Injectable polysaccharide-based composite hydrogel promotes regeneration of critical-sized bone defects

Critical-sized bone defects (CSDs) fail to undergo spontaneous regeneration. Conventional treatment methods, including bone grafts, as well as therapies based on growth factors and cytokines often face serious limitations, including limited availability, immune rejection, high cost, and safety concerns. Although tissue engineering using scaffolds has emerged as a promising alternative, many scaffold-based approaches still rely on the incorporation of exogenous growth factors or cytokines to achieve adequate osteoinductive performance, adding complexity, cost, and potential safety concerns to the treatment. Moreover, invasive implantation techniques and use of toxic crosslinkers during scaffold fabrication present additional challenges. Herein, we report the development of a minimally invasive, injectable, and fully biocompatible hydrogel (CCD@HapSi). The hydrogel, formed via a simple Schiff-base reaction between carboxymethyl chitosan and oxidized dextran, incorporates nanohydroxyapatite and silica nanoparticles to impart osteoinductive, osteoconductive, and antibacterial functionality without the need for external crosslinkers or growth factors. CCD@HapSi exhibited ultrafast gelation, optimal mechanical strength, and controlled degradation, while supporting stem cell adhesion, proliferation, and upregulation of osteogenic genes. In vivo, the hydrogel promoted substantial bone regeneration in a critical sized calvarial defect, significantly outperforming control groups. These findings highlight CCD@HapSi as a safe, cost-effective, and clinically translatable platform for bone regeneration.