Cancellous Bone‐Like Sr‐Doped Hydroxyapatite/Gelatin Porous Scaffolds With Nanofibrous Architecture and Ion Release for Promoting Osteogenesis

ABSTRACT Constructing a porous scaffold with the essential features of natural cancellous bone, including structural architecture and biochemical cues, is one of the pivotal factors for effective bone regeneration. In this study, a biomimetic composite porous Gelatin fibrous scaffold (SrHA/Gelatin) incorporating ultralong strontium‐doped hydroxyapatite nanofibers was fabricated via thermally induced phase separation and paraffin sphere leaching technologies. The porous scaffold exhibited an interconnected macroporous network with a fibrous framework. SrHA nanofibers incorporated into the scaffold created an extracellular matrix‐like microenvironment although simultaneously providing excellent elasticity, mechanical resilience, and abundant sites for cell anchoring. Importantly, substitution of Ca 2+ by Sr 2+ in the hydroxyapatite (HA) crystal lattice accelerated nanofiber degradation and enabled the sustained release of Ca 2+ and Sr 2+ ions, thereby establishing a dynamic osteoinductive microenvironment. In vitro studies showed that the SrHA/Gelatin scaffold significantly enhanced adhesion, proliferation, and migration of bone marrow mesenchymal stem cells, as well as upregulated expression of the osteogenic gene compared with Gelatin and HA/Gelatin scaffolds. Furthermore, in vivo experiments revealed that the scaffold induced robust trabecular bone formation and defect bridging in rat calvarial defects, whereas only limited repair was observed in the control group. This study demonstrates that the SrHA/Gelatin porous scaffold integrates mechanical robustness, structural biomimicry, and dynamic ionic release, representing a promising candidate for bone defect repair.