Development and Characterization of a Bioactive Injectable Chitosan Hydrogel for Bone Repair

Clinical needs of bone and cartilage grafting for the reconstruction of trauma, chronic diseases and congenital anomalies are substantial. Injectable and biodegradable hydrogels are potential candidates as cell delivery vehicles to support tissue regeneration. The intrinsic properties of glycol-chitosan such as aqueous solubility, biocompatibility, enzymatic degradability, and antibacterial activity make it one of the most preferred natural polymers as scaffolds for tissue engineering. In our studies, we describe the synthesis and characterization of enzymatically cross-linkable glycol-chitosan hydrogel as an injectable minimally-invasive cell and drug delivery vehicle. The results showed the ability of the hydrogel to maintain the viability and morphology of encapsulated ATDC-5 chondrocyte cells. We further demonstrated the ability of the gels to locally release bone morphogenetic protein (BMP-2) in a bioactive form to induce significant bone formation at the site of implantation using a mouse calvarial defect model. We further investigated increasing the bioactivity of the injectable gel by incorporating statin, an FDA approved drug which is known to show anabolic effect towards bone, even though the exact molecular mechanism is not clearly understood. We demonstrated the feasibility of incorporating statins in the injectable glycol-chitosan gels and our pilot in vivo study demonstrated the potential osteogenic properties of the statin conjugated injectable gels.