Three-dimensional electrospun nanofibrous scaffolds displaying bone morphogenetic protein-2-derived peptides for the promotion of osteogenic differentiation of stem cells and bone regeneration

[Display omitted] Tissue scaffolds with three-dimensional (3D) nanofibrous biomimetic structures have attracted attention in the field of bone regeneration. In recent years, emerging strategies based on electrospinning technologies have facilitated the preparation of 3D nanofibrous scaffolds. Based on these developments, in this study, 3D scaffolds possessing both nanofibrous morphologies and interconnected pores were fabricated for their potential in bone tissue engineering. By combining homogenizing, freeze-drying, and thermal crosslinking techniques, nano-hydroxyapatite/PLLA/gelatin (nHA/PLA/GEL) 3D nanofibrous scaffolds were prepared using pre-fabricated electrospun nanofibers. Then, utilizing a polydopamine (pDA)-assisted coating strategy, bone morphogenetic protein-2 (BMP-2)-derived peptides were further immobilized onto the 3D scaffolds to obtain the resulting nano-hydroxyapatite/PLLA/gelatin-peptide (nHA/PLA/GEL-PEP) 3D nanofibrous scaffolds capable of sustained release. Bone mesenchymal stem cells (BMSCs) were cultured on the 3D nanofibrous scaffolds, then relative cell viability, alkaline phosphatase (ALP) activity, and gene expression assays were performed to study the effects of the scaffolds on cell growth and osteogenic differentiation in vitro. Furthermore, the ability of bone formation in vivo was evaluated using a rat cranial bone defect model. In vitro and in vivo results demonstrated that the 3D nanofibrous scaffolds incorporated with nHA and BMP-2 peptides exhibited favorable biocompatibility and osteoinductivity. Therefore, these nanofibrous scaffolds have excellent potential in bone regenerative medicine.