Engineered Biomaterials for Tissue Regeneration of Innervated and Vascularized Tissues: Lessons Learned from the Brain.

Spontaneous healing and recovery of innervated and vascularized tissues are limited. In particular, the complexity of the central nervous system's anatomy, physiology, and pathobiology make efforts to develop effective therapeutic strategies exceptionally challenging. Repairing the brain after injury implies restoring the tissue architecture of the neural and vascular networks both morphologically and functionally. The substantial clinical burden and disability after a central nervous system injury urges the need to explore therapeutic solutions outside the confine of conventional approaches used in regenerative medicine. Recent advances in tissue engineering and material sciences have developed biomimetic materials that can be injected or implanted directly to the site of damage to provide physical support to cell infiltration and growth, promoting tissue development and de novo formation of vascular and axonal networks through cell transplantation and/or controlled release of bioactive cues. These approaches have shown promise in promoting the endogenous repair machinery of the brain and controlling the growth and development of functional vascular and neural networks in the lesion to promote long-term functional recovery. This narrative review presents a comprehensive look at recent advances using proangiogenic engineered materials and drug delivery systems for brain repair after stroke.