Within the vascular endothelial growth factor (VEGF) family of five subtypes, VEGF165 secreted by endothelial cells has been identified to be the most active and widely distributed factor that plays a vital role in courses of angiogenesis, vascularization and mesenchymal cell differentiation. Hair follicle stem cells (HFSCs) can be harvested from the bulge region of the outer root sheath of the hair follicle and are adult stem cells that have multi-directional differentiation potential. Although the research on differentiation of stem cells (such as fat stem cells and bone marrow mesenchymal stem cells) to the endothelial cells has been extensive, but the various mechanisms and functional forms are unclear. In particular, study on HFSCs' directional differentiation into vascular endothelial cells using VEGF165 has not been reported. In this study, VEGF165 was used as induction factor to induce the differentiation from HFSCs into vascular endothelial cells, and the results showed that Notch signalling pathway might affect the differentiation efficiency of vascular endothelial cells. In addition, the in vivo transplantation experiment provided that HFSCs could promote angiogenesis, and the main function is to accelerate host-derived neovascularization. Therefore, HFSCs could be considered as an ideal cell source for vascular tissue engineering and cell transplantation in the treatment of ischaemic diseases.

Dense biomaterial plays an important role in bone replacement. However, it fails to induce bone cell migration into graft material. In the present study, a novel bone graft substitute (BGS) consisting of porous gradient hydroxyapatite/zirconia composite (PGHC) and gelatin/chitosan slow-release hydrogel containing bone morphogenetic protein 2 and bone mesenchymal stem cells was designed and prepared to repair lumbar vertebral defects. The morphological characteristics of the BGS evaluated by a scanning electron microscope showed that it had a three-dimensional network structure with uniformly distributed chitosan microspheres on the surfaces of the graft material and the interior of the pores. Then, BGS (Group A), PGHC (Group B), or autologous bone (Group C) was implanted into lumbar vertebral body defects in a total of 24 healthy rhesus monkeys. After 8 and 16 weeks, anteroposterior and lateral radiographs of the lumbar spine, microcomputed tomography, histomorphometry, biomechanical testing, and biochemical testing for bone matrix markers, including Type I collagen, osteocalcin, osteopontin, basic fibroblast growth factor, alkaline phosphatase, and vascular endothelial growth factor, were performed to examine the reparative efficacy of the BGS and PGHC. The BGS displayed excellent ability to repair the lumbar vertebral defect in rhesus monkeys. Radiography, microcomputed tomography scanning, and histomorphological characterization showed that the newly formed bone volume in the interior of the pores in the BGS was significantly higher than in the PGHC. The results of biomechanical testing indicated that the vertebral body compression strength of the PGHC implant was lower than the other implants. Reverse-transcription polymerase chain reaction and western blot analyses showed that the expression of bone-related proteins in the BGS implant was significantly higher than in the PGHC implant. The BGS displayed reparative effects similar to autologous bone. Therefore, BGS use in vertebral bone defect repair appears promising.

New porous gradient hydroxyapatite/zirconia composites can promote the repair of bony defect, and induce bone tissue to ingrow into the pores, which may be applied widely to the treatment of bony defect in the future.

The goals of bone tissue engineering are to apply biomaterial scaffolds with adhered cells, such as osteoblasts, bone marrow stromal stem cells, or chondrocytes, to repair, regenerate, and restore the functions of damaged bone tissue or to replace those tissues with porous engineered biomaterials. Over recent decades, a diverse class of biomaterials has been applied in bone tissue engineering field. Porous hydroxyapatite bioceramic is currently receiving significant attention as a bone tissue engineering substitute because of its biological characteristics, including biocompatibility, bioactivity, osteoconduction, and vasculogenesis. This biomaterial has a three-dimensional structure with interconnected spherical pores of uniform size, which encourages bone ingrowth and achieves good integration of the material and the host bone over time. However, the compressive strength and elastic modulus of porous hydroxyapatite scaffolds generally weaken as the porosity increases, in both in vitro and in vivo testing. Zirconia can be used to toughen hydroxyapatite materials for bone repair and replacement because of its unique biomechanical properties, including compressive strength and fracture toughness. Additionally, a zirconia chitosan hybrid containing bone morphogenetic protein-2 and mesenchymal stem cells derived from induced pluripotent stem cells has been used as a coating material adhered to surface of scaffolds to promote bone regeneration and repair. Here, we provide a succinct review of zirconia toughened hydroxyapatite biomaterial scaffolds that incorporate bone morphogenetic protein-2 and mesenchymal stem cells for bone tissue engineering and describe the biomaterials that are currently being investigated based on the recent literature and our own data.