Transforming Growth Factor β3 Promotes Fascial Wound Healing in a New Animal Model

Abstract

Transforming growth factor ␤ 3 (TGF-␤ 3) promotes fascial wound healing in a new animal model, as measured by wound breaking strength, collagen deposition, and cellular proliferation. Design/Intervention: Bilateral, longitudinal incisions were made in the anterior rectus sheaths of 24 male New Zealand white rabbits. One incision was treated with 1 µg of TGF-␤ 3 ; the contralateral incision served as a control. The wounds were harvested at 1, 2, 3, 4, 6, and 8 weeks after creation ("wounding"). Main Outcome Measures: Wound tissue was tested for breaking strength using a tensiometer and processed for histological examination of collagen deposition and cellular proliferation at all time points after wounding. Collagen deposition and cellular proliferation were measured in histological cross sections of wounds with Masson trichrome staining and proliferating cell nuclear antigen immunohistochemistry, respectively. Results: At all time points after wounding, treatment with TGF-␤ 3 significantly increased the wound breaking strength (up to 138%) and collagen deposition (up to 150%) over the control group. Cellular proliferation was increased during the first 3 weeks after wounding (up to 147%), but returned to baseline levels by the fourth week. Conclusions: Transforming growth factor ␤ 3 promotes fascial wound healing. In this new animal model of fascial wound healing, TGF-␤ 3 increased fascia breaking strength, collagen deposition, and cellular proliferation. These results are similar to findings in cutaneous wound models and demonstrate, for the first time, a pharmacologic agent to accelerate fascial healing.

The Role of TGFβ Signaling in Wound Epithelialization

“…1 It has been suggested that TGFb3 supports scarless wound healing through modulation of the inflammatory response and the recruitment of fibroblasts to the wound site while simultaneously enhancing keratinocyte migration. 21 Even though all three TGFb isoforms bind to the same receptors, their effects may be different depending on genetic milieu and environment of the target cell. 5 In vitro, TGFb1 clearly promotes keratinocyte migration by increasing the expression of different integrins, which, in turn, promotes the adhesion and migration of keratinocytes.…”

An Experimental Animal Model for Abdominal Fascia Healing after Surgery

“…Most existing IH models have used rats, but both rabbits and dogs have also been used to produce experimental IH [31,32]. The majority of the existing models has been developed to investigate IH and is based on roughly the same surgical procedure as in the present model with a paramedian skin incision and a median fascial incision [12,13,14,15,17,18,19].…”

Avotermin: A Novel Antiscarring Agent

“…Administration of TGFβ3 to wounds in animals has been shown to both accelerate healing and increase tissue strength in adult models. [69][70][71] It is also important to demonstrate in a clinically relevant model that the treatment has no adverse effects on wound healing (ie, is safe, well tolerated, and does not impair normal wound healing) and that systemic exposure (bioavailability) is limited at concentrations exceeding those that will be used in humans. To this end, we have recently developed a model of 20-cm full-thickness, sutured cutaneous incisional wounds in the Gottingen Minipig.…”