Surface-decorated hydroxyapatite scaffold with on-demand delivery of dexamethasone and stromal cell derived factor-1 for enhanced osteogenesis

In the process of bone regeneration, relatively early biological events including inflammatory response, angiogenesis, or stem cell homing, help the accompanying target actions of cell differentiation and calcification. Herein, we proposed a novel cell-guided tissue engineering system based on a surface-functionalized porous hydroxyapatite (HA) scaffolds with the ability to recruit cells and accelerate the differentiation of them along the osteoblastic lineage for optimizing large-sized bone defect repair. Inspired by microstructural properties of natural bone, HA scaffolds similar to the trabecular bone structure were prepared via a sugar sphere leaching technique, in which the inter-pore opening size was controllable. Dexamethasone (Dex)-loaded hydroxypropyl-beta-cyclodextrin microspheres (Dex@CDMs) and stromal cell derived factor-1 (SDF-1) were uniformly immobilized onto HA surface by a cross-linked alginate coating. The resulting scaffold (SDF-1/Dex@CDMs-HA) enabled the on-demand dual-delivery of SDF-1 and Dex. In vitro cell culture assays showed that initially released SDF-1 markedly stimulated the migration of mesenchymal stem cells (MSCs) to the deep interior of the scaffold, providing abundant target cells for the function of Dex which was subsequently released. Osteogenic differentiation potential of these cells was also further facilitated via a synergistic action of SDF-1 and Dex. Additionally, in vivo studies demonstrated that the cell-guided system effectively improved the early cell recruitment and vascularization within the deep interior of scaffold and significantly accelerated the extensive formation of osteoid and mineralized tissue compared with the controls. Accordingly, such a microsphere coating-decorated multifunctional scaffold shows a promising potential for cell-free bone tissue engineering applications.