Carboxymethyl chitosan-enhanced multi-level microstructured composite hydrogel scaffolds for bone defect repair

Abstract

Critical-sized bone defects (CSBDs) necessitate interventions like bone grafts or tissue engineering scaffolds to surpass the body's limited spontaneous healing capacity and ensure effective bone regeneration. A multi-level microstructured composite hydrogel 3D scaffold was fabricated for enhanced bone defect repair, integrating a 3D-printed macroporous polylactic acid (PLA) scaffold with polydopamine treatment and filled with a sodium alginate/nano hydroxyapatite/carboxymethyl chitosan (SA/nHA/CMCS) micrometer-scale porous composite hydrogel. The incorporation of nano hydroxyapatite (nHA) nanoparticles enhanced hydrogel crosslinking and osteogenic activity. A systematic evaluation of CMCS concentration demonstrated its pivotal role in enhancing hydrogel cross-linking and mineralization, regulating degradation rate adapted to the osteogenic cycle, endowing the scaffold with a bioactive micrometer-scale porous structure. In vitro studies confirmed the osteogenic effectiveness of the composite hydrogel 3D scaffold, particularly those with CMCS, which boosted bone mesenchymal stem cells (BMSCs) adhesion, proliferation, and differentiation. The rabbit tibial bone defect model further confirmed that, compared to the DAPLA (dopamine modified PLA) scaffold, the bone trabecular number of the DSHC (DAPLA-SA/nHA/CMCS) scaffold increases 2.06-fold. In conclusion, this study expanded the application of hydrogel scaffolds in bone tissue engineering and provided an effective strategy for the development of hydrogel implant materials.