Bioengineered Skin Allografts: A New Method To Prevent Humoral Response

We previously reported that a bioengineered interface consisting of a nano-barrier membrane (NB-LVF4) used as an artificial interface between skin allografts and wound surfaces significantly prolonged graft survival without immunosuppression. We now evaluated whether NB-LVF4 could serve as a targeted drug delivery system to further improve outcomes. Fibroblast growth factor-1 (FGF-1) was selected for its known function as a wound hormone. Full-thickness 8-mm skin grafts were cross-transplanted between out-bred mice. Controls were transplanted without treatment. In test groups, the NB-LVF4, with or without FGF-1, was applied to both basolateral skin and wound surfaces with polymerization resulting in a tridimensional transparent membrane. The mice were evaluated for T-cell activation and development of donor-specific antibody. Rejection occurred in controls by 7 days. NB-LVF4 treatment, with or without FGF-1, was found to significantly prolong allograft survival (27 and 28 days, respectively [p < 0.05]). Untreated controls stimulated 10-fold shift in the number of circulating CD4+ cells while test groups exhibited substantially reduced shifts in CD4+ cells. The group treated with FGF-1 did not develop donor-specific antibody. Treatment with the NB-LVF4 membrane delays the onset of allograft rejection in the absence of systemic immunosuppression. FGF-1 appears to prevent the development of a humoral response by preventing B cell activation.