The role of oxidation and enzymatic hydrolysis on the in vivo degradation of trimethylene carbonate based photocrosslinkable elastomers Rafi Chapanian a , M. Yat Tse b , Stephen C. Pang b , Brian G. Amsden a, * a Department of Chemical Engineering, Queen’s University, 19 Division Street, Dupuis Hall, Kingston, Ontario K7L 3N6, Canada b Department of Cell Biology and Anatomy, Queen’s University, 19 Division Street, Kingston, Ontario K7L 3N6, Canada article info Article history: Received 19 June 2008 Accepted 14 September 2008 Available online 23 October 2008 Keywords: In vivo degradation Enzymatic degradation Oxidative degradation Tissue response abstract The in vivo degradation of trimethylene carbonate (TMC) containing elastomers was investigated, and the mechanism of degradation explored through in vitro degradation under enzymatic and oxidative conditions. The elastomers were prepared via UV initiated crosslinking of prepolymers of TMC and equimolar amounts of TMC and 3-caprolactone (CL). The degradation process was followed by investi- gating the changes in the mechanical properties, mass loss, water uptake, sol content, differential scanning calorimetry, and surface chemistry through attenuated total reflectance infrared (ATR-FTIR) spectroscopy. During in vivo degradation, TMC and TMCCL elastomers exhibited surface erosion. The tissue response was of greater intensity in the case of the TMC elastomer. Both elastomers exhibited degradation in cholesterol esterase containing solutions in vitro, but no parallels were found between the rate of in vivo degradation and the rate of in vitro degradation. Only the TMCCL elastomer degraded in lipase. Degradation in a stable superoxide anion in vitro medium was consistent with the observed in vivo degradation results, indicating a dominant role of oxidation through the secretion of this reactive oxygen species by adherent phagocytic cells in the degradation of these elastomers. Ó 2008 Elsevier Ltd. All rights reserved. 1. Introduction Synthetic biodegradable elastomers based on trimethylene carbonate (TMC) are potentially useful materials in many biomedical applications, such as tissue engineering scaffolds and drug delivery [1]. Importantly, TMC based polymers degrade by surface erosion without producing acidic products [2], and thus could possibly be used to prepare more effective acid sensitive protein delivery systems. We are interested in the use of photo- cross-linked biodegradable elastomers prepared from u,u 0 ,u 00 -tri- acrylate star-poly(TMC) and star-poly(TMC-co-3-caprolactone) for this purpose. The in vivo mechanism of degradation of, and tissue reaction to, such implants are of great importance, as they provide an idea about the environment in which the therapeutic proteins are retained and eventually released. Upon implantation, a series of events occurs that results in monocytes moving from the blood to the implanted material surface. The monocytes adhere to the surface in a manner deter- mined by the type, concentration, and conformation of proteins adsorbed to the material surface. Within 48 h, monocytes are the predominant cell type at the biomaterial surface, and ultimately differentiate into monocyte-derived macrophages over a period of several weeks. On the surface, the macrophages spread and, as a result of frustrated phagocytosis, release reactive oxygen species as well as hydrolytic enzymes, and may fuse to form foreign body giant cells (FBGCs) [3]. FBGCs have an increased capacity for enzyme and reactive species secretion, and are longer lived than macrophages. The extent of monocyte adhesion and ultimately FBGC formation, as well as secretion capacity, have been shown to be determined by the chemistry of the material surface [4–7]. Thus, there are multiple possible degradation mechanisms for implanted polycarbonates, including acid–base catalyzed hydrolysis, as well as enzymatically catalyzed hydrolysis and oxidation from reactive oxygen species as a result of the response of phagocytic cells. The data to date indicate that acid or base catalyzed hydrolysis of the carbonate bonds plays a negligible role in in vivo degradation. Mizutani and Matsuda investigated the hydrolytic degradation of photo-cured poly(TMC) and copolymers of poly(TMC-co-3-capro- lactone) terminated with coumarin with different ratios of capro- lactone (CL) at pH values ranging from 7.4 to 10.2. They found that, irrespective of copolymer composition, hydrolysis occurred on the surface, and the rate of hydrolysis increased as pH and CL content increased [8]. However, when the elastomers were prepared from star -poly(trimethylene carbonate) triacrylate, negligible hydrolysis occurred [9]. This difference in degradation is likely due to the photo-reversibility of the [2 þ 2] cycloaddition linkage formed upon crosslinking with coumarin. Zhang et al. found that in in vitro environments with pH values ranging from 1 to 13, both high and * Corresponding author. E-mail address: brian.amsden@chee.queensu.ca (B.G. Amsden). Contents lists available at ScienceDirect Biomaterials journal homepage: www.elsevier.com/locate/biomaterials 0142-9612/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.biomaterials.2008.09.038 Biomaterials 30 (2009) 295–306