Role of biomechanics in vascularization of tissue-engineered bones

Biomaterial based reconstruction is still the most commonly employed method of small bone defect reconstruction. Bone tissue-engineered techniques are improving, and adjuncts such as vascularization technologies allow re-evaluation of traditional reconstructive methods for healingofcritical-sized bone defect. Slow infiltration rate of vasculogenesis after cell-seeded scaffold implantation limits the use of clinically relevant large-sized scaffolds. Hence, in vitro vascularization within the tissue-engineered bone before implantation is required to overcome the serious challenge of low cell survival rate after implantation which affects bone tissue regeneration and osseointegration. Mechanobiological interactions between cells and microvascular mechanics regulate biological processes regarding cell behavior. In addition, load-bearing scaffolds demand mechanical stability properties after vascularization to have adequate strength while implanted. With the advent of bioreactors, vascularization has been greatly improved by biomechanical regulation of stem cell differentiation through fluid-induced shear stress and synergizing osteogenic and angiogenic differentiation in multispecies coculture cells. The benefits of vascularization are clear: avoidance of mass transfer limitation and oxygen deprivation, a significant decrease in cell necrosis, and consequently bone development, regeneration and remodeling. Here, we discuss specific techniques to avoid pitfalls and optimize vascularization results of tissue-engineered bone. Cell source, scaffold modifications and bioreactor design, and technique specifics all play a critical role in this new, and rapidly growing method for bone defect reconstruction. Given the crucial importance of long-term survival of vascular network in physiological function of 3D engineered-bone constructs, greater knowledge of vascularization approaches may lead to the development of new strategies towards stabilization of formed vascular structure.