Angiogenesis in Bone Tissue Engineering

Abstract

Received: Septenber 25, 2018; Accepted: October 18, 2018; Published: October 24, 2018 Blood vessel formation is described by two distinct mechanisms called vasculogenesis and angiogenesis [1]. During vasculogenesis, the first primitive vascular plexus and the heart form inside the developing embryo and new blood vessels arise out of mesodermal-derived hemangioblasts. Angiogenesis is defined as the formation of new blood vessels out of the existing vasculature in order to support vascular network expansion and remodelling. Network expansion is based on endothelial cell proliferation, migration and tube formation [2]. Since the passive transport by diffusion of oxygen and nutrients is limited by tissue thickness, a blood vessel is necessary every 100-200 μm to support active nutrient supply and waste product removal [3]. Tissue supply with nutrients through blood vessels is not only important for organ homeostasis, it is also necessary for tissue regeneration and wound healing, which are important elements addressed in bone tissue engineering (BTE). Bone is an adult tissue that has the ability to heal itself when a specific size is not exceeded (so called critical size defect). However, the healing can be disturbed, making bone reconstruction after trauma impossible. Reconstructive surgical therapies currently use autologous, allogeneic and synthetic materials to fill the bone defects [4]. Autologous bone replacement is the gold standard in term of osteoinduction and osteoconduction. A disadvantage is that it is only available in limited amounts and in addition to the surgical intervention for defect reconstruction an additional surgery is required to obtain the autologous bone from the patient [5]. In comparison to autologous grafts, allografts are available in much higher quantities and shapes. However, they have a lower osteoinductivity compared to autologous grafts, which can lead to worse healing compared to autologous grafts. Thus, synthetic grafts like for example ceramics, metals or polymers are considered for BTE [5–7]. In contrast to autologous grafts, synthetic grafts do not provide the cellular elements necessary for osteogenesis and therefore exhibit lower osteoinductivity than autologous bone substitutes [8]. Since decades, insufficient vascularization hinders the translation of engineered bone constructs into the clinics. In addition, support of a bone environment rich in vascular networks is important for the tissue integration and its functionality after bone graft implantation [9] underlining the important role of angiogenesis and endothelial cells in BTE. Approaches discussed in the literature to increase vascularization include seeding cells on bone grafts and the control and guidance of vascular structure growth [10].