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

Abstract

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.