Chitin nanowhiskers/octacalcium phosphate synergistically reinforced chitosan hydrogel for enhanced bone regeneration

Abstract The repair of jawbone defects faces critical challenges, such as the mechanical-bioactivity imbalance and limited bioactivity of traditional scaffold materials. This study proposes a “mechanical reinforcement–bio-mineralization” synergistic strategy to construct a chitin nanowhiskers (CHWs)/octacalcium phosphate (OCP) co-modified chitosan (CS) composite hydrogel (CS/CHWs-OCP) and systematically investigates its bone regeneration efficacy. Results demonstrate the successful fabrication of CS/CHWs-OCP hydrogels with gradient OCP loading (3%–12% wt). The hydrogels exhibit three-dimensional interconnected porous structures, favorable swelling properties, and effective protein loading/sustained-release capabilities. In vitro experiments reveal that CS/CHWs-OCPs significantly promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and angiogenic differentiation of EA.hy926 cells, with the 12 wt% OCP group showing the highest alkaline phosphatase (ALP) activity. Micro-CT 3D reconstruction and histological analysis demonstrate that the 12 wt% OCP group exhibits optimal calvarial defect repair capacity, with its new bone volume fraction (BV/TV: 57.2 ± 10.2%) at 8 weeks being significantly superior to both the blank control and OCP-free hydrogel groups. In conclusion, the developed CS/CHWs-OCP hydrogel provides an effective solution for bone defect regeneration.