Differential acceleration of healing of surgical incisions in the rabbit gastrointestinal tract by platelet-derived growth factor and transforming growth factor, type beta.
Anastomotic dehiscence is a major cause of morbidity and mortality in gastrointestinal surgery. A unique model system of a gastric incision was developed to test the potential of polypeptide growth factors to enhance wound healing. Paired, deep partial-thickness incisions to but not including the gastric mucosa were made. A single topical application of transforming growth factor, type beta 1 (TGF-beta), platelet-derived growth factor, or control vehicle at the time of wounding was given. Wound breaking strength and detailed histologic analyses of wounds were evaluated as a function of time after wounding. TGF-beta (0.1 to 2.0 micrograms/wound) demonstrated a bimodal, dose-dependent acceleration of wound breaking strength 7 days after gastric wounding. An approximate 4-day acceleration of gastric wound breaking strength by TGF-beta (2 micrograms/wound) was seen at 7 and 11 days. Wounds treated with platelet-derived growth factor (10 micrograms/wound) displayed an increased cellular response but no enhancement of breaking strength at 7 and 11 days. These results demonstrate the ability of TGF-beta to accelerate gastrointestinal tissue repair by topical application and suggest significant potential for the use of growth factors in enhancing repair of surgical wounds of the gastrointestinal tract.
Mustoe
T A
TA
Department of Surgery, Washington University Medical Center, St. Louis, Mo.
Landes
A
A
Cromack
D T
DT
Mistry
D
D
Griffin
A
A
Deuel
T F
TF
Pierce
G F
GF
D000818:Animals; D004068:Digestive System Physiological Phenomena; D013505:Digestive System Surgical Procedures; D004305:Dose-Response Relationship, Drug; D005260:Female; D005753:Gastric Mucosa / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011817:Rabbits; D013997:Time Factors; D015291:Transforming Growth Factors / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
D010982:Platelet-Derived Growth Factor; D015291:Transforming Growth Factors