Mechanical strategies to promote vascularization for tissue engineering and regenerative medicine

Vascularization is a major challenge in the field of tissue engineering and regenerative medicine. Mechanical factors have been demonstrated to play a fundamental role in vasculogenesis and angiogenesis and can affect the architecture of the generated vascular network. Through the regulation of mechanical factors in engineered tissues, various mechanical strategies can be used to optimize the preformed vascular network and promote its rapid integration with host vessels. Optimization of the mechanical properties of scaffolds, including controlling scaffold stiffness, increasing surface roughness and anisotropic structure, and designing interconnected, hierarchical pore structures, is beneficial for the in vitro formation of vascular networks and the ingrowth of host blood vessels. The incorporation of hollow channels into scaffolds promotes the formation of patterned vascular networks. Dynamic stretching and perfusion can facilitate the formation and maturation of preformed vascular networks in vitro. Several indirect mechanical strategies provide sustained mechanical stimulation to engineered tissues in vivo, which further promotes the vascularization of implants within the body. Additionally, stiffness gradients, anisotropic substrates and hollow channels in scaffolds, as well as external cyclic stretch, boundary constraints and dynamic flow culture, can effectively regulate the alignment of vascular networks, thereby promoting better integration of prevascularized engineered tissues with host blood vessels. This review summarizes the influence and contribution of both scaffold-based and external stimulus-based mechanical strategies for vascularization in tissue engineering and elucidates the underlying mechanisms involved.