Multifactor, Sequentially Releasing Scaffolds for Tissue Engineering:Fabrication Using Solvent/Nonsolvent Sintering Technology

Biodegradable constructs, providing both mechan- ical support to growing tissues and timed release of biologi- cal agents, are highly desired in tissue engineering. This study aimed to develop a platform technology that responds to these challenges. Accordingly, we report herein on model systems in which microspheres of poly(suberic anhydride), containing all-trans retinoic acid (atRA), and poly(d,l-lactic acid-co-glycolic acid), containing bovine serum albumin (BSA), were co-sintered at room temperature, using a sol- vent/nonsolvent mixture. These scaffolds release about 60% of atRA and negligible amounts of BSA within the first five days, followed by slower and steady release of BSA. They have pores of 150-500 mm and a compressive modulus of 200 kPa. Myoblasts and fibroblasts were seeded on the loaded scaffolds and both showed enhanced proliferation rates. Based on sound thermodynamic principles of polymer science, this technology demonstrates an as yet unachieved degree of versatility. It allows for the tailoring of "intelligent" scaffolds that preserve the integrity of the incorporated agents and of advanced modalities to release various drugs in a scheduled manner.