Restoration of critical defects in the rabbit mandible using osteoblasts and vascular endothelial cells co-cultured with vascular stent-loaded nano-composite scaffolds

Abstract

The success of large bone defect repair with tissue engineering technology depends mainly on angiogenesis and osteogenesis. In this study, we prepared poly-caprolactone/nano-hydroxyapatite/beta-calcium phosphate (PCL/nHA/β-TCP) composite scaffolds loaded with poly-(lactic-co-glycolic acid)/nano-hydroxyapatite/collagen/heparin sodium (PLGA/nHA/Col/HS) nanofiber small vascular stent by electrospinning and hot press forming-particle leaching methods. Supramolecular electrostatic self-assembly technology was used to modify the surfaces of small vascular stents to aid in hydrophilicity and anticoagulation. The surfaces of composite scaffolds were modified with an Arg-Gly-Asp (RGD) short peptide by physical adsorption to supply cell adhesion sites. The scaffolds were then combined with rabbit bone marrow-derived osteoblasts (OBs) and rabbit bone marrow-derived vascular endothelial cells (RVECs) to construct large, biologically active vascularized tissue-engineered bone in vitro; this bone was then used to repair critical bone defects in rabbit mandibles. Mechanical and biocompatibility testing results showed that PCL/nHA/β-TCP composite scaffolds loaded with small vascular stents had good surface structure, mechanical properties, biocompatibility, and bone-regeneration induction potential. Twelve weeks after implantation, histological analysis and X-ray scans showed that the use of osteoblasts and vascular endothelial cells co-cultured with PCL/nHA/β-TCP scaffolds was sufficient to repair critical defects in rabbit mandibles.

Keywords: Bone tissue engineering; Osteoblasts; Scaffold; Vascular endothelial cells; Vascularization.