Background: The treatment of extensive skin defects and bradytrophic wounds remains a challenge in clinical practice. Despite emerging tissue engineering approaches, skin grafts and dermal substitutes are still the routine procedure for the majority of skin defects. Here, we review the role of vascularization and lymphangiogenesis for skin grafting and dermal substitutes from the clinician’s perspective. Summary: Graft revascularization is a dynamic combination of inosculation, angiogenesis, and vasculogenesis. The majority of a graft’s microvasculature regresses and is replaced by ingrowing microvessels from the wound bed, finally resulting in a chimeric microvascular network. After inosculation within 48–72 h, the graft is re-oxygenated. In contrast to skin grafts, the vascularization of dermal substitutes is slow and dependent on the ingrowth of vessel-forming angiogenic cells. Preclinical angiogenic strategies with adipose tissue-derived isolates are appealing for the treatment of difficult wounds and may markedly accelerate skin reconstruction in the future. However, their translation from bench to bedside is still restricted by major regulatory restrictions. Finally, the lymphatic system contributes to edema reduction and the removal of local wound debris. Therapeutic lymphangiogenesis is an emerging field of research in skin reconstruction. Key Messages: For the successful engraftment of skin grafts and dermal substitutes, the rapid formation of a microvascular network is of pivotal importance. Hence, to understand the biological processes behind revascularization of skin substitutes and to implement this knowledge into clinical practice is a prerequisite when treating skin defects. Furthermore, a functional lymphatic drainage crucially contributes to the engraftment of skin substitutes.

Keywords:
Angiogenesis, Inosculation, Lymphatic system, Prevascularization, Skin graft, Skin substitute, Wound healing
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