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

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 calcium (Ca²⁺) increased the compressive strength of the resulting SrPA/HAp/glutamate/SA (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 strontium (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.