Fibrin Hydrogels Prevent Contraction and Deliver Adipose Stem Cells to Debrided Deep Partial Thickness Burns for Accelerated Angiogenesis

Abstract

Autografts for wound coverage often have limited availability, and result in donor site morbidities. Many different tissue engineering strategies have been explored to minimize and/or circumvent the need for grafting, however none have proven adequate. One promising technologyis PEGylated fibrin (PEG‐fibrin) hydrogels that have previously been shown to deliver adipose‐derived stem cells (ASCs) for enhanced angiogenesis. Here, we investigate the effectiveness of the combination of ASCs and PEG‐fibrin hydrogels in a porcine model of debrided burn wounds. We hypothesized that the scaffolding provided by PEG‐fibrin would mitigate the contraction seen upon meshing of autografts, while ASC delivery would accelerate wound healing. Deep‐partial thickness burns were created on the dorsum of anesthetized Yorkshire pigs, and subsequently debrided on post‐injury day 4. After debridement, wounds were treated with: split thickness skin grafts (STSG);meshed STSG at 1:1.5 (mSTSG); and mSTSG + PEG‐fibrin with ASCs at 0, 1×105,5×105, and 1×106 cells per 3cm diameter wound. Photographs and biopsies were taken on post‐burn days 10, 14, 21, and 42, with euthanasiaon post‐burn day 42. Excised tissue was processed for routine histopathology and western blot analysis. Treatment with mSTSG resulted in significantly more contraction of wounds (88.9 ± 5.6 % of original area) compared to those treated with STSG (109.3 ± 5.0% of original area) and mSTSG + PEG‐fibrin (110.6 ± 6.9% of original area) out to day 42 post‐burn. When ASCs were delivered to the wounds in PEG‐fibrin, the size of blood vessels counted via histopathology on day 10post‐injury increased in a dose dependent fashion. Furthermore, the size oxblood vessels significantly correlated with CD31 protein levels (r=0.69, P<0.0042). Surprisingly, there was no effect on reepithelialization of the wounds. The current report describes a dual‐action adjunct therapy to autografting which can be administered in situ. Specifically, PEG‐fibrin hydrogels act not only as scaffolding, which prevents the ensuing contraction after skin autografts are meshed but also as delivery vehicles for ASCs, which ultimately accelerate angiogenesis in a dose‐dependent fashion. This platform may be used to deliver other cell types or growth factors for accelerating wound closure and improving wound outcomes. The ultimate goal in investigating the combination of ASCs and PEG‐fibrin is to generate vascularized skin equivalents to for enhanced graft integration and reduced scarring.Support or Funding InformationMedical Research and Materiel Command (MRMC) provided funding for this project.