Biomimetic Chondroitin Sulfate–Hydroxyapatite Nanobiocomposites Functionalized with Thiol and Amine Moieties for Bone Tissue Regeneration and Oxidative Stress Alleviation

Abstract

Bone fracture repair remains a major clinical challenge, particularly under oxidative and inflammatory conditions that limit the therapeutic performance of conventional hydroxyapatite (HAP)-based biomaterials. To address these limitations, we developed bioinspired chondroitin sulfate (CS)-functionalized HAP nanobiocomposites with surface thiol (–SH) and amine (–NH₂) functionalities using a facile one-pot aqueous synthesis. This strategy enables simultaneous Ca²⁺-mediated HAP nucleation and CS incorporation, yielding hierarchically organised nanostructures with controlled molecular interfaces. Structural and physicochemical analyses confirmed the successful formation and chemical stability of the functionalized CS–HAP nanocomposites. The engineered materials exhibited excellent cytocompatibility toward MG-63 osteoblast like cells and effectively mitigated reactive oxygen species (ROS) induced apoptosis in the Drosophila melanogaster model. These findings demonstrate that the developed one-pot platform provides a promising strategy for engineering multifunctional, biomimetic, and osteoinductive nanoscaffolds capable of promoting bone regeneration while simultaneously alleviating oxidative stress in bone fracture microenvironments.