Transforming growth factor-beta2 (TGF-beta2) reverses the inhibitory effects of fibrin sealant on cutaneous wound repair in the pig.
Tensile strength of 2-cm, full-thickness, surgically incised porcine skin wounds sealed with fibrin sealant was enhanced compared to conventionally sutured wounds at 6 hours postwounding, but was significantly reduced after 3 days. Supplementation of fibrin sealant with transforming growth factor-beta2 (TGF-beta2) reversed the inhibitory effects of fibrin sealant on tensile strength at 3 days, and enhanced tensile strength at 7 days compared to suture or fibrin sealant alone. By 14 days, the tensile strengths of all wounds were similar, although wounds treated with fibrin sealant supplemented with TGF-beta2 showed a small, but statistically significant, improvement in wound strength compared to wounds treated with fibrin sealant alone. Histological assessment at day 7 revealed significant remnants of fibrin sealant at the wound site following fibrin sealant treatment alone, while wounds treated with fibrin sealant supplemented with TGF-beta2 or suture exhibited fibroblast infiltration and extracellular matrix deposition. At day 7, TGF-beta was immunolocalized in the base and margins of only wounds treated with fibrin sealant supplemented with TGF-beta2. A significant increase in matrix metalloproteinase-9 activity was found in fibrin sealant-treated wounds at day 7 as compared to sutured wounds. Addition of TGF-beta to the fibrin sealant suppressed the up-regulation of matrix metalloproteinase-9 in these wounds. These results suggest that fibrin sealant supplemented with TGF-beta may provide superior wound healing as compared to fibrin sealant alone.
Center for Pediatric Urology and Laboratory for Minimally Invasive Urologic Surgery, Children's Hospital of New York, Weill Medical College of Cornell University, New York, New York, USA.
Peter B
PB
Petratos
Diane
D
Felsen
Grant
G
Trierweiler
Bruce
B
Pratt
John M
JM
McPherson
Dix P
DP
Poppas
D000818:Animals; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D015718:Fibrin Tissue Adhesive / Q000008:administration & dosage / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012867:Skin / Q000187:drug effects / Q000293:injuries* / Q000503:physiopathology*; D013552:Swine; D013718:Tensile Strength / Q000187:drug effects / Q000502:physiology; D014014:Tissue Adhesives / Q000008:administration & dosage / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D053781:Transforming Growth Factor beta2; D017211:Treatment Failure; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*; D014950:Wounds, Penetrating / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*
D015718:Fibrin Tissue Adhesive; D007166:Immunosuppressive Agents; D014014:Tissue Adhesives; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2