Revascularization and angiogenesis for bone bioengineering in the craniofacial region: a review

The revascularization of grafted tissues is a complicated and non-straightforward process, which makes it challenging to perform reconstructive surgery for critical-sized bone defects. This challenge is combined with the low vascularity that results from radiotherapy. This low vascularity could result from ischemia-reperfusion injuries, also known as ischemia which may happen upon grafting. Ischemia may affect the hard tissue during reconstruction, and this can often cause resorption, infections, disfigurement, and malunion. This paper therefore reviews the clinical and experimental application of procedures that were employed to improve the reconstructive surgery process, which would ensure that the vascularity of the tissue is maintained or enhanced. It also presents the key strategies that are implemented to perform tissue engineering within the grafted sites aiming to optimize the microenvironment and to enhance the overall process of neovascularization and angiogenesis. This review reveals that the current strategies, according to the literature, are the seeding of the mature and progenitor cells, use of extracellular matrix (ECM), co-culturing of osteoblasts with the ECM, growth factors and the use of microcapillaries incorporated into the scaffold design. However, due to the unstable and regression-prone capillary structures in bone constructs, further research focusing on creating long-lasting and stable blood vessels is required.