Chitosan/biphasic calcium phosphate composite scaffold incorporated with trichostatin a for bone regeneration

Abstract

This study synthesized a chitosan-based scaffold incorporated with trichostatin A (TSA), an epigenetic modifier molecule, using a freeze-drying technique to achieve promising bone regeneration potential. The scaffolds with various biphasic calcium phosphate (BCP) proportions: 0%, 10%, 20%, and 40% were characterized. The addition of BCP improved the scaffolds' mechanical properties and delayed the degradation rate. From all physicochemical parameters, 20% BCP scaffold matched the appropriate bone scaffold requirements and was selected for further development. The proper concentration of TSA was also tested. Our developed scaffold released TSA and sustained them for up to 3 days. The scaffold with 800 nM of TSA showed excellent biocompatibility and induced osteoblast-related genes expression in the primary human periodontal ligament cells (hPDLCs). To evaluate in vivo bone regeneration potential, the scaffolds were implanted in the mice calvarial defect model. The excellent bone regeneration ability of the CS/BCP/TSA scaffolds was further demonstrated in the micro-CT and histology sections compared to both negative control and commercial bone graft product. New bone formed in the CS/BCP/TSA group revealed a trabeculae-liked structure characteristic of the mature bone at both 6 and 12 weeks. The CS/BCP/TSA scaffold is an up-and-coming candidate for the bone tissue engineering scaffold.