Background
Bone injury is a common surgical disease. Smaller bone injuries can heal on their own, but larger bone defects often cannot heal on their own. Tissue engineering technology provides a new approach to bone repair, but after bone repair material transplantation, host blood is difficult to penetrate into the scaffold, resulting in insufficient local blood supply, so its repair effect is still inferior to that of autologous bone. Angiogenesis plays an important role in bone development and reconstruction. Therefore, in addition to the osteogenic properties of bone tissue engineering scaffold materials, their vascularization is also an important factor in promoting bone defect repair.
Vascularization and Osteogenesis Mechanism
Vascular endothelial growth factor (VEGF) can effectively promote angiogenesis. At the same time, VEGF is also an important active factor involved in the bone repair process. It can participate in the bone repair process by affecting the complex interaction between vascular endothelial cells and osteoblasts. However, the effective activity and long-term release of VEGF restrict its application in tissue engineering. Bone injury will lead to insufficient blood supply to the injured site, thus forming a hypoxic microenvironment at the injured site. The hypoxic microenvironment at the injured site can indirectly promote osteogenesis by upregulating the expression of VEGF in the tissue through the production of HIF-1α, promoting VEGF-mediated vascularization. The hypoxic environment can reduce the expression of intracellular osteogenic induction factors such as alkaline phosphatase (ALP) and osteocalcin (OCN), and HIF-1α can promote the osteogenic differentiation of cells in a hypoxic environment to a certain extent. HIF-1α is continuously expressed, but it is rapidly degraded under normoxic conditions. One of the main enzymes involved in its degradation process is prolyl hydroxylase domain (PHD). It has been reported that inhibiting PHD activity can increase the expression level of endogenous HIF-1α. Currently, among many PHD inhibitors, dimethyloxallyl glycine (DMOG) has good angiogenic properties and low biological toxicity, so it can be used as a good angiogenic drug for vascular regeneration. Previous studies have shown that stabilizing the expression of HIF-1α can effectively promote angiogenesis. Moreover, compared with VEGF, DMOG is not easy to inactivate and has a lower cost, and has greater application potential. Electrospinning technology is a technology that can prepare polymer materials with micro-nano structures, and it is widely used in the field of tissue engineering. The biological scaffold material prepared by electrospinning technology has an extremely high specific surface area and porosity. The prepared spinning fiber can stimulate the secretion of extracellular matrix by loading different drugs or growth factors, thereby facilitating cell adhesion, proliferation and specific differentiation.
Figure 1. Sequence of fabrication of artery-like tubular tissues with PLCL scaffolds. (Y. Yamagishi, et al.; 2014)
Function of PLCL Electrospun Fibres
Polylactic acid-ε-caprolactone (PLCL) is an aliphatic polyester, also known as poly-L-lactide-caprolactone and polylactide-caprolactone. It is a linear polymer copolymer obtained by ring-opening polymerisation of caprolactone and lactic acid, which can be divided into two types: random copolymers and block copolymers. Polylactic acid-ε-caprolactone (PLCL) has the advantages of controllable degradation rate, high flexibility, adjustable elasticity, adjustable tensile strength, excellent biocompatibility, biodegradability, non-toxic degradation products and drug permeability. It can be used in tissue engineering, surgical sutures, drug delivery and other fields. PLCL has been approved for clinical use by the US Food and Drug Administration (FDA). Therefore, some researchers prepared PLCL electrospun fibers by electrospinning technology and used them to load DMOG for continuous controlled release of drugs to achieve osteogenesis by promoting vascularisation. The results showed that the electrospun fibres prepared in this study had a good pore structure. The electrospun fibres loaded with DMOG can also promote the expression of vascularisation-related genes VEGF, thus effectively promoting vascularisation. Therefore, the electrospun fibres prepared with the participation of PLCL are beneficial to promote osteogenesis and angiogenesis in the hypoxic environment of bone injury, thus having better bone repair potential. The biological scaffold material prepared with the participation of PLCL has good biocompatibility and in vitro osteogenesis performance, and can be used as an excellent bone repair material for bone tissue engineering.
References
- Sivaraj KK, Adams RH. Blood vessel formation and function in bone. Development. 2016, 143(15): 2706-2715.
- Greenhill C. Formation of blood vessels in bone maturation and regeneration. Nat Rev Endocrinol. 2014, 10(5): 250.
- Y. Yamagishi, et al.; Microfluidic perfusion culture system for artery-like tubular tissues with PLCL scaffolds. 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences. 2014, 978-0-9798064-7-6.
