Crosslinking chitosan with glucose via the modified Maillard reaction promotes the osteoinduction of mouse MC3T3-E1 pre-osteoblasts

Bone defects are a common clinical issue, but therapeutic efficiency can be challenging in cases of more considerable traumas or elderly patients with degenerated physiological metabolism. To address this issue, a more suitable cell-biomaterial construct promoting bone regeneration has been extensively investigated, with the chitosan scaffold being considered a potential candidate. In this study, chitosan was crosslinked with different doses of glucose (CTS-10~50%Glc) using a modified Maillard reaction condition to develop a more appropriate cell-biomaterial construct. Mouse MC3T3-E1 pre-osteoblasts were seeded onto the scaffolds to examine their osteoinductive capability. The results showed that CTS-Glc scaffolds with higher glucose contents effectively improved the adhesion and survival of mouse MC3T3-E1 pre-osteoblasts and promoted their differentiation and mineralization. It was further demonstrated that the membrane integrin α5 subunit of pre-osteoblasts is the primary adhesion molecule that communicates with CTS-Glc scaffolds. After that, Akt signaling was activated, and then bone morphogenetic protein 4 was secreted to initiate the osteoinduction of pre-osteoblasts. The prepared CTS-Glc scaffold, with enhanced osteoinduction capability and detailed mechanism elucidations, offers a promising candidate material for advancing bone tissue engineering and clinical regenerative medicine. As a result, this study presents a potential tool for future clinical treatment of bone defects.