FGF-7 expression enhances the performance of bioengineered skin.
To improve the performance of bioengineered skin, we used a recombinant retrovirus encoding FGF-7 to modify diploid human keratinocytes genetically. Control or FGF-7-expressing keratinocytes were seeded onto acellular human dermis to form bioengineered skin. Gene-modified skin secreted significant levels of FGF-7 and formed a thicker and hyperproliferative epidermis with about four times the number of cells per square centimeter. Secretion of an endogenous trophic factor, VEGF, was increased approximately 5-fold. Migration of FGF-7-expressing keratinocytes was stimulated as was the self-healing of bioengineered skin expressing FGF-7. When tested in a bacterial infection model, the antimicrobial properties of FGF-7-expressing skin were increased >500-fold against both gram-negative and gram-positive bacteria. After transplantation to full-thickness wounds on athymic mice, skin expressing FGF-7 was revascularized more rapidly. These results demonstrate that genetic modification can be used to enhance performance and that expression of FGF-7 augments several properties important to the wound-healing properties of bioengineered skin.
Erdag
Gulsun
G
Center for Engineering in Medicine and Surgery, Massachusetts General Hospital and Harvard Medical School and Shriners Hospital for Children, Boston, MA 02114, USA.
Medalie
Daniel A
DA
Rakhorst
Hinne
H
Krueger
Gerald G
GG
Morgan
Jeffrey R
JR
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism; D001424:Bacterial Infections / Q000378:metabolism; D002465:Cell Movement; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D015316:Genetic Therapy; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D051379:Mice; D018919:Neovascularization, Physiologic; D012190:Retroviridae / Q000235:genetics; D012867:Skin / Q000166:cytology / Q000378:metabolism; D016038:Skin Transplantation / Q000379:methods*; D023822:Tissue Engineering / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing
D023181:Antimicrobial Cationic Peptides; C496453:FGF7 protein, human; C496454:Fgf7 protein, mouse; D042461:Vascular Endothelial Growth Factor A; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors