Single-stage transplantation combined with epidermal stem cells promotes the survival of tissue-engineered skin by inducing early angiogenesis

Abstract

Background The composite transplantation of a split-thickness skin graft (STSG) combined with an acellular dermal matrix (ADM) is a promising repair method for full-thickness skin defects. Due to delayed vascularization of the ADM, no currently available engineered skin tissue is able to permanently cover full-thickness skin defects via a single-stage procedure. Epidermal stem cells (EpSCs) have been found to promote angiogenesis in the wound bed. Whether EpSCs can induce early angiogenesis of dermal substitutes and promote the survival of single-stage tissue-engineered skin transplantation needs to be further studied. Methods In vitro, rat vascular endothelial cells (RVECs) were treated with the supernatant of EpSCs cultured in ADM and stimulated for 48 h. RVECs were analysed by RNA sequencing and tube formation assays. For the in vivo experiment, 75 rats were randomly divided into five groups: ADM, ADM + EpSCs (AE), STSG, ADM + STSG (AS), and ADM + STSG + EpSCs (ASE) groups. The quality of wound healing was estimated by general observation and H&E and Masson staining. The blood perfusion volume was evaluated using the LDPI system, and the expression of vascular markers was determined by immunohistochemistry (IHC). Results The active substances secreted by EpSCs cultured in ADM promoted angiogenesis, as shown by tube formation experiments and RNA-seq. EpSCs promoted epithelialization of the ADM and vascularization of the ADM implant. The ASE group showed significantly increased skin graft survival, reduced skin contraction, and an improved cosmetic appearance compared with the AS group and the STSG control group. Conclusions In summary, our findings suggest that EpSCs promote the formation of new blood vessels in dermal substitutes and support one-step transplantation of tissue-engineered skin, and thereby provide new ideas for clinical application.

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“…The main disadvantage of STSGs is that they are more fragile and have a high chance of shrinking. 18 The cause for the disadvantages is the lack of dermis taken from the donor section. Despite all the shortcomings STSGs remain the doctors' first choice for most skin graft procedures.…”

“…Despite all the shortcomings STSGs remain the doctors' first choice for most skin graft procedures. 18 Exciting new research is currently being conducted with STSGs to help make skin grafts more durable for patients. The research involves combining STGS with an acellular dermal matrix (ADM) to remove the previous constraints STSGs had.…”

“…The experiment showed that the combination of STSGs, ADM, and EpSCs in mice can do a onestep repair on a full-thickness wound with little shrinkage and more durability. 18…”