Effect of Mixed Transplantation of Autologous and Allogeneic Microskin Grafts on Wound Healing in a Rat Model of Acute Skin Defect

Heng Lin,Daizhi Peng,Yanni Yang,Lihua Wang,Jing Liu,Yong Wang,Xin Zhou,Johanna M Brandner

doi:10.1371/journal.pone.0085672

Abstract

The treatment of extensive thermal injuries with insufficient autologous skin remains a great challenge to burn surgeons. In this study, we investigated the influence of the ratio of autologous and allogeneic tissue in mixed microskin grafts on wound healing in order to develop an effective method for using limited donor skin to cover a large open wound. Four different mixtures were tested: autologous microskin at an area expansion ratio of 10∶1 with allogeneic microskin at an area expansion ratio of 10∶1 or 10∶3 and autologous microskin at an expansion ratio of 20∶1 with allogeneic microskin at an expansion ratio of 20∶3 or 20∶6. Wound healing, wound contraction, and integrin β1 expression were measured. Mixed microskin grafting facilitated wound healing substantially. The mixture of autologous microskin at an expansion ratio of 10∶1 with the same amount of allogeneic microskin achieved the most satisfactory wound healing among the 4 tested mixtures. Histological examination revealed the presence of obviously thickened epidermis and ectopic integrin β1 expression. Keratinocytes expressing integrin β1 were scattered in the suprabasal layer. Higher levels of integrin β1 expression were associated with faster wound healing, implying that ectopic expression of integrin β1 in keratinocytes may play a pivotal role in wound healing. In conclusion, this study proves that this new skin grafting technique may improve wound healing.

Highlights

Closure of open wounds in the treatment of extensive thermal injury with insufficient autologous skin has been a great challenge to burn surgeons
The available methods of skin grafting remain limited to techniques including intermingled skin grafting using autologous skin islets inlaid in an allogeneic skin sheet [1], autologous microskin transplantation overlaid with viable allograft or xenograft skin [2], and in vitro cultured keratinocyte grafts [3]
Because no autologous microskin was used in group I, an adverse phenotype was observed in which the entire wound was filled with granulation tissue, with some de novo epithelium appearing at the wound edge, accompanied by shedding of the grafted allogeneic microskin from 2 to 4 PGWs (Figure 3A)

Summary

Introduction

Closure of open wounds in the treatment of extensive thermal injury with insufficient autologous skin has been a great challenge to burn surgeons. Its main advantages are that the autologous keratinocytes can induce local tolerance to allograft or xenograft tissue [1,4], which delays graft rejection, and that the autologous epithelium infiltrates quickly between the epidermis and dermis of the allograft or xenograft skin. This type of skin grafting requires 2-stage surgery, first burn eschar excision and coverage of the defect with allogeneic or xenogeneic skin followed by insertion of small autologous skin sheets into the allogeneic skin 3–6 days after the first surgery. This approach imposes the stress of surgery twice within a short time and results in extensive scarring after wound healing

Methods

Results

Conclusion