Vascularization strategies for bone regeneration.

The functional regeneration of thick vascularized tissues such as bone and muscle is complicated by the large volume of lost tissue, challenging biomechanical environment, and the need to reproduce the highly organized structure of both the native tissue extracellular matrix and its vascular support system. Stem cell or progenitor cell delivery approaches, for example, continue to be plagued by low viability and engraftment in part due to the initial absence of a vascular supply. Recognition of diffusion limitations in thick tissues has prompted regenerative strategies that seek to accelerate establishment of a functional vasculature. The successful design of robust regeneration strategies for these challenging clinical scenarios will rely on a thorough understanding of interactions between construct design parameters and host biological and biomechanical factors. Here, we discuss the critical role of vascularization in normal bone tissue homeostasis and repair, vascular network adaptation to the local biomechanical environment, and the future directions of revascularization approaches being developed and integrated with bone regeneration strategies.