Resurreccion-Magno, Maria Hanshella C.. Optimization of tyrosine-derived polycarbonate terpolymers for bone regeneration scaffolds. Retrieved from https://doi.org/doi:10.7282/T3GM86BN
DescriptionTyrosine-derived polycarbonates (TyrPC) are a versatile class of polymers highly
suitable for bone tissue engineering. Among the tyrosine-derived polycarbonates,
poly(DTE carbonate) has an FDA masterfile that documents its biocompatibility and nontoxicity and has shown potential utility in orthopedics due to its osteoconductive properties and strength. DTE stands for desaminotyrosyl-tyrosine ethyl ester and is the most commonly used tyrosine-derived monomer. However, in vitro degradation studies showed that poly(DTE carbonate) did not completely resorb even after four years of incubation in phosphate buffered saline. Thus for bone regeneration, which only requires a temporary implant until the bone heals, poly(DTE carbonate) would not be the best choice. The goal of the present research was to optimize a scaffold composition for bone regeneration that is based on desaminotyrosyl-tyrosine alkyl ester (DTR), desaminotyrosyl-tyrosine (DT) and poly(ethylene glycol) (PEG). Five areas of research were presented: (1) synthesis and characterization of a focused library of TyrPC terpolymers; (2) evaluation of the effects of how small changes on the composition affected the mechanism and kinetics of polymer degradation and erosion; (3) fabrication
of bioactive three-dimensional porous scaffold constructs for bone regeneration; (4)
assessment of osteogenic properties in vitro using pre-osteoblasts; and (5) evaluation of bone regeneration potential, with or without recombinant human bone morphogenetic protein-2 (rhBMP-2), in vivo using a critical sized defect (CSD) rabbit calvaria (cranium) model. Small changes in the composition, such as changing the R group of DTR from ethyl to methyl, varying the mole percentages of DT and PEG, and using a different PEG block length, affected the overall properties of these polymers. Porous scaffolds were prepared by a combination of solvent casting, porogen leaching and phase separation techniques. Calcium phosphate was coated on the surface post-fabrication. The scaffolds displayed (i) a bimodal pore architecture with micropores (< 20 μm) and macropores (200 – 400 μm), (ii) a highly interconnected and open pore structure, and (iii) a highly organized microstructure. These scaffolds supported robust cell attachment and promoted
osteogenic differentiation of pre-osteoblasts. This is the first report that a synthetic
polymeric scaffold either without a biological supplement or with a minimal dose of
rhBMP-2 induced comparable bone regeneration to a commercially available bone
substitute in a non-rodent CSD animal model.