A scaffold with zinc-whitlockite nanoparticles accelerates bone reconstruction by promoting bone differentiation and angiogenesis

The therapy of bone defects based on advanced biological scaffolds offers the most promising therapeutic strategy for bone reconstruction. It is still challenging to develop scaffolds with the mechanical, osteogenic, angiogenic, and antibacterial properties required for bone defect reconstruction. Here, a novel organic/inorganic composite scaffold (zinc-whitlockite (ZnWH)/G/H) was synthesized using gellan gum (GG), human-like collagen (HLC), and ZnWH nanoparticles. The scaffold had excellent mechanical properties, adjustable swelling ratio, and interconnected pore structure. In addition to its excellent biocompatibility, it could promote osteogenic differentiation by releasing ZnWH nanoparticles to stimulate human bone marrow mesenchymal stem cells (hBMSCs) to upregulate the levels of alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). In addition, this study showed that ZnWH nanoparticles could also promote angiogenesis by upregulating the paracrine secretion of vascular endothelial growth factor (VEGF) in hBMSCs. At the same time, the scaffold could inhibit the proliferation of bacteria. After 12 weeks of treatment in the rabbit femoral defect model, the ZnWH/G/H scaffold significantly accelerated the process of bone reconstruction. Therefore, these results demonstrate that the prepared novel nanocomposite scaffold, ZnWH/G/H, offers a promising candidate for bone regeneration.