Research ArticleBioengineering

Bioengineering Dermo-Epidermal Skin Grafts with Blood and Lymphatic Capillaries

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Science Translational Medicine  29 Jan 2014:
Vol. 6, Issue 221, pp. 221ra14
DOI: 10.1126/scitranslmed.3006894

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Skin Grafts Need Plumbing, Too

To help heal a severe burn or wound, clinicians surgically transplant skin grafts, which consist of the epidermis (outer skin layer) and, often, part of the dermis (deeper layer, directly below the epidermis). The success of these grafts, however, is limited by the ability of blood vessels to form in the newly transplanted skin and deliver nutrients to the cells. Research has also suggested that the lymphatics may be necessary for skin graft survival, by essentially draining immune cells, debris, and excess fluid from the wounded area. Here, Marino, Luginbühl, and colleagues engineered a skin graft that wasn’t just the patient’s skin cells—it also contained both lymph and blood capillaries “prevascularized” ex vivo and then transplanted onto a wound.

The authors created the dermo-epidermal skin grafts by taking cells from human foreskin, called human dermal microvascular endothelial cells (HDMECs), and embedding them in three-dimensional hydrogels. HDMECs consist of a mixture of both lymphatic endothelial cells and blood vessel endothelial cells, so both types of functional capillaries—blood and lymph—formed from these cells in vitro in the fibrin or collagen hydrogels. Moving in vivo, the authors transplanted engineered skin grafts containing the HDMECs as well as human fibroblasts and keratinocyes—two cell types found in skin—onto the wounded backs of nude rats (animals without an immune system). Marino, Luginbühl, et al. reported that the human skin grafts formed the expected skin layers after 2 weeks, connected with existing rat lymphatic capillaries, and drained fluid away from the wound.

Although testing and characterization are still needed in animals with an immune system and with skin similar to humans (such as a pig), these engineered dermo-epidermal hydrogels potentially represent the next generation of skin grafts, complete with the vascular and lymphatic plumbing and ready to transplant.

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