In vivo degradation behavior of PDC multiblock copolymers containing poly( p -dioxanone) hard segments and crystallizabl

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1190-NN06-05

In vivo degradation behavior of PDC multiblock copolymers containing poly(p-dioxanone) hard segments and crystallizable poly(ε-caprolactone) switching segments B. Hiebl1,2, K. Kratz1,2, R. Fuhrmann3, F. Jung1,2, A. Lendlein1,2, R-P. Franke1,2,3 1 Center for Biomaterial Development, Institute of Polymer Research, GKSS Research Center, Kantstrasse 55, D-14513 Teltow 2 Berlin-Brandenburg-Center for Regenerative Therapies, Charité- Universitätsmedizin Berlin_ BCRT, Campus Virchow-Klinikum, Augustenburger Platz 1, D-13353 Berlin 3 University of Ulm, Central Institute for Biomedical Engineering, Department of Biomaterials, Ulm, Germany

ABSTRACT The degradation behavior of biodegradable multiblock copolymers (PDC) containing poly(p-dioxanone) hard segments (PPDO) and crystallizable poly(ε-caprolactone) switching segments (PCL) synthesized via co-condensation of two oligomeric macrodiols with an aliphatic diisocyanate as junction unit was explored in in vivo and in vitro experiments. The in vitro experiments for enzymatic degradation resulted that the poly(ε-caprolactone) segments are degraded faster, than the poly(p-dioxanone) segments. During degradation the outer layer of the test specimen becomes porous. Finally non-soluble degradation products in form of particles were found at the surface. This observation is in good agreement with the in vivo studies, where the non-soluble degradation products in the periimplantary tissues showed a diameter of 1 – 3 micron.

INTRODUCTION For medical applications of hydrolytically degradable biomaterials like surgical implants, e.g. sutures, or implantable drug depots e.g. for treatment of cancer, a detailed knowledge of the degradation behaviour during use in patient is required. A major limitation of established degradable biomaterials like poly(α-hydroxy esters) is the fact, that their degradation behaviour during clinical application can not be predicted reliably based on the results of in vitro experiments [1]. Therefore more fundamental research is required to enable a knowledge based approach for biomaterial development. Multiblock copolymers with shape-memory capability attracted tremendous interest as promising candidates for enabling new medical applications like an intelligent surgical suture [2-6]. In the present work we investigated the degradation behavior of PDC multiblock copolymers, containing poly(p-dioxanone) hard segments (PPDO) and crystallizable poly(ε-caprolactone) switching segments (PCL). These copolyesterurethanes were synthetised by co-condensation of two oligomeric macrodiols with an aliphatic diisocyanate [4,6]. The PDC multiblock copolymers exhibited a linear mass loss during hydrolytic degradation experiments, whereby the rate of the mass loss was dependent on the PPDO content [4]. In PCL selective enzymatic degradation studies using Pseudomonas lipase [7,8] selectivity of the enzyme towards the degradation of the PCL-segments lead to increased degradation rates

in case of higher PCL-contents. In this study, the in vivo degradation behav