Carboxymethyl chitosan-alginate enhances bone repair effects of magnesium phosphate bone cement by activating the FAK-Wnt pathway.

Abstract

There is a continuing need for artificial bone substitutes for bone repair and reconstruction, Magnesium phosphate bone cement (MPC) has exceptional degradable properties and exhibits promising biocompatibility. However, its mechanical strength needs improved and its low osteo-inductive potential limits its therapeutic application in bone regeneration. We functionally modified MPC by using a polymeric carboxymethyl chitosan-sodium alginate (CMCS/SA) gel network. This had the advantages of: improved compressive strength, ease of handling, and an optimized interface for bioactive bone in-growth. The new composites with 2% CMCS/SA showed the most favorable physicochemical properties, including mechanical strength, wash-out resistance, setting time, injectable time and heat release. Biologically, the composite promoted the attachment and proliferation of osteoblast cells. It was also found to induce osteogenic differentiation in vitro, as verified by expression of osteogenic markers. In terms of molecular mechanisms, data showed that new bone cement activated the Wnt pathway through inhibition of the phosphorylation of β-catenin, which is dependent on focal adhesion kinase. Through micro-computed tomography and histological analysis, we found that the MPC-CMCS/SA scaffolds, compared with MPC alone, showed increased bone regeneration in a rat calvarial defect model. Overall, our study suggested that the novel composite had potential to help repair critical bone defects in clinical practice.