Enzyme Degradable Networks Prepared from a Poly(trimethylene Carbonate)-Peptide Biohybrid

Abstract

The main objective of this thesis was to develop a biohybrid network with appropriate mechanical properties for a range of soft connective tissue engineering applications that could be degraded solely by the action of the target enzymes. An α-vinyl sulfone (VS), ω-methacrylate (MA) heterobifunctional poly(trimethylene carbonate) (PTMC)/ poly(ethylene glycol) (PEG)-PTMC was prepared and conjugated to a di-cysteine containing matrix metalloproteinase (MMP)-sensitive peptide to form a curable prepolymer. These biohybrid formulations were designed to be cured via a simplified one-step cross-linking process by having both the synthetic polymer and the MMP-sensitive peptide components in a single prepolymer. The degradation behavior and the change in moduli were assessed for the biohybrid networks in vitro using a proteinase-containing medium and in vivo using a Wistar rat model. Both studies confirmed the enzyme degradation of the biohybrid networks via the cleavage of the peptide component and the hydrolytic resistance of the synthetic polymer backbone and the thio-ether linkage over the experimental time frame. The new formulation may be able to support the lost or damaged soft connective tissue mechanically, with identical mechanical features, until the healing process is completed. In addition, a moderate tissue response was observed to the implanted biohybrid networks which was comparable to that observed towards a VicrylTM suture. This observation suggested that these new materials can be considered biocompatible for tissue engineering applications. Overall, the developed biohybrid formulation has shown promising in vitro and in vivo degradation and mechanical properties that would be suitable for soft connective tissue engineering.