Enhanced tissue infiltration and bone regeneration through spatiotemporal delivery of bioactive factors from polyelectrolytes modified biomimetic scaffold

Efficient healing of bone defect is closely associated with the structured and functional characters of tissue engineered scaffolds. However, the development of bone implants with rapid tissue ingrowth and favorable osteoinductive properties remains a challenge. Herein, we fabricated polyelectrolytes modified-biomimetic scaffold with macroporous and nanofibrous structures as well as simultaneous delivery of BMP-2 protein and trace element strontium. The hierarchically structured scaffold incorporated with strontium-substituted hydroxyapatite (SrHA) was coated with polyelectrolyte multilayers of chitosan/gelatin via layer-by-layer assembly technique for BMP-2 immobilization, which endowed the composite scaffold with sequential release of BMP-2 and Sr ions. The integration of SrHA improved the mechanical property of composite scaffold, while the polyelectrolytes modification strongly increased the hydrophilicity and protein binding efficiency. In addition, polyelectrolytes modified-scaffold significantly facilitated cell proliferation in vitro, as well as enhanced tissue infiltration and new microvascular formation in vivo. Furthermore, the dual-factor loaded scaffold significantly enhanced the osteogenic differentiation of bone marrow mesenchymal stem cells. Moreover, both vascularization and new bone formation were significantly increased by the treatment of dual-factor delivery scaffold in the rat calvarial defects model, suggesting a synergistic effect on bone regeneration through spatiotemporal delivery of BMP-2 and Sr ions. Overall, this study demonstrate that the prepared biomimetic scaffold as dual-factor delivery system has great potential for bone regeneration application.