Efficacy of growth factors in the accelerated closure of interstices in explanted meshed human skin grafts.

Meshed split-thickness skin grafts, especially when required to be widely spread, do not obtain immediate biologic wound closure. In cases of patients with burns that cover a large percentage of the body surface area, this leaves the patient at risk for metabolic problems and life-threatening infection. Several cytokines and growth factors could theoretically affect the rate of epithelialization and, therefore, the rate of meshed graft interstitial closure. With the use of human meshed skin grafts explanted onto athymic "nude" rats, the epithelialization kinetics of interleukin-4 (IL-4), macrophage colony-stimulating factor (MCSF), keratinocyte growth factor-1 (KGF-1), keratinocyte growth factor-2 (KGF-2), basic fibroblast growth factor (bFGF), and transforming growth factor beta-2 (TGF(B2)) were investigated; the results were compared with the rates of epithelialization of grafts treated with a vehicle control. On postoperative day 3, wounds treated with IL-4, KGF-2, bFGF, and TGF(B2) showed a significantly increased rate of interstitial closure (P < .05). On postoperative days 5 and 7, wounds treated with KGF-2, bFGF, and TGF(B2) all exhibited a significantly higher rate of interstitial closure than the grafts in the control group (P < .05). These data suggest that epithelialization kinetics can be accelerated with the use of several topical growth factors, and they provide support for a future clinical trial.

The effect of TGF-beta2 in various vehicles on incisional wound healing.

BACKGROUND: The isoforms of transforming growth factor beta (TGF-beta) have been shown to be deficient in models of impaired wound healing. Exogenous application of the growth factor to enhance healing as been investigated. TGF-beta1 has been shown to enhance incisional wound strength, but to be dependent on the vehicle used to carry the cytokine. Because TGF-beta2 has shown safety in human trials of chronic wound healing, this study evaluates TGF-beta2 in acute incisional healing using a variety of vehicles. METHODS: Using an acute incisional wound model in healthy rats, rhTGF-beta2 was suspended in various vehicles including fibrin sealant (normal commercial concentration), fibrin sealant (dilute concentration), phosphate buffered saline/serum albumin, and a carboxymethycellulose gel. A single dose of the agent was instilled into the incisions at the time of wound closure and breaking strength analyses and histology performed periodically from days 3-14. RESULTS: TGF-beta2 enhanced the gain of incisional strength in all vehicles during the first two weeks of healing. This was most noticeable by day three with the carboxymethycellulose gel, but by day 7 with the other vehicles. Like reports with TGF-beta1, TGF-beta2 accelerated the gain of wound strength by about three days by day 11. Normal density fibrin sealant delayed incisional healing; whereas, the other vehicles without TGF-beta2 had no significant effect. CONCLUSIONS: The use of TGF-beta2 appears to be of value in increasing incisional wound strength in the first 14 days post-wounding in healthy rats and this effect is demonstrated in a variety of vehicles. These data support the hypothesis that the "normal" incisional wound healing curve can he shifted to the left. Shortening the time for gain of incisional wound strength may have potential clinical use.

In vivo characterization of keratinocyte growth factor-2 as a potential wound healing agent.

Human keratinocyte growth factor-2 exerts a proliferative effect on epithelial cells and mediates keratinocyte migration. It has also been shown to increase both deposition of granulation tissue and collagen and maturation of collagen. Because these properties should affect the healing trajectory of wounds, this study set out to investigate the effects of keratinocyte growth factor-2 on the healing of three different types of wounds. Human meshed skin grafts explanted to athymic "nude" rats, surgical incisions in Sprague-Dawley rats, and acute excisional rat wounds inoculated with Escherichia coli were used. Two concentrations of recombinant human keratinocyte growth factor-2 were compared to a vehicle control and keratinocyte growth factor-1. Keratinocyte growth factor-2 significantly accelerated the rate of epithelialization in the meshed skin graft model and effected a modestly more rapid gain in breaking strength of surgical incisions than keratinocyte growth factor-1 or the vehicle control treatment. Neither keratinocyte growth factors accelerated wound closure by contraction of the excisional wounds. Based on these data, keratinocyte growth factor-2 may be useful in accelerating healing in wounds healing mainly by the process of epithelialization such as venous stasis ulcers, partial thickness burn wounds, and skin graft donor sites. It might also accelerate the gain in incisional wound strength in acute surgical or traumatic wounds.

The efficacy of 5% Sulfamylon solution for the treatment of contaminated explanted human meshed skin grafts.

Large TBSA burns have a deficiency of skin graft donor sites necessitating meshed skin autografts, cultured epithelial autografts or biosynthetic skin substitutes. Because these do not effect immediate complete biological closure of the wound, the burn victim remains at risk for life-threatening infection. Topical antimicrobials can protect colonization of these grafts from becoming invasive sepsis. However, many of these agents are cytotoxic to new partially keratinized epithelial cells. This study using a model of epithelialization kinetics of human meshed skin grafts explanted to athymic 'nude' rats evaluated: (1) the effect of bacterial colonization on the rate of closure of meshed graft interstices; (2) the efficacy of 5% Sulfamylon solution for bacterial control and (3) the effect on interstitial closure rates caused by control of bacterial proliferation. Results showed the rate of interstitial closure was progressive over 7 days in noncontaminated grafts treated with moistened saline dressings. Areas of total closure of a 1:1.5 meshed graft were seen as early as 5 days. When grafts were inoculated with 10(2) or 10(3) Pseudomonas aeruginosa organisms and treated with saline moistened dressings, the resultant bacterial load rose to 10(6) organisms, less than 3% of the interstices closed and grafts were destroyed. With the same organism level of contamination, bacterial levels were eradicated with topical 5% Sulfamylon solution, interstitial closure rates returned to normal and areas of total meshed graft closure were seen by day 4. These data demonstrate the efficacy of 5% Sulfamylon solution on epithelialization kinetics of contaminated meshed skin grafts.