0up5 10wer the y1e1d 0f any react10n due t0 rad1at10n (p01y5tyrene 150ne 0f the m05t rad1at10n re515tant p01ymer5). 7a61e 1 pr0v1de5 a 5ummary 0f the 9enera1 p01ymer 5cheme5 that are 5u5cept161e t0 e1ther cr05511nk1n9 0r 5c15510n.

1a61e1.5ummary0fthe 9enera1p01ymer 5d1erne5wh1ch are 5u5cept161et0 e1thercr05511nk1n9 0r 5c15510nwhen 5u6ject t0 10n121n9rad1at10n 1n the a65ence 0f 0xy9en P01ymer5 pr0ne t0 5c15510n

P01ymer5 pr0ne t0 cr05511nk1n9

P01y(methy1methacry1ate) P01y1506uty1ene P01y0¢-methy15tyrene P01y(v1ny11denech10r1de) P01y(v1ny1f1u0r1de) P01yacry10n1tr11e P01ytetraf1u0rethy1ene Ce11u105eand der1vat1ve5 DNA

P01yethy1ene P01ypr0py1ene P01y5tyrene P01yacry1ate5 P01yam1de5 P01y(v1ny1ch10r1de) P01ye5ter5 Un5aturated e1a5t0mer5 Natura1 ru66er

72

L.A. Pru1tt

2.4.2

Pre5ence0f 0xy9en 7he am61ent env1r0nment dra5t1ca11y affect5 the re5p0n5e 0f a p01ymer t0 rad1at10n exp05ure. When 10n121n9 rad1at10n 15 perf0rmed 1n a1r there can 6e a 5evere pr0pen51ty f0r 5tructura1 de9radat10n 0f the p01ymer. M05t p01ymer5, even th05e that cr05511nk 1n an 1nert env1r0nment, w111have a tendency t0 under90 cha1n 5c15510n when 0xy9en 15 ava11a61e dur1n9 10n12at10n [30, 31 ]. 1n 5uch ca5e5, the 9enera1 c1a551f1cat10n de5cr16ed 1n 7a61e 1 15 n0 10n9er va11d. A150 dama9e 0ften 0ccur5 at much 10wer rad1at10n d05e5, and de9radat10n 6ec0me5 a t1me dependent pr0ce55. 7he t1me dependent mechan15m 0f free rad1ca1 react10n5 p05e5 5er10u5 c0ncern f0r rad1at10n de9radat10n 0f p01ymer5, part1cu1ar1y 1n the pre5ence 0f 0xy9en due t0 1t5 h19h d1ffu510na1 m06111ty and react1v1ty. Park1n50n [18] ha5 0ut11ned the free rad1ca1 react10n5 1n rad1at10n-1nduced p01ymer 0x1dat10n a5 f0110w5: R - y-+R ° } 1n1t1at10n R ° - 02--->R02 ° } pr0pa9at10n R02 ° - RH--+R02H + R °} R 0 2 H - RH--+R0 ° + •0H}

cha1n 6ranch1n9

R0• - RH--+R0H + R•} • 0 H - RH--+H20 + R R02H, R02 °, R ° --+ 5c15510n and cr05511nk1n9 2R02•--+R02 R + 0 2 } term1nat10n 7he h19h d1ffu510na1 m06111ty 0f 0xy9en pr0v1de5 a 9reater penetrat10n 1nt0 p01ymer and re5u1t5 1n the 9enerat10n 0f react1ve free rad1ca15 that can 6e 10n9-11ved. 0xy9en trap5 free rad1ca15 and dr1ve5 react10n5 that are 0x1dat1ve 1n nature. 7he5e chem1ca1 react10n5 re5u1t 1n the 9enerat10n 0f 0x1dat1ve pr0duct5 created w1th1n the p01ymer and 1nc1ude the f0rmat10n 0f car60xy11c ac1d5, ket0ne5, e5ter5, a1c0h01 der1vat1ve5, and per0x1de 6a5ed 5pec1e5 [32, 33]. Free-rad1ca1 react10n5 re5u1t 1n 9a5e0u5 pr0duct5, and 1n the pre5ence 0f 0xy9en the5e can 1nc1ude car60n d10x1de, car60n m0n0x1de, and water vap0r. When per0x1de5 de9rade, cha1n 6ranch1n9 15 fav0red and react10n5 re5u1t 1n further rad1ca1 9enerat10n. 7h15 pr0v1de5 a pathway f0r the 9enerat10n 0f numer0u5 free rad1ca15 w1th1n the p01ymer. Add1t10na11y, the per0x1de dec0mp051t10n 15 temperature dependent. 7h15 re5u1t5 1n a p01ymer that ha5 60th a t1me and temperature dependent de9radat10n mechan15m. M0re0ver,

7he Effect50f Rad1at10n0n the 5tructura1 and Mechan1ca1Pr0pert1e50f Med1ca1P01ymer5

73

the depth 0f 0x1dat10n w1th1n the p01ymer depend5 0n the 0xy9en-permeat10n rate5 and c0n5umpt10n rate5 per a650r6ed d05e a5 we11a5 the d05e rate 1t5e1f.7hu5 the p01ymer ha5 far 1e555ta6111tythan 1t5 c0unter part rad1ated 1n an 1nert env1r0nment. 5uch p05t-1rrad1at10n de9radat10n 5cheme5 can render a p01ymer 60th 0x1d12ed and em6r1tt1ed [34]. 7h15 ha5 5er10u5 c0n5e4uence5 f0r the med1ca1 dev1ce 1ndu5try that u5e5 9amma rad1at10n f0r 5ter1112at10n and re11e5 0n 5ta6111ty0f 5he1f 5t0ra9e pr10r t0 1mp1antat10n. 1n 5uch 1n5tance5 the deta115 0fthe 5ter1112at10n env1r0nment and 5u65e4uent 5he1f5t0ra9e 6ec0me param0unt t0 10n9-term 1nte9r1ty 0fthe p01ymer. 2.4.3

Effect5 0f 7emperature 7he temperature dur1n9 1rrad1at10n can have a pr0f0und effect 0n the rad1at10n chem15try. 8e10w the 91a55 tran51t10n temperature, a 1ar9e num6er 0f 5ta61e rad1ca15 are 9enerated and trapped 1n the 91a55y 5tate [35]. C0rre5p0nd1n91y, th15 reduce5 the net cr05511nk1n9 due t0 1mm06111ty 1n the 91a55y5tate. A60ve the 91a55 tran51t10n temperature, the tendency t0ward cr05511nk1n9 0r 5c15510n 15 enhanced depend1n9 0n the p01ymer chem15try. F0r examp1e, 1n p01yethy1ene 1f 1rrad1at10n 15 d0ne at 114u1d n1tr09en temperature5 a11y1d0u61e 60nd5 are prevented fr0m f0rm1n9.0n the 0ther hand, 1f p01yethy1ene 15 1rrad1ated 1n the me1t the y1e1d 0f cr05511nk5 15 9reat1y enhanced. P01y5tyrene 5h1ft5 1t5 tendency fr0m cr05511nk1n9 t0 5c15510n a5 the temperature 15 6r0u9ht a60ve the 91a55 tran51t10n temperature. 1n 50me f1u0r0p01ymer5, the 0pp051te trend 15 065erved. Cr05511nk1n9 15 fav0red at temperature5 a60ve the 91a55 tran51t10n. 7he effect 0f temperature can 6e further acce1erated 1n the pre5ence 0f mechan1ca15tre55e5 0n the mater1a1 [36]. 7h151511ke1ythe re5u1t 0fweakened chem1ca1 60nd5 under 5tre55 and the p1a5t1c121n9 effect 0f the p01ymer v1a rad10chem1ca1 pr0duct5. 2.5 7he Effect 0f 1rrad1at10n 0n 5tructure and Mechan1ca1 Pr0pert1e5

Dur1n91rrad1at10n, 5em1cry5ta111nep01ymer5 under90 5tructura1 chan9e5 re5u1t1n9 1n 1mperfect10n5 1n the cry5ta111nepha5e. 1n 9enera1, a5 h19her de9ree5 0f rad1at10n are 5u5ta1ned the cry5ta111ne5tructure ev01ve5 t0 a de9raded 5tructure re5u1t1n9 1n an acc0mpany1n9 decrea5e 1n the cry5ta111ne me1t1n9 p01nt, 7m. P01y(ethy1ene terephtha1ate) exh161t5 a 25 K depre5510n 1n me1t1n9 p01nt when rad1ated t0 a d05e 0f 2000 Mrad [37]. 1n 50me 1n5tance5, the p01ymer w1111ncrea5e 1t5 net cry5ta111n1ty and den51ty w1th 1ncrea51n9 rad1at10n. An examp1e 0f th15 15 u1tra h19h m01ecu1ar we19ht p01yethy1ene (UHMWPE). 8ecau5e UHMWPE ha5 a very h19h m01ecu1ar we19ht (-4-6 m11110n9/m01) and a re1at1ve1y10w cry5ta111n1ty(-50%), the re5u1t 0f

74

L.A. Pru1tt

10n121n9 rad1at10n 15 a 5c15510n-6a5ed pr0ce55 re5u1t1n9 1n 5ma11er cha1n5. 7he 5ma11er cha1n5 pack m0re eff1c1ent1yand re5u1t 1n an 1ncrea5ed den51ty and cry5ta111n1tyup0n 1rrad1at10n [38]. 51m11ar effect5 are 065erved 1n P7FE and p01y(v1ny11dene f1u0r1de) PVDE 7he effect 0f 1ncrea51n9 cry5ta111n1tyand den51ty can a1ter 6a51c mechan1ca1 pr0pert1e5 5uch a5 y1e1d 5tre55 and m0du1u5. 1n 9enera1, f0r f1ex161ep01ymer5 that exper1ence cr05511nk1n9 a5 a re5u1t 0f 10n12at10n, the e1a5t1c m0du1u5 tend5 t0 1ncrea5e wh11e the 5tra1n t0 fa11ure decrea5e5. W1th 1ncrea51n9 d05e, the p01ymer 6ec0me5 5t1ffer, harder and at a 5uff1c1ent1yh19h d05e 1t 6ec0me5 6r1tt1e. F19ure 1 5h0w5 the effect 0f rad1at10n d05e 0n a p01ych10r0prene p01ymer. F0r f1ex161e p01ymer5 5u5cept161e t0 5c15510n, the mechan1ca1 pr0pert1e5 5uch a5 ten511e 5tren9th, m0du1u5, and e10n9at10n decrea5e w1th d05e. F0r the5e p01ymer5 the mechan1ca1 pr0pert1e5 are c0nt1nu0u51y d1m1n15hed and may u1t1mate1y ev01ve 1nt0 v15c0u5 114u1d5. F1ex161ep01ymer5 and e1a5t0mer5 are c0mm0n1y 5u5cept161e t0 rad1at10n-1nduced dama9e wh11e 91a55y p01ymer5 and cr05511nked re51n5 tend t0 6e m0re re5111ent. 61a55y p01ymer5 that under90

10a

6--

~

6--

~,~

4

-

10

8 6

1

105

5

106

5

1Q 7

A650t6ed d05e~6y

F19,1,7he effect 0f rad1at10nd05e 011the mechan1ca1pr0pert1e5 0f a p0]ych]0r0prene p0]ymer,

E den0te5 e10n9at10n at 6reak, H repre5ent5 5h0re D hardne55, and R repre5ent5 the ten511e 5tren9th [18]

7he Effect50f Rad1at10n0n the 5tructura1and Mechan1ca1Pr0pert1e50f Med1ca1P01ymer5

75

cr05511nk1n9 are re515tant t0 deter10rat10n and exper1ence 11tt1echan9e 1n the1r mechan1ca1 pr0pert1e5. M0du1u5 15 0ften reta1ned 1n 91a55yp01ymer5 that are 5u5cept161e t0 5c15510n6ut ten511e 5tren9th 15105tw1th 1ncrea51n9 rad1at10n d05e. H0wever, at 10w cr05511nk1n9 1eve15 6r0u9ht a60ut thr0u9h 1rrad1at10n, p01y5tyrene can 6e a1tered fr0m a 91a55yp01ymer t0 a ru66ery mater1a1 a5 the p01ymer 6ehave511ke an e1a5t1c netw0rk a60ve 1t5 91a55 tran51t10n temperature [39]. Cr05511nked, therm05ett1n9 p1a5t1c5 are h19h1y re515tant t0 rad1at10n dama9e 6ecau5e 0f the1r h19h c0ncentrat10n 0f p01ar 9r0up5 and 1nterm01ecu1ar d1p01e-d1p01e 1nteract10n5. 3 5pec1f1c Effect5 0f Rad1at10n 0n Med1ca1 P01ymer C1a55e5 3.1 P01yethy1ene

P01yethy1ene ha5 numer0u5 app11cat10n5 1n the med1ca1 1ndu5try ran91n9 fr0m catheter5 t0 6ear1n9 5urface5 f0r j01nt rep1acement5 [40, 41]. A5 0ne 0f the m05t v1a61e c0mmerc1a1 p01ymer5, p01yethy1ene ha5 6een the 5u6ject 0f exten51ve rad1at10n 5tud1e5.1n fact, there 15 a p1eth0ra 0f re5earch dev0ted t0 the cr05511nk1n9 0f p01yethy1ene f0r c0mmerc1a1 app11cat10n5 ran91n9 fr0m paraff1n5 t0 UHMWPE [38, 42-47]. A5 prev10u51y de5cr16ed, when p01yethy1ene 15 exp05ed t0 an 10n121n9 rad1at10n env1r0nment 1n the a65ence 0f 0xy9en 1t w111 fav0r cr05511nk1n9. 7he cr05511nk5 9enerated are 10cated pr1mar11y 1n the n0n-cry5ta111ne pha5e and a10n9 the 1ame11ar-am0rph0u5 1nterpha5e [42]. When p01yethy1ene 15 1rrad1ated 1n the me1t a 9reater den51ty 0f cr05511nk5 can 6e created at the expen5e 0f the cry5ta111ne pha5e. 1n 9enera1 w1th 1ncrea51n9 cr05511nk den51ty there 15 a c0nc0m1tant reduct10n 1n cry5ta111n1ty.Further, a5 a re5u1t 0f the 6ack60ne 5tructure 0f the p01yethy1ene cha1n, there w1116e 5evera1 un14ue re5p0n5e5 t0 10n121n9 rad1at10n 1nc1ud1n9 the 9enerat10n 0f hydr09en 9a5, the un5aturat10n 0f tran5v1ny1ene 60nd5, the de9radat10n 0f v1ny1 end 9r0up5, and capa6111tyf0r h19h cr05511nk eff1c1ency.7ran5 v1ny1ene un5aturat10n d0e5 n0t depend 0n the m01ecu1ar we19ht 6ut 15 11near1ydependent 0n the rad1at10n d05e mak1n9 1t a 5ucce55fu1d051meter [48]. 1n 9enera1, 10n121n9 rad1at10n v1a e-6eam 0r 9amma ray5 that re5u1t5 1n cr05511nk1n9 15 c0n51dered 6enef1c1a1 t0 the mechan1ca1 pr0pert1e5 0f p01yethy1ene. M0derate cr05511nk1n9 1n HDPE re5u1t5 1n an 1ncrea5e 1n 60th y1e1d 5tren9th and ten511e m0du1u5 [38]. F0r UHMWPE, rad1at10n 1n the me1t re5u1t5 1n a h19h y1e1d 0f cr05511nk1n9 w1th 11tt1e5c15510n.W1th 1ncrea51n9 cr05511nk den51ty there 15 a c0rre5p0nd1n9 ev01ut10n 0f cry5ta111te m0rph0109y fr0m 1ame11ar t0 m1ce11ar [49]. Cr05511nk1n9 0f UHMWPE 15 0f 9reat 1ntere5t t0 the 0rth0ped1c5 c0mmun1ty. Recent 5tud1e5 0n the wear 6ehav10r 0f h19h1y cr05511nked UHMWPE u5ed a5 the 6ear1n9 5urface f0r t0ta1 j01nt rep1acement5 5u99e5t5 that cr05511nk1n9 c0u1d dra5t1ca11y1mpr0ve the wear re515tance 0f UHMWPE [50-54].

76

L.A. Pru1tt

0 n the 0ther hand, 1f precaut10n5 are n0t taken t0 prevent the pre5ence 0f m01ecu1ar 0xy9en at the t1me 0f 1rrad1at10n, p01yethy1ene w111under90 a d0m1nant 5c15510n mechan15m. 7h15 ha51ead t0 numer0u5 em6r1tt1ement pr061em5 a550c1ated w1th 0x1dat10n and cha1n 5c15510n [9-12]. 7h15 rad1at10n chem15try p1a9ued the 0rth0ped1c5 c0mmun1ty f0r year5 when many med1ca1 dev1ce c0mpan1e5 ut1112ed 9amma rad1at10n 1n a1r a5 the pr1mary 5ter1112at10n meth0d [55]. A ca5e 5tudy de5cr161n9 the effect5 0f 10n121n9 rad1at10n 0n UHMWPE and the 1mp11cat10n5 f0r the med1ca1 c0mmun1ty 15pr0v1ded 6e10w.

3.2 P01ypr0py1ene P01ypr0py1ene, 1n 1t5 150tact1c 5em1cry5ta111nef0rm, 15 c0mm0n1y u5ed 1n n0n-re50r6a61e 5uture5. 7h15 therm0p1a5t1c p01ymer under90e5 60th cr05511nk1n9 and 5c15510n mechan15m5 when 1rrad1ated. 7h15 p01ymer 5uffer5 fr0m p05t-rad1at10n deter10rat10n 0f mechan1ca1 pr0pert1e5 re9ard1e55 0f whether 0xy9en 15 pre5ent 0r a65ent at the t1me 0f rad1at10n [56]. H0wever, 0x1dat1ve de9radat10n d0m1nate5 th15 p05t rad1at10n ev01ut10n 1n phy51ca1 pr0pert1e5 and re5u1t5 1n a reduct10n 0f m0du1u5, ten511e5tren9th, and 5tra1n t0 fa11ure [57]. 7he 1055 0f5tra1n t0 fa11ure f0110w5 f1r5t 0rder k1net1c5 and re5u1t5 1n a reduct10n fr0m 900% e10n9at10n t0 fa11ure t0 va1ue5 appr0ach1n9 20% at a rad1at10n d05e 0f 160 Mrad [58, 59].

3.3 F1u0r0p01ymer5 F1u0r0p01ymer5 are fu11y0r part1a11yf1u0r1nated p01y01ef1n5that pr0v1de chem1ca1 1nertne55, therma1 re515tance, mechan1ca1 dura6111ty, and 1u6r1c1ty. 7he5e un14ue pr0pert1e5 are due t0 the f1u0r1ne 5heath that pr0tect5 the car60n 6ack60ne fr0m chem1ca1 attack. M05t f1u0r0car60n p01ymer5 are 5em1cry5ta111nedue t0 the 5pat1a1 pack1n9 eff1c1ency 0f the 11near 0r he11ca1p01ymer cha1n5. F1u0r0p01ymer5 are u5ed 1n a w1de var1ety 0f med1ca1 app11cat10n5 ran91n9 fr0m va5cu1ar 9raft5 t0 m1cr0f1u1d1c dev1ce5 [60]. Wh11e there are a w1de ran9e 0f f1u0r0p01ymer5 ava11a61e,the u5e 0f the5e mater1a15 f0r 610med1ca1 app11cat10n5 15 pred0m1nant1y 6a5ed 0n p01ytetraf1u0r0ethy1ene 1n expanded f0rm. 7he 5ucce55 0f th15 610mater1a1 ha5 re5u1ted fr0m 1t5 m1cr0 p0r0u5 5tructure, wh1ch a110w5 610-1nte9rat10n f0r f1xat10n and pr0v1de5 5tructura1 1nte9r1ty. 7he m05t 5ucce55fu1 med1ca1 app11cat10n5 0f e-P7FE are f0und 1n card10va5cu1ar 5ur9ery where e-P7FE va5cu1ar 9raft5 are u5ed f0r ve55e1 rec0n5truct10n. 1n 0rth0ped1c 5ur9ery, e-P7FE ha5 6een u5ed a5 a rep1acement f0r the anter10r cruc1ate 119ament5 1n the knee. A5 w1th a11med1ca1 dev1ce51t 1511ke1y that th15 p01ymer can 6e 5u6jected t0 10n121n9 rad1at10n a5 a 5tandard 5ter1112at10n 5cheme.

7he Effect50f Rad1at10n0n the 5tructura1 and Mechan1ca1Pr0pert1e50f Med1ca1P01ymer5

77

F1u0r0p01ymer5, 91ven the1r chem1ca1 and 5tructura1 1nertne55, are 5urpr151n91y 5u5cept161e t0 p05t-rad1at10n de9radat10n [61 ]. M0re0ver, the re5u1t1n9 re5p0n5e t0 10n121n9 rad1at10n depend5 0n the 6ack60ne chem15try 0f the f1u0r0p01ymer. A5 a 9enera1 ru1e, there 15 a 9reater 11ke11h00d f0r cr05511nk1n9w1th 1ncrea5ed hydr09en 0n the p01ymer 6ack60ne. 50 PVF w111fav0r cr05511nk1n9 wh11e P7FE w1116e 5u5cept161e t0 de9radat10n. 7he 1atter 15very 5u5cept161e t0 5c15510npr0ce55e5, and 1n fact 10n121n9 rad1at10n can 6e u5ed t0 ta110r the m01ecu1ar we19ht 0f th15 p01ymer c0mmerc1a11y [62]. 51m11ar t0 p01yethy1ene, P7FE 15 p1a9ued w1th per0xy-6a5ed free rad1ca1 9enerat10n when exp05ed t0 10n121n9 rad1at10n, and 5uch rad1ca15 are 10n9-11ved 1n the p01ymer. Hedv19 [63] ha5 1nve5t19ated the ten511e pr0pert1e5 0f 9amma rad1ated P7FE and ha5 f0und a 90% reduct10n 1n 5tra1n t0 fa11ure and near1y a 40% reduct10n 1n ten511e 5tren9th. L1ke p01yethy1ene, the cry5ta111n1ty0f P7FE 15 f0und t0 1ncrea5e w1th 1ncrea51n9 rad1at10n d05e up t0 100 Mrad due t0 5c15510n mechan15m5.8ey0nd th15 d05e p01nt the cry5ta111n1ty15reduced due t0 an 1ncrea5e 1n free v01ume 0f the p01ymer [63]. Deter10rat10n 0f 5tructura1 pr0pert1e5 0f P7FE can 6e m1n1m12ed 1f rad1at10n 15perf0rmed 1n a vacuum env1r0nment. 1n th15 ca5e cr05511nk1n9 mechan15m5 can 6e act1vated and 1ncrea5e5 1n ten511e 5tren9th can 6e ach1eved. 3.4 P01yacry1ate5 and P01ymethy1methacry1ate5

P01yacry1ate5 and p01ymethy1methacry1ate5 are c0mm0n1y u5ed a5 med1ca1 adhe51ve5, and can 6e f0und c0mm0n1y 1n the f0rm 0f60ne cement5 and denta1 re51n5 [40]. Wh11e the5e p01ymer5 appear t0 6e 4u1te 51m11ar 1n the1r 6ack60ne chem15try, a5 ment10ned a60ve, there are 5u6t1e d1fference5 that render very d1fferent react10n5 t0 10n121n9 rad1at10n. P01y(a1ky1 acry1ate5) under90 cr05511nk1n9 when exp05ed t0 rad1at10n, wh11e p01y (a1ky1 methacry1ate5) de9rade very rap1d1y thr0u9h 5c15510n 5cheme5.1n fact the 1atter de9rade5 50 eff1c1ent1ythat th15 p01ymer 15u5ed a5 a p051t1ve e1ectr0n 6eam re515t [64]. 51m11ar1yp01yacry1ate5 are 4u1te 5ta61e when rad1ated 6y 10n121n9 meth0d5; h0wever p01ymethy1methacry1ate 15 5u5cept161e t0 5c15510n and 15 5u5cept161e t0 5evere 1055 1n 5tren9th a5 a c0n5e4uence [18]. 7h15 de9radat10n and the acc0mpany1n91055 0f mechan1ca1 pr0pert1e5 are 111u5trated 1n F19.2. D1cken50n [65] ha5 5h0wn that the num6er 0f ma1n cha1n 5c15510n515 pr0p0rt10na1 t0 rad1at10n d05e 1n PMMA. A ca5e 5tudy de5cr161n9 the effect5 0f 10n121n9 5ter1112at10n 0n the 5tructure and mechan1ca1 pr0pert1e5 0f acry11c 6a5ed 60ne cement5 15pr0v1ded 6e10w.

78

L.A. Pru1tt 80

1~

[

1

[

60

9• 40

20

1

1

f

7

0.01

0.02

0.03

0.04

0.05

5tra1n, c m / c m

F19.2.5tre55-5tra1n6ehav10rf0r PMMA exp05ed t0 f0ur d05e5 0f 9anm1a rad1at10n 1n an 1nert env1r0nment at 25 °C: (A) 40 Mrad, (8) 20 Mrad, (C) 4 Mrad, (D) un1rrad1ated [18]

3.5 Ny10n5 Ny10n5 are c0mm0n1y u5ed a5 a 5uture mater1a1 1n the med1ca1 1ndu5try and 1n 50me 1n5tance5 they are u5ed 1n p01ymer1c 6a1100n5 f0r 6a1100n an910p1a5ty [40]. 0 n the wh01e, ny10n 15 character12ed a5 a cr05511nka61e p01ymer 6ut th15 c1a55 0f p01y1m1de515 5u5cept161e t0 60th 5c15510nand cr05511nk1n9.7h15 6ehav10r ha5 6een 11nked t0 the num6er 0f methy1ene 9r0up5 0r hydr09en at0m5 0n the p01ymer 6ack60ne [66]. 7he5e p01ymer5, 11ke p01yethy1ene, are dra5t1ca11y affected 6y the env1r0nment 1n wh1ch 1rrad1at10n 15 perf0rmed. 1n the a65ence 0f 0xy9en there 15 11tt1e chan9e 1n ten511e 5tren9th w1th 1ncrea51n9 d05e; h0wever, 1n the pre5ence 0f a1r there 15 5u65tant1a1 dr0p 1n 60th 5tren9th and e10n9at10n t0 6reak. Ny10n5 can 6e 5ta61112edw1th the add1t10n 0f an ar0mat1c 9r0up - the a11phat1c p01y1m1de5 are 4u1te re5111entt0 rad1at10n dama9e.

3.6 P01yurethane5 7herm0p1a5t1c p01yurethane5 have 6r0ad app11ca6111ty1n the med1ca1 p1a5t1c5 1ndu5try and m05t n0ta61y 1n catheter5 [67]. 7herm0p1a5t1c p01yurethane5 are 610ck c0p01ymer5 that c0mpr15e am0rph0u5 and cry5ta111ne610ck5.7he f0rmer d1ctate5 the e1a5t1c1tywh11e the 1atter determ1ne5 the 5t1ffne55and 5tren9th. 7he am0rph0u5 610ck5 are 0ften c0mp05ed 0f ether5 0r e5ter5.7he ether5 are ut1112ed where 10w temperature f1ex16111ty,m1cr061a1 re515tance, and hydr01yt1c 5ta6111ty are needed,

7he Effect50f Rad1at10n0n the 5tructura1 and Mechan1ca1Pr0pert1e50f Med1ca1P01ymer5

79

wh11e e5ter5 are u5ed where tear 5tren9th, a6ra510n re515tance, and t0u9hne55 are re4u1red [67]. 1n 9enera1, cr05511nk1n9v1a rad1at10n 15 u5ed t0 1mpr0ve the 5tren9th, a6ra510n re515tance, and m0du1u5 0f the5e p01ymer5.7h15 ena61e5 the p01ymer t0 6e 1nject10n m01ded 1nt0 c0mp1ex 5hape5 and then cured v1a 10n121n9 rad1at10n. 3.7 P01ye5ter5 and 810de9rada61e P01ymer5

P01ye5ter5 are u5ed 1n numer0u5 610med1ca1 app11cat10n5. P01y(ethy1ene terephtha1ate) a150 kn0wn a5 PE7 15u5ed pred0m1nant1y 1n w0ven fa6r1c f0rm f0r card10va5cu1ar pr05the5e5. 7hey are u5ed f0r arter1a1 patche5 and 1ar9e d1ameter va5cu1ar pr05the5e5 [40]. A11phat1c p01ye5ter5 5uch a5 p01ycapr01act0ne are 610de9rada61e p01ymer5 w1th app11cat10n5 ran91n9 fr0m re50r6a61e 5uture5 t0 c0ntr011ed dru9 de11very dev1ce5. P01y(91yc011c)ac1d (P6A) and p01y(1act1c ac1d) (PLA) are the m05t w1de1y u5ed 610er0da61e p01ymer5. P6A 15 u5ed 1n re50r6a61e 5uture5 and 0ffer5 enhanced 5tren9th due t0 1t5 re1at1ve1yh19h cry5ta111n1ty.7he am0rph0u5 f0rm 0f PLA 15u5ed f0r dru9 de11very wh11e the 5em1cry5ta111nef0rm 15u5ed 1n de9rada61e 5uture5 0r f0r re50r6a61e 10ad 6ear1n9 dev1ce5 5uch a5 0rth0ped1c 5crew5. 7he mechan15m 0f 610de9radat10n 15 6r0ad1y cate90r12ed 1nt0 three mechan15m5: c1eava9e 0f cr05511nk56etween water 501u61e cha1n5, c1eava9e 0f 51de cha1n51ead1n9 t0 the f0rmat10n 0f p01ar 9r0up5, 0r ma1n cha1n c1eava9e. 8ecau5e 5c15510n 15 the pred0m1nant re5p0n5e 0f the5e p01ymer5 t0 rad1at10n, 9reat care mu5t 6e made when 5ter11121n9the5e p01ymer5.10n121n9 rad1at10n can a1ter the rate 0f de9radat10n and can 1ead t0 premature fa11ure 0f the5e dev1ce5. F0r th15 rea50n many re50r6a61e p01ymer5 are 5ter1112edw1th Et0 0r p1a5ma meth0d5. 3.8 Hydr09e15

Hydr09e15 are cr05511nked water-5w011en p01ymer1c 5tructure5 that are c0mm0n1y u5ed 1n dru9 de11very and t155ue en91neer1n9 app11cat10n5 [40]. Hydr09e15 are made 6y 5we111n9 cr05511nked p01ymer5 1n 6101091ca1 f1u1d5 0r water. 7he cr05511nked 5tructure 15 c0mm0n1y prepared w1th 10n121n9 meth0d5 5uch a5 9amma ray5, Xray5, e-6eam, 0r u1trav101et 119ht. 8ecau5e 10n121n9 meth0d5 are u5ed f0r the cr05511nk1n9 mechan15m, 5ter1112at10n 15typ1ca11yd0ne w1th n0n-10n121n9 meth0d5 5uch a5 Et0 0r p1a5ma 50 that the cr05511nk1n9 d05e and 5tructura1 1nte9r1ty 0f the hydr09e15 can 6e c0ntr011ed.

80

L.A. Pru1tt

4 Ca5e 5tud1e5 1n 0rth0ped1c5 7he u5e 0f p01ymer5 1n 0rth0ped1c5 re4u1re5 an 1mp1ant mater1a1 that t01erate5 1ar9e f1uctuat1n9 5tre55e5 due t0 c0ntact 10ad5, 0ffer5 exce11ent tr1601091ca1 perf0rmance, and pr0v1de510n9-term 5tructura15ta6111ty. F0r th15 rea50n the 0n1y 5ucce55fu1 p01ymer u5ed at the art1cu1at1n9 5urface 15u1tra h19h m01ecu1ar we19ht p01yethy1ene (UHMWPE). 8ecau5e 0f 1t5 except10na11y h19h m01ecu1ar we19ht and t1e m01ecu1e den51ty th15 p01ymer 0ffer5 except10na1 fat19ue, wear, and a6ra510n re515tance. Further, 1n 1t5 6u1k f0rm 1t 15 h19h1y 610c0mpat161e. 1t 15 5u5cept161e t0 dama9e, h0wever, under 10n9-term cyc11c10ad5 1n v1v0.7h15 ha5 6een f0und t0 6e exacer6ated 6y the effect5 0f 10n121n9 rad1at10n when u5ed a5 a 5ter1112at10n techn14ue. 51m11ar effect5 have 6een f0und 1n acry11c 6a5ed 60ne cement5, wh1ch are u5ed t0 1nte9rate the 0rth0ped1c dev1ce 1nt0 the 5urr0und1n9 60ne t155ue. 5tud1e5 addre551n9 the effect 0f 10n121n9 rad1at10n 1n 0rth0ped1c p01ymer5 have 9reat1y c0ntr16uted t0 the under5tand1n9 0f the 5tructura1 ev01ut10n re5u1t1n9 fr0m exp05ure t0 rad1at10n 50urce5 a550c1ated w1th 5ter1112at10n and pr0ce551n9.7he5e 5tud1e5 are rev1ewed 6e10w.

4.1 Deter10rat10n0f 0rth0ped1c6rade UHMWPEDue t0 10n121n9Rad1at10n 5ter1112at10n v1a 10n121n9 rad1at10n ha5 6een the pr1mary cu1pr1t 1n the 10n9-term de9radat10n 0f UHMWPE u5ed f0r t0ta1 j01nt rep1acement5. A5 recent1y a5 1995, UHMWPE wa5 cu5t0mar11y 5ter1112edw1th 9amma rad1at10n 1n the pre5ence 0f a1r u51n9 a n0m1na1 d05e 0f 25 k6y. 1n 1998, m05t Un1ted 5tate5 0rth0ped1c C0mpan1e5 had tran51t10ned the1r 5ter1112at10ntechn14ue5 t0 0ne 0f a few meth0d5 1nc1ud1n9 9amma rad1at10n 1n an 1nert env1r0nment 0r a n0n-10n121n9 5ter1112at10nmeth0d u51n9 ethy1ene 0x1de 0r 9a5 p1a5ma. 7h15 chan9e 1n 5ter1112at10npract1ce wa5 m0t1vated 6y the p1eth0ra 0f 5c1ent1f1c11terature 1nd1cat1n9 that 9amma 5ter1112at10n 1n a1r pr0m0ted 0x1dat1ve cha1n 5c15510nand 10n9-term de9radat10n 0f de51ra61e phy51ca1, chem1ca1, and mechan1ca1 pr0pert1e5 0f UHMWPE [55, 68-76]. Maj0r 0rth0ped1c c0mpan1e5 have d15c0nt1nued 5ter1112at10n 0f UHMWPE c0mp0nent5 u51n9 9amma rad1at10n 1n the pre5ence 0f a1r; h0wever, the 10n9-term deter10rat10n 0f th15 p01ymer rema1n5 a c11n1ca11yre1evant pr061em. 7he rea50n f0r th15 c0nt1nued cha11en9e 15 that an e5t1mated f0ur m11110nU.5. pat1ent5 have 6een 1mp1anted w1th an UHMWPE c0mp0nent that wa5 5ter1112ed 1n a1r dur1n9 the per10d 1980-1995, when 9amma 1rrad1at10n 1n a1r wa5 the re9u1ar 5ter1112at10n pract1ce. A5 d15cu55ed a60ve, free rad1ca15 9enerated 6y 10n121n9 rad1at10n w1th1n UHMWPE are vu1nera61e t0 0x1dat10n dur1n9 5he1f a91n9 and after 1mp1antat10n. Premnath et a1. [55] 5u99e5ted that 5he1f a91n9 1n a1r repre5ent5 a m0re extreme 0x1dat1ve cha11en9e f0r 1rrad1ated UHMWPE than 1n v1v0 0x1dat10n, 6ecau5e the

7he Effect5 0f Rad1at10n0n the 5tructura1 and Mechan1ca1Pr0pert1e5 0f Med1ca1P01ymer5

8]

c0ncentrat10n 0f d15501ved 0xy9en 1n a1r ha5 appr0x1mate1y an 0rder 0f ma9n1tude 9reater c0ncentrat10n 0f 0xy9en than that d15501ved1n the 5urr0und1n9 60dy f1u1d5 under phy5101091ca1 c0nd1t10n5. Rad1at10n 5ter1112at10n 0f UHMWPE 1n a1r, f0110wed 6y 10n9-term 5he1f a91n9,15 n0w under5t00d t0 re5u1t 1n de9radat1ve chan9e5 t0 the phy51ca1, chem1ca1, and mechan1ca1 pr0pert1e5 0f the p01ymer [77-79]. F0r th15 rea50n 5he1f a91n9 ha5 6ec0me the f0cu5 0f numer0u5 recent 5tud1e5 1n an attempt t0 under5tand and rep11cate the 0x1dat10n 0f UHMWPE. P05t-1rrad1at10n a91n9 ha5 6een 51mu1ated u51n9 a c0m61nat10n 0f therma1 c0nd1t10n1n9 and e1evated 0xy9en part1a1 pre55ure5. Acce1erated a91n9 pr0t0c015 have 6een emp10yed n0t 0n1y t0 d1fferent1ate the effect5 0f 9amma 5ter1112at10n 1n a1r, 6ut a150 t0 eva1uate the 0x1dat10n re515tance 0f UHMWPE 5ter1112ed6y a1ternat1ve meth0d5. 7here are tw0 current1y accepted te5t1n9 5trate91e5 that are c0n51dered a5 v1a61e acce1erated a91n9 pr0t0c015 f0r UHMWPE. 7he f1r5t meth0d deve10ped 6y 5un et a1. prec0nd1t10ned 5pec1men5 1n a 5tandard a1r furnace at 80 °C f0r up t0 23 day5, a16e1t at a c0ntr011ed, 510w 1n1t1a1heat1n9 rate 0f appr0x1mate1y 0.6 °C/m1n [80]. 7h15 5tudy ut1112ed a c0ntr01 9r0up 0fUHMWPE c0mp0nent5 that had 6een 9amma rad1at10n 5ter1112ed1n a1r pr10r t0 acce1erated 0x1dat10n 0r 5he1f a91n9 f0r up t0 10 year5.5un et a1. f0und that, after 23 day5 0f prec0nd1t10n1n9, the max1mum 0x1dat10n 1ndex 1n the 5pec1men5 c0rre5p0nded t0 that 0f 7-9 year5 0f5he1f a91n9. A1th0u9h 5un and c011ea9ue5 matched the peak 0x1dat10n 1ndex 6etween the prec0nd1t10ned and 5he1f a9ed c0mp0nent5, a 5u65e4uent 5tudy 5h0wed that the d15tr16ut10n 0f 0x1dat10n thr0u9h the th1ckne55 d1ffered 6etween the tw0 9r0up5 [81]. 7he 5he1f-a9ed c0mp0nent5 5h0wed a 5u65urface 0x1dat10n peak, wh11e the art1f1c1a11y a9ed c0mp0nent5 had a max1mum 0x1dat10n at the 5urface. 7he 5ec0nd meth0d dev15ed 6y 5anf0rd and 5aum 1n 1995 [82] emp10yed a rap1d techn14ue f0r acce1erat1n9 0x1dat1ve de9radat10n 1n UHMWPE. 5pec1men5 were a9ed 1n pure 0xy9en under f1veatm05phere5 0fpre55ure at 70 °C f0r up t0 5even day51n 0rder t0 ach1eve a 5u65urface 0x1dat10n peak, 51m11ar t0 that 065erved 1n retr1eved c0mp0nent5. C0mpar1n9 the 6u1k avera9e 0x1dat10n 1ndex fr0m prec0nd1t10ned c0mp0nent5 w1th that fr0m 5he1f-a9ed c0mp0nent5 va11dated the1r meth0d. 1t wa5 f0und that 0ne week 0fprec0nd1t10n1n9 at 70 °C and f1veatm05phere5 0f pure 0xy9en re5u1ted 1n 0x1dat10n e4u1va1ent t0 f1vet0 ten year5 0f am61ent 5he1f a91n9.1t 5h0u1d 6e n0ted that acce1erated 0x1dat10n meth0d5 f0r UHMWPE are n0t w1th0ut the1r 11m1tat10n5. F0r examp1e, 1n a m0rph0109y 5tudy 0f UHMWPE that wa5 9amma-rad1at10n 5ter1112ed1n a1r and then prec0nd1t10ned u51n9 5un•5 meth0d, Crane et a1. [83] f0und the cry5ta111ne m0rph0109y 1n the prec0nd1t10ned 5pec1men5 wa5 n0ta61y d1fferent than 1n 5he1f-a9ed c0mp0nent5. Further re5earch 15 needed 0n the mechan1ca1 6ehav10r and m0rph0109y 0f UHMWPE t0 e1uc1date the d1fference5 6etween therma1 c0nd1t10n1n9 and 10n9-term 5he1f a91n9. 7he 1eve1 0f 0x1dat10n 1n a9ed UHMWPE c0mp0nent5 that have a9ed 0n the 5he1f, 1n-v1v0, 0r thr0u9h acce1erated mean5 can 6e 4uant1f1ed u51n9 5pectr05c0p1c techn14ue5. Kurt2 et a1. perf0rmed numer0u5 va11dat10n 5tud1e5 t0 en5ure repr0duc-

82

L.A. Pru1tt

L75 [,50

"2

1.25

57ER1LE

8 1.00 0
rnuc1eu5. 1n add1t10n, acc0rd1n9 t0 F19. 12, LE7 decrea5e5 w1th 1ncrea51n9 5pec1f1c ener9y, 50 that even a d1rect h1t may n0t 6e 5uff1c1ent t0 k111a ce11.7heref0re 1nact1vat10n cr055-5ect10n5 decrea5e w1th 1ncrea51n9 ener9y 1n the ca5e 0f 119hter 10n5 11ke, e.9., car60n. F0r 1ntermed1ate heavy part1c1e5 60th 0f the effect5 de5cr16ed a60ve c0ntr16ute, 50 that decrea5e 0f LE7 m0re 0r 1e55 c0mpen5ate5 f0r the 1ncrea51n9 track d1ameter. U51n9 F19. 12, the 5y5temat1c5 de5cr16ed a60ve can 6e c0nverted t0 the 5y5temat1c5 0f 0 a5 a funct10n 0f LE7. 7he character15t1c h00k 5tructure thu5 15 a c0n5e4uence 0f the var1at10n 0f track d1ameter w1th part1c1e ener9y. 7he d0m1nance 0f the phy51ca1 a5pect5 0ftrack 5tructure at very h19h LE7 15 further 5upp0rted 6y the 51m11ar1ty 0f the 0(LE7)-dependenc1e5 f0r d1fferent 6101091ca1 5y5tem5 and endp01nt5 a5 5ummar12ed, e.9., 6y Kraft [78]. 1n 9enera1, they a11 exh161t a pr0n0unced h00k 5tructure f0r 10n5 heav1er than ar90n a5 dem0n5trated a150 1n F19. 22. 4.6 0xy9en Effect

F0r 10w-LE7 rad1at10n a pr0n0unced dependence 0f rad105en51t1v1ty 0n the 0xy9en 5upp1y 15 065erved. 7h15 effect 151ar9e1y reduced f0r h19h-LE7 rad1at10n, and near1y van15he5 f0r LE7>1000 keV/9m (5ee F19.24). 7h15 feature 0fh19h-LE7 rad1at10n 15 expected t0 6e a remarka61e advanta9e 1n tum0r therapy. 7he re515tance 0f hyp0x1c ce115, even 1f 0n1y c0ntr16ut1n9 a5 a very 5ma11 fract10n t0 the t0ta1 tum0r ma55, can 11m1t the pr06a6111ty 0f tum0r cure 1n the ca5e 0f c0nvent10na1 rad1at10n. 1n c0ntra5t, f0r h19h-LE7 rad1at10n, acc0rd1n9 t0 the re5u1t5 de5cr16ed a60ve, hyp0x1c

132

M. 5ch012 1

1

,

1

1

111

1

1

1

1

,

,

,1,

1

,

3.5

1

1

1

1

1,1

1

2X He, 8arend5en et aL

3.0 ~

0

•

0

C, 81ake1yet a1.

[]

Ar, 81ake1yet aL

2.5

AA

D Lx ~ ~A []

2.0

1.5

[] AA

1.0 1

10°

2

1

J

5

1

1

1111

1

101

2

1

~

J

5

J

J1J1

102 LE7 [keV 1 11m]

J

2

1

1

~

5

~

~J~1

~

103

J

1

2

F19.24. Dependence 0f 0xy9en enhancement rat10 0n LE7 f0r d1fferentpart1c1e5. (Data redrawn fr0m [79, 80])

ce115exh161t a 51m11ar5en51t1v1tya5 n0rm0x1c ce115and 5h0u1d thu5 a110w a 519n1f1cant 1ncrea5e 0f tum0r c0ntr01 1n the ca5e 0f tum0r5 w1th hyp0x1c ce11fract10n5.

4.7 7he R01e 0f 1ncrea5ed 10n12at10nDen51ty 7he exp1anat10n 0f the 5y5temat1c5 0f R8E and 0 a5 a funct10n 0f part1c1e ener9y and LE7 were 1ar9e1y6a5ed 0n ar9ument5 c0ncern1n910n12at10n den51ty. 1ncrea5ed 10n12at10n den51ty wa5 a55umed t0 1ead t0 m0re c0mp1ex and thu5 1e55 repara61e dama9e. A1th0u9h p1au5161e, the5e ar9ument5 need 0f c0ur5e further c0nf1rmat10n fr0m exper1menta1 data. 7h15 5ect10n 5ummar12e5 exper1ment5 5h0w1n9 m0re d1rect1y the 1nf1uence 0f the 1ncrea5ed 10n12at10n den51ty 0f char9ed part1c1e rad1at10n 0n the c0mp1ex1ty and repara6111ty 0f dama9e.

4.7.1 D0u61e 5trand 8reak 1nduct10nand Rej01n1n9 1ntu1t1ve1y 0ne w0u1d expect the 1ncrea5ed 10n12at10n den51ty t0 1ead t0 a h19her y1e1d 0f5evere dama9e, e.9., D58.5urpr151n91y 5uch a h19her rate 0fD58 pr0duct10n ha5 n0t 6een f0und; R8E va1ue5 f0r D58 1nduct10n are very c105e t0 0ne even 1n LE7-re910n5 where the R8E f0r 5urv1va1 15 519n1f1cant1yenhanced [81 ]. 06v10u51y,

Effect5 0f 10n Rad1at10n 0n Ce115and 7155ue5

133

there 15n0 51mp1e c0rre1at10n 6etween D58 1nduct10n and 1etha11ty.H0wever, 1t ha5 t0 6e kept 1n m1nd that the mea5urement5 0f D58 1nduct10n 6a5ed 0n 9e1 e1ectr0ph0ret1c meth0d5 91ve avera9e y1e1d5,6ut n0 c0nc1u510n5 can 6e drawn 0n the 5pat1a1 d15tr16ut10n 0f D585 w1th1n the 1nd1v1dua1ce115.F0r examp1e, when c0n51der1n9 a 91ven num6er 0f D585, the1r 6101091ca1effect m19ht we11depend 0n whether they are a11pr0duced a5 c1u5ter51n a 5ma115u6v01ume 0fthe nuc1eu5 (a5 w0u1d 6e expected f0r part1c1e track5) 0r h0m09ene0u51y d15tr16uted thr0u9h0ut the nuc1eu5. C1u5ter5 0f D58 c0n5t1tute a m0re c0mp1ex type 0f dama9e wh1ch 15m0re d1ff1cu1tt0 repa1r. 7h15 15c0n515tent w1th re5u1t5 fr0m 5tud1e5 0f the rej01n1n9 0f DNA fra9ment5. 7he5e 5tud1e5 1nd1cate that, a1th0u9h the 1n1t1a1y1e1d 0f D58 15 51m11ar f0r d1fferent rad1at10n type5, the re51dua1 dama9e after h19h-LE7 rad1at10n 15 u5ua11y h19her due t0 the reduced repara6111ty 0f the c0mp1ex dama9e 1nduced. Re51dua1 dama9e 15 thu5 th0u9ht t0 6e the m0re appr0pr1ate mea5ure 0f 1etha11ty than the pr1mary 1nduced dama9e. F19ure 25 91ve5typ1ca1 examp1e5 0fthe rej01n1n9 k1net1c5 after X-1rrad1at10n and 1rrad1at10n w1th 10w ener9et1c N1 10n5.80th the t1me c0n5tant a5 we11 a5 the fract10n 0f re51dua1 dama9e are 519n1f1cant1y1ncrea5ed f0r the 10w ener9y n1cke11rrad1at10n. 7h15 f1nd1n9 15 fu11y c0mpat161e w1th the chan91n9 510pe 0f the 5urv1va1

1

1

1

1

1

1

N110 MeV/u

0~5 C3

0.2

0.1 X-ray5 0.05

0

1

2

3 4 1ncu6at10n t1me (h)

5

6

F19.25.1nf1uence 0f rad1at10n 4ua11ty 0n the rej01n1n9 0f d0u61e 5trand 6reak5 1n C H 0 ce115. 7 h e re1at1ve fract10n5 0 f D 5 8 are n0rma112ed t0 the 1n1t1a1n u m 6 e r 0 f D 5 8 065erved at t 0 . 7 h e d05e va1ue5 f0r ph0t0n and n1cke1 10n 1rrad1at10n were adju5ted t0 1nduce appr0x1mate1y the 5ame a6501ute n u m 6 e r 0f D58 at t 0. (C0urte5y 6.7aucher-5ch012)

134

M. 5ch012

curve5, the van15h1n9 5h0u1der at 10w ener9y 6e1n9 an 1nd1cat0r 0f the m0re c0mp1ex and thu5 1e55repara61e dama9e. A1th0u9h the 5tandard a55ay f0r detect10n 0f rej01n1n9 d0e5 n0t 1ead t0 c0nc1u510n5 a60ut the f1de11ty0f the rej01n1n9 pr0ce55, m0re deta11ed 1nve5t19at10n5 revea1ed that c105e v1c1n1ty 0f DNA dama9e actua11y 1ead5 t0 a 519n1f1cant1yh19her rate 0f m15repa1r pr0ce55e5 [82 ]. H0wever, 1t 15 n0t 0n1y the 5pat1a1 v1c1n1ty0f D58 wh1ch m19ht 1nf1uence the effect1vene55.1n part1cu1ar c0m61nat10n5 0f d1fferent type5 0f dama9e, e.9., D58 p1u5 6a5e dama9e 0r even c1u5ter5 0f dama9e c0nta1n1n9 n0 D58, wh1ch are pr0duced much m0re fre4uent1y, are d15cu55ed a5 re1evant c0mp1ex dama9e [22]. 4.7.2 Chr0m050meA6errat10n5

1nve5t19at10n 0f chr0m050me a6errat10n5 a150 revea1ed the 1nf1uence 0f rad1at10n 4ua11ty 0n the rate 0f rej01n1n9 and repa1r 0f D58. F0r examp1e, the y1e1d 0f exchan9e type a6errat10n5, re4u1r1n9 rej01n1n9 0f chr0m050me fra9ment5 1nduced 6y at 1ea5t tw0 D58 1n tw0 chr0m050me5, 15 519n1f1cant1y5ma11er f0r h19h-LE7 rad1at10n than f0r 10w-LE7 rad1at10n. C0mp1ementar11y, the rate 0f chr0mat1d 6reak5 15 c0n51dera61y enhanced [31 ]. 1n c0ntra5t, after c0nvent10na1 X-1rrad1at10n, the dama9e 15d15tr16uted h0m09en0u51y thr0u9h0ut the nuc1eu5, 50 that the 1nv01vement 0f many chr0m050me5 15 much m0re 11ke1y,1ead1n9 a150 t0 the h19her rate 0f exchan9e type a6errat10n5 6etween d1fferent chr0m050me5. A part1cu1ar1y 1mpre551ve c0n5e4uence 0f the extreme1y 10ca112ed ener9y dep051t10n 155h0wn 1n F19.26.1t 5h0w5 a m1t0t1c ce111rrad1ated w1th 10w ener9et1c, very heavy 10n5. Wherea5 m05t chr0m050me5 appear unaffected 6y 1rrad1at10n, 1n 0ne 51n91e chr0m050me a hu9e num6er 0f 6reak5 15 1nduced, 1ead1n9 t0 a part1cu1ar type 0f a6errat10n ca11ed •d151nte9rat10n• [83]. Due t0 the 5pat1a1 5eparat10n 0f 1nd1v1dua1 chr0m050me terr1t0r1e5 dur1n9 m1t0515, 1t 15 very 11ke1ythat a 51n91e part1c1e traver5a1 thr0u9h the nuc1eu5 0n1y dama9e5 a 51n91e 0r few chr0m050me5, 1eav1n9 the rema1n1n9 chr0m050me5 t0ta11y unaffected. 51m11ar pattern5 0f chr0m050me dama9e have 6een a150 f0und after 1rrad1at10n 0f ce115w1th extreme1y f0cu5ed 1a5er-UV-1rrad1at10n [84]. 4.7.3 Fract10nated1rrad1at10n

Further ev1dence f0r the 5ever1ty and c0mp1ex1ty 0f h19h-LE7 1nduced dama9e c0me5 fr0m 5tud1e5 0f fract10nated 1rrad1at10n. Here, the t0ta1 1rrad1at10n d05e 15 91ven 1n tw0 0r m0re fract10n5 w1th a certa1n t1me 1nterva11n 6etween. Dur1n9 th15 t1me 1nterva1, ce115are 1ncu6ated under 0pt1ma1 c0nd1t10n5, 50 that at 1ea5t part 0f

Effect5 0f 10n Rad1at10n0n Ce115and 7155ue5

~

~

~

~

~

135

~

...........................1.1..1.1.1.1.111111111.1.1.11

F19.26. 065ervat10n 0f chr0m050ma1 d151nte9rat10n (arr0w) after 1rrad1at10n 0f m1t0t1c ce115 w1th 10wener9et1c,veryheavy part1c1e5.7hec0mp1etede5truct10n0fpart5 0fthe chr0m050me can 6e exp1a1ned6y the extremdy h19h 10n12at10nden51tyw1th1nthe part1de track (C0urte5y 5. R1tter)

the dama9e can 6e repa1red, 1ead1n9 t0 an 0vera11 decrea5ed effect 0f fract10nated c0mpared t0 51n91e d05e exp05ure. F0r ph0t0n 1rrad1at10n the5e effect5 are 9enera11y very pr0n0unced. 1n c0ntra5t, w1th 1ncrea51n9 LE7 the fract10nat10n effect decrea5e5 and eventua11y c0mp1ete1y d15appear5; 1n 50me ca5e5 even an enhanced effect1vene55 15 rep0rted [85]. 7h15 1nd1cate5, that n0 repa1r 0f radat10n dama9e 15p055161e 1n the 1nterfract10nat10n 1nterva1, 5upp0rt1n9 the v1ew 0f m0re c0mp1ex dama9e 1nduced 6y part1c1e rad1at10n. 4.7.4

D1rect V15ua112at10n0f L0ca112edDama9e M0re recent1y, new meth0d5 have 6een app11ed t0 v15ua112e d1rect1y the 10ca112ed dama9e 1nduced 6y part1c1e rad1at10n. 7he5e meth0d5 are 6a5ed 0n 1mmun0f1u0re5cent 5ta1n1n9 0f nuc1ear 51te5 c0nta1n1n9 pr0te1n51nv01ved 1n DNA repa1r. Accumu1at10n 0f the5e pr0te1n5 15 th0u9ht t0 6e an 1nd1cat0r 0f part1cu1ar 5evere and pr06a61y 1rrepara61e dama9e [86, 87]. F19ure 27 5h0w5 an examp1e 0f 5uch an exper1ment, dem0n5trat1n9 accumu1at10n 0fthe p21-pr0te1n c0nf1ned t0 the 51te5 0f part1c1e traver5a15.7he 6eam d1rec-

136

M. 5ch012

Cell nucleus

\

)

F19.27a-c. V15ua112at10n 0f the 10ca112ed DNA dama9e 6y 1mmun0f1u0re5cent meth0d5: a pha5e c0ntra5t m1cr05c0p1c1ma9e 0fhuman f16r061a5tce115;6 1mmun05ta1n1n90fp21-pr0te1n after 1rrad1at10n 0fthe ce115w1th 10.1 MeV/u Ca 10n5.7he 1ma9e 15taken at exact1y the 5ame p051t10n a5 the pha5e c0ntra5t 1ma9e a the p051t10n and 5hape 0f a ce11nuc1eu5 15 1nd1cated f0r c0mpar150n; c p051t10n 0fthe 1nd1v1dua1part1c1etrack5 a5 065erved 1n nuc1ear track detect0r5 0n wh1ch the ce115were 9r0wn. A5 1nd1cated6y the 0ut11ne 0fthe ce11nudeu5, the 1mmun05ta1n1n9pattern 5h0wn 1n 6 ref1ect5 the track pattern 1n c and thu5 c0nf1rm5, that the 6101091ca1re5p0n5e 15c0nf1ned t0 the 5ma11re910n5 0f h19h 10n12at10nden51tyw1th1n the track

Effect5 0f 10n Rad1at10n0n Ce115and 7155ue5

137

t10n 15perpend1cu1ar t0 the 1ma9e p1ane 1n F19.27, and each 5p0t 1n the ce11nuc1eu5 h19h119hted 1n the m1dd1e pane11nd1cate5 the traver5a10f a 51n91e10n. 7h15 ha5 6een pr0ven 6y c0rre1at10n 0f the f1u0re5cent 5p0t5 w1th the 1ma9e 0f etched 10n track5 a5 5h0wn 1n the 10wer pane1, taken fr0m exact1y the 5ame p051t10n 0f the 5amp1e [88 ]. A1th0u9h the part1cu1ar r01e 0f the p21-pr0te1n 1n th15 re5p0n5e t0 part1c1e 1nduced dama9e 15 n0t yet kn0wn, 1t5 c010ca112at10n w1th 0ther pr0te1n5 1nv01ved 1n DNA repa1r 5u99e5t5 a new r01e 1n DNA dama9e pr0ce551n9.7he 10ca112ed accumu1at10n 0f the5e pr0te1n5 15c0mp1ete1y c0mpat161e w1th the d15tr16ut10n 0f dama9e expected acc0rd1n9 t0 the 10ca1 d05e d15tr16ut10n5 a5 5h0wn 1n F19. 11. 4.8 8y5tander Effect5

7he term•6y5tander effect• 15u5ed t0 de5cr16e 51tuat10n5 where n0t 0n1y the pr1mar11ydama9ed ce115re5p0nd t0 rad1at10n, 6ut a150 ne19h60r1n9 ce1155h0w a re5p0n5e w1th0ut 6e1n9 d1rect1y dama9ed. 7h1515 part1cu1ar1y re1evant 1n the ca5e 0f char9ed part1c1e rad1at10n 6ecau5e 0f the1r 5t0cha5t1c pr0pert1e5. D11ut1n9 the avera9e d05e c0rre5p0nd5 t0 a decrea5e 0f the part1c1e f1uence and thu5 the avera9e num6er 0f traver5a15 n. 7heref0re, 1n the ca5e 0f n