POLYMERS AS BIOMATERIALS POLYMERS AS BIOMATERIALS Edited by Shalaby W. Shalaby ETHICON, Inc. A Johnson & Johnson Company Somerville, New Jersey Allan S. Hoffman Buddy D. Ratner and Thomas A. Horbett University of Washington Seattle, Washington PLENUM PRESS • NEW YORK AND LONDON Library of Congress Cataloging in Publication Data Main entry under title: Polymers as biomaterials. "Proceedings of a symposium on polymers as biomaterials, held March 22 - 25, 1983, at the American Chemical Society meeting in Seattle, Washington"-T.p. verso. Bibliography: p. Includes index. 1. Polymers in medicine-Congresses. 2. Polymers in medicine-Physiological ef fect-Congresses. 3. Colloids in medicine-Congresses. 4. Drugs-Vehicles Congresses. I. Shalaby, Shalaby W. II. American Chemical Society. Meeting (185th: 1983: Seattle, Wash.) R857. P6P6 1985 610' .28 84-20666 ISBN-l3: 978-1-4612-9480-1 e-ISBN-13: 978-1-4613-2433-1 DOl: 10.1007/978-1-4613-2433-1 Proceedings of a symposium on Polymers as Biomaterials, held March 22-25, 1983, at the American Chemical Society meeting in Seattle, Washington © 1984 Plenum Press, New York Softcover reprint of the hardcover 1s t edition 1984 A Division of Plenum Publishing Corporation 233 Spring Street, New York, N. Y. 10 01 3 All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, micrafilming, recording, or otherwise, without written permission from the Publisher PREFACE Nearly 4000 years ago, the Egyptians used linen, a natural polymeric material, for suturing wounds. About 600 B.C., the Indians used other forms of natural polymers such as cotton, horse hair, and leather in repairing wounds. Wound closure procedures using silk sutures, based mostly on polypeptides, are likely to have been practiced during the second century. Surgical application of natural polymers continued to represent the major use of polymers until the twentieth century. Not too long after the development of several major synthetic polymers, their use in biomedical applications has attracted the attention of many re searchers and clinicians. Over the past few years, interest in the biomedical applications of polymers has grown considerably. This has been the result of the inevitable collaborative efforts of in novative materials scientists, engineers and clinicians. The es tablishment of the Society for Biomaterials, in our opinion, cata lyzed the growing interest in the use of polymers for biomedical application. In a major effort to bring team players even closer, a five-day symposium on "Polymers as Biomaterials" was held in Seattle, Washing ton, in March, 1983 as part of the national meeting of the American Chemical Society. The symposium was designed to provide a forum for communicating technical and clinical data to colleagues with a broad spectrum of interest in the biomedical applications of polymers. This volume represents most of the symposium proceedings and consists of six sections. Section A describes new and known poly meric materials and their physico-chemical properties as they pertain to specific biomedical applications. In Section B, some experimental aspects of surface characterization and interaction of blood com ponents with polymeric surfaces are documented. Interaction of polymeric materials with the biologic environment is used in Section C to demonstrate the response of polymeric materials to changes in the surrounding environment and biodegradation of synthetic polymers. Section D encompasses key interactions of the biologic environment with polymeric surfaces. Thus, the effects of surface properti es on v the behavior of living cells and certain cellular events are em phasized. Section E is dedicated to the role of polymers in the development of new, controlled drug delivery systems. The final section of this volume addresses the release kinetics and transport through hydrogels and the interaction of their hydrophilic surfaces with blood components and ionic species of the biologic environment. This book is designed and certainly hoped to be a valuble asset to investigators in academic, governmental, and industrial institutions who intend to be at the forefront of new technologies relevant to the development of new polymeric materials for known and novel biomedical applications. S.W. Shalaby A.S. Hoffman B.D. Ratner T.A. Horbett CONTENTS SECTION A MATERIALS & PROPERTIES Poly(p-Malic Acid) as a Source of Polyvalent Drug Carriers: Possible Effects of Hydrophobic Substituents in Aqueous Media . . . . . . . . . . . . . . . . . . . 1 Christian Braud and Michael Vert Polypentapeptide of Elastin as an Elastomeric Biomaterial 17 D. W. Urry, S. A. Wood, R. D. Harris and K. U. Prasad Development of Non-Thrombogenic Materials . . . . . . 33 J. L. Williams, A. Rumaks and J. P. O'Connell The Use of Polyacrylates in the Microencapsulation of Mammalian Cells .............. . 39 F. V. Lamberti, R. Evangelista, M. A. Wheatley, J. Blysniuk and M. V. Sefton Melt Spinning of Poly-L-Lactide and Hydrolysis of the Fiber In Vitro . . . . . . . ." ... 51 S.-H. Hyon; K. Jamshidi and Y. Ikada Some Morphological Investigations on an Absorbable Copolymer Biomaterial Based on Glycolic and Lactic Acid ........... . 67 Brandt K. Carter and Garth L. Wilkes Structural Identification of CIS-Platinum II Polyhydrazines ... .--.--. . . . . 93 C. E. Carraher, Jr., T. A. Manek, G. G. Hess, D. J. Giron, M. L. Trombley and R. J. Linville vii Flourescence in Polymers: 2-Diphenylacetyl-l, 3-Indanedione-l-Imine Derivatives in Polymer Matrices .... . . . . . . . . . 111 C. A. Byrne, E. J. Poziomek, O. I. Kutai, S. L. Suib and S. J. Huang SECTION B SURFACE CHARACTERISTICS An XPS and SEM Study of Polyurethane Surfaces: Experimental Considerations ...... . 121 R. W. Paynter, B. D. Ratner and H. R. Thomas Polymer Surfaces Possessing Minimal Interaction with Blood Components .............. . 135 Y. Ikada, M. Suzuki and Y. Tamada Thermodynamic Assessment of Platelet Adhesion to Polyacrylamide Gels . . . 149 D. R. Absolom, M. H. Foo, W. Zingg and A. W. Neumann SECTION C INTERACTION WITH THE BIOLOGIC ENVIRONMENT Reproducible Response of Certain Polymers to Changes in the Surrounding Environment ..... 167 Jorge Heller Mechanism of the Biodegradation of Polycaprolactone 181 P. Jarrett, C. V. Benedict, J. P. Bell, J. A. Cameron and S. J. Huang Swelling Behavior of Sensitive Membranes 193 Glu~ose T. A. Horbett. J. Kost and B. D. Ratner SECTION D BIOLOGICAL INTERACTIONS WITH POLYMERIC SURFACES Selected Aspects of Cell and Molecular Biology of In Vivo Biocompatibility .... 209 R. E. Marchant, K. M. Miller, A. Hiltner and J. M. Anderson Molecular Design of Materials Having an Ability to Differentiate Lymphocyte Subpopulations ... 225 Kazunori Kataoka viii Attachment of Staphylococci to Various Synthetic Polymers. 241 Anna Ludwicka, B. Jansen, T. Wadstrom, L. M. Switalski, G. Peters and G. Pulverer Blood Compatibility of Polyethylene and Oxidized Polyethylene in a Canine A-V Series Shunt: Relationship to Surface Properties .... 257 M. D. Lelah, C. A. Jordan, M. E. Pariso, L. K. Lambrecht, R. M. Albrecht and S. L. Cooper SECTION E DRUG DELIVERY SYSTEMS Polymer Based Drug Delivery: Magnetically Modulated and Bioerodible Systems . . . . . . . . . 279 E. R. Edelman, R. J. Linhardt, H. Bobeck, J. Kost, H. B. Rosen and R. Langer Oral Sustained Release Drug Delivery System Using Polymer Film Composites ...... . 293 Sumita B. Mitra Chemical Characterization of an Immobilized Heparin: Heparin - PVA . . . . . . . . . . . 305 Cynthia H. Cholakis and Michael V. Sefton Tumorcidal Activation and Kinetics of Ectoenzyme Production Elicited by Synthetic Polyanions. • • • • • • . • • •• 317 R. . M. Ottenbrite, K. R. Kuus and A. M. Kaplan SECTION F HYDROGELS A Responsive Hydrogel as a Means of Preventing Calcification in Urological Prostheses 323 E. C. Eckstein, L. Pinchuk and M. R. Van De Mark Potassium Ion Transport Through Membranes in the Presence of Blood Components: Plasma Proteins 333 G. S. Margules, J. A. Kane, A. R. Livingston and D. C. MacGregor Influence of Gel and Solute Structure on In Vitro and In Vivo Release Kinetics from Hydrogel~ .. 347 J. M. Wood, D. Attwood and J. H. Collett ix Interaction Between Blood Components and Hydrogels with Poly(Oxyethylene) Chains . . . . . . 361 S. Nagaoka, Y. Mori, H. Takiuchi, K. Yokota H. Tanzawa and S. Nishiumi Use of Methyl Cyanoacrylate (MCA) as a Sclerosing Agent in Female Sterilization: Effect of Inhibitors and Radioopaque Additives on MCA Polymerization In Vitro and on Oviduct Occlusion In Vivo in Rabbits ..... 375 James A. Nightingale, Allan S. Hoffman, Sheridan A. Halbert and Richard G. Buckles Index . . . . . . . . . . . . . . . . . . . . 387 x POLy(S-MALIC ACID) AS A SOURCE OF POLYVALENT DRUG CARRIERS: POSSIBLE EFFECTS OF HYDROPHOBIC SUBSTITUENTS IN AQUEOUS MEDIA Christian Braud and Michel Vert Universite de Rouen, ERA CNRS nO 471 LSM, INSCIR, BP 8, 76130 Mont Saint Aignan, France INTRODUCTION According to literature, the interest in investigating synthe tic macromolecular compounds for uses in biology and medicine is rapidely increasing. On one hand, attention has been focussed on polymer based implants for prostheses, tissue restauration and drug-delivery devices. In these cases, macromolecular compounds act, and sometimes react, as solids in the biological milieu. However, attention has been also payed to uses of synthetic polymers molecu larly dispersed in body fluids and, more generally, in the living medium. Two types of compounds have been considered : macromolecules that are pharmacologically active by themselves (polymeric drugs), and drug-polymeric carrier systems which bear drugs temporarily attached to the polymer backbone either covalently (macromolecular prodrugs) or because of physical interactions. It is of value to note that distinction between polymeric drugs and macromolecular prodrugs is based on expected uses. Indeed, it is likely that no macromolecule is inert in the living medium. A great number of biologically active macromolecular systems have been considered in the last three decades (1-7). However, the literature reveals primarily chemistry work, for the synthesis of of their properties. It is remarkable that only little has been made to investigate structure-activity relationships in detail though many authors early suspected the importance of structural features such as chain coiling and/or folding, tacticity, electrolytic character etc •.. (Donaruma (1), Kopecek (4), Ottenbrite (7)) in drug design work. In this respect, not very much more than what was known in 1974 (1) is available at the moment (8). There are many