Bioinspired hydroxyapatite nanoparticle: Functionalization with chondroitin sulfate-thiol/amine moieties for synergistic bone tissue regeneration and oxidative stress mitigation.

Bone fractures remain a formidable clinical challenge, particularly in oxidative and inflammatory microenvironments where conventional hydroxyapatite (HAP)-based scaffolds exhibit poor redox buffering, limited biointeractivity, and suboptimal integration with native extracellular matrix (ECM) signaling pathways. In order to address these multifactorial limitations, we report the rational design and one-pot synthesis of bioinspired nanocomposites comprising chondroitin sulfate (CS)-functionalized HAP, which is further engineered with surface-exposed thiol (-SH) or amine (-NH₂) group. This aqueous-phase synthesis simultaneously orchestrates Ca2-templated HAP nucleation and CS conjugation, enabling hierarchical assembly with molecular level interface control. Comprehensive spectroscopic and microscopic analyses validate the formation of structurally coherent, chemically stable CS-HAP nanocomposites with post-synthetic -SH and -NH₂ functionalization. The developed nanobiocomposites exhibit enhanced cytocompatibility in the MG-63 osteoblast-like cell line and effectively attenuate ROS induced apoptosis in the Drosophila melanogaster model. This one-pot synthesis strategy presents a unified platform for engineering biomimetic and osteoinductive nanoscaffolds with dual functionality, supporting bone regeneration while concurrently serving as potent antioxidant candidates. The approach holds significant translational potential for therapeutic application in oxidative stress associated bone fracture microenvironments.