title: Bioengineered skin allografts: a new method to prevent humoral response.
abstract: 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.
authors.affiliation: Department of Plastic and Reconstructive Surgery, University Medical Center Utrecht, Utrecht, The Netherlands. lbrasile@citlink.net
authors.forename: Lauren
authors.initials: L
authors.lastname: Brasile
authors.forename: Philip
authors.initials: P
authors.lastname: Glowacki
authors.forename: Bart M
authors.initials: BM
authors.lastname: Stubenitsky
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D057005:Bioengineering; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000276:immunology; D016220:Fibroblast Growth Factor 1 / Q000008:administration & dosage; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D056724:Immunity, Humoral; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008422:Materials Testing; D008567:Membranes, Artificial; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D049329:Nanostructures; D011994:Recombinant Proteins / Q000008:administration & dosage; D016038:Skin Transplantation / Q000276:immunology* / Q000379:methods*; D014184:Transplantation, Homologous
chemical_list: D008567:Membranes, Artificial; D011994:Recombinant Proteins; D016220:Fibroblast Growth Factor 1