Biomimetic mineralized hydrogels loaded with strontium-proanthocyanidins coordination particles for bone defect repair

Abstract Impaired vascularization and persistent inflammation strongly impede the healing of bone defects. To overcome these challenges, strontium-proanthocyanidins (PA) coordination particles (SrPA) with a particle size distribution of 600-900 nm were prepared. These SrPA particles were dispersed into sodium alginate (SA) solution pre-mixed with​ hydroxyapatite (HAp) and glutamate (Glu). A dual cross-linking process with HAp and Ca2+ increased the compressive strength of the resulting nnGS hydrogel by approximately 43-fold. As demonstrated by in vitro experiments, the release of PA from the nnGS modulated the inflammatory response and scavenged oxidative stress, whereas the release of Sr²⁺ promoted angiogenesis. Sr²⁺, PA, and Ca2+ may contribute to osteogenic differentiation, collectively influencing the expression of osteogenesis-related genes. The signaling pathways associated with osteogenesis and inflammation were the most enriched. The results of in vivo experiments indicated that the nnGS hydrogel promoted angiogenesis, modulated the inflammatory microenvironment, and accelerated bone repair at the defect site. By simultaneously addressing inflammation, vascularization, and osteogenic differentiation, this study provides a novel strategy for treating bone defects.