Synthesis, degradation and biocompatibility of tyrosine-derived polycarbonate scaffolds

Polycarbonate terpolymers consisting of desaminotyrosyl-tyrosine alkyl esters (DTR), desaminotyrosyl-tyrosine (DT), and low molecular weight blocks of poly(ethylene glycol) (PEG) are a new class of polymers that have good engineering properties while also being resorbable in vivo. This study is the first evaluation of their (i) degradation behavior, (ii) in vitro cytotoxicity, and (iii) in vivo biocompatibility. Porous, tissue engineering scaffolds were prepared by a combination of solvent casting, porogen leaching and phase separation techniques. The scaffolds (>90% porosity) displayed (i) a bimodal pore distribution with micropores of less than 20 µm and macropores between 200 and 400 µm, (ii) a highly interconnected and open pore architecture, and (iii) a highly organized microstructure where the micropores are oriented and aligned along the walls of the macropores. Molecular weight (number average, Mn) and mass loss were determined in vitro (PBS at 37 °C) for up to 28 days. All three terpolymer compositions were fast degrading and retained only 10% of their initial molecular weight after 21 days, while mass loss during the 28 days was polymer composition-dependent. In vitro biocompatibility of the polymer scaffolds was determined up to 14 days by measuring metabolic activity of MC3T3.E1 (subclone 4) pre-osteoblasts. The outcome showed no statistical difference between cells cultured in monolayer and all tested polymer scaffolds. Robust cell attachment throughout the scaffold volume was observed by confocal microscopy and SEM. The biocompatibility of resorbing scaffolds was evaluated at 12 week in a critical sized defect (CSD) rabbit calvaria model and showed only a minimal inflammatory response. Overall, the results reported here illustrate the potential utility of tyrosine-derived polycarbonate terpolymers in the design of tissue engineering scaffolds.