Dual-Functional Gel-Based Delivery of Chitosan-Coated Gold Nanoparticles for Accelerated Bone Healing in Defect...

Background: Effective management of bone defects remains a major clinical challenge, driving continuous efforts to develop bioactive, localized delivery systems that support bone regeneration. Gold nanoparticles (AuNPs) have gained attention in regenerative medicine for their capacity to modulate cellular activity. Yet, their application in functional delivery systems for bone repair is still limited. Chitosan (CS), a naturally derived biopolymer, exhibits notable osteoinductive properties, particularly when used to modify nanoparticulate carriers. Objectives: In this study, AuNPs and chitosan-coated gold nanoparticles (CS-AuNPs) were formulated, characterized, and incorporated into gel preparations to evaluate their physicochemical properties and therapeutic potential in a rat tibial bone defect model. Methods: AuNPs were synthesized and either left uncoated or coated with CS to enhance biological activity. Both formulations were examined for particle size, zeta potential, X-ray diffraction, and Fourier-transform infrared spectroscopy (FTIR). The resulting nanoparticles were integrated into gel bases, which were assessed for gel strength, swelling index, viscosity, and pH. The in vivo study involved surgically induced bone defects in the tibias of albino rats treated with either formulation. Healing outcomes were assessed via histological analysis, quantification of newly formed bone, immunohistochemical staining, radiographic imaging, and measurement of bone-related markers using RT-qPCR. Results: The CS-AuNP gel formulation demonstrated significantly improved bone regeneration compared to the uncoated counterpart, as evidenced by histological findings, increased bone volume in radiographs, stronger immunohistochemical expression of the VEGF angiogenic protein marker, and increased genetic expression of osteogenic markers. Conclusions: Incorporating CS-AuNPs into gel formulations offers a promising approach for enhancing bone healing. The superior performance of the CS-coated system highlights its potential as a promising localized therapy for managing bone defects.