Strategies to Induce Blood Vessel Ingrowth into Skin Grafts and Tissue-Engineered Substitutes

Skin is a multilayer organ consisting of several tissues and appendages residing in a complex niche. Adequate and physiologically regulated vascularization is an absolute requirement for skin homeostasis, regeneration, and wound healing. The lack of vascular networks and ischemia results in delayed wound closure. In addition, vascularization is critical for the prolonged function and survival of skin grafts and tissue-engineered skin substitutes. This study highlights the clinical challenges associated with the limited vascularization in the cutaneous wounds. Then, we highlight the novel approaches for the development of vascular networks in the skin autografts, allografts, and artificial substitutes. Also, the future directions to overcome the existing vascularization complications in skin grafting and synthetic skin substitutes are presented. Statement of SignificanceDelayed closure of large dermal wounds, such as burn injuries, results from the lack of vascular networks and ischemia. The amount of blood supply in the skin graft is the primary factor determining the quality of the transplanted grafts. The current skin grafts and their fabrication methods lack the appropriate features that contribute to the vascularization and integration of the wound bed and graft and adherence to the skin layers. Therefore, the new generation of skin grafts should consider advanced technologies to induce vascularization and overcome current challenges.