Accelerating vascularization in skin composites

To date, engineered tissue substitutes do not contain a vascular plexus that would warrant graft survival and rapid integration into defected organs. Therefore, the engineering of stable blood vessels within the mesenchymal (stromal) component of a given tissue substitute represents a fundamental challenge.
Our goal is to develop epithelio-mesenchymal tissue substitutes, such as dermo-epidermal skin grafts, that have been pre-vascularized in vitro. We hypothesize that such a pre-vascularized graft would allow for a rapid connection to the patient’s vascular system after transplantation. As a consequence, the transplant (consisting of a significant cell mass) would be sufficiently supplied with nutrients and oxygen and also be better protected against infection.
The rationale that underlies this approach is based on the observation that full and split thickness skin grafts are rapidly vascularized and survive after transplantation. This is possible because the vascular plexus present in these skin grafts readily connects to the patient’s circulatory system and hence ascertains perfusion.
The physiological pattern of the vascular network of a tissue or organ is determined by the proliferation, branching, remodeling, and pruning of its different segments. The functionality and stability of blood vessels are determined by the ratio of endothelial cells to mural cells (pericytes, smooth muscle cells).
We have developed a procedure to isolate microvascular endothelial cells from human skin. In addition, we have created a biodegradable scaffold and culture conditions that optimally support the formation of three dimensional, lumen forming capillaries. We are currently testing the properties of pre-vascularized dermal substitutes in animal experiments.