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.
Petratos
Peter B
PB
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.
Felsen
Diane
D
Trierweiler
Grant
G
Pratt
Bruce
B
McPherson
John M
JM
Poppas
Dix P
DP
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