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Background Approximately 200,000 incisional hernias are repaired annually in the United States. The high incidence (11-20%) and recurrence rate (24-54%) for incisional hernias have not changed appreciably in 75 years. Mechanical advances in suture material, incision orientation, and closure technique have failed to eliminate this common surgical complication. A biological approach to acute wound failure may offer a new strategy. Methods. A rodent incisional hernia model was used. Seventy rats underwent 5-cm midline celiotomies and were closed with fine, fast-absorbing sutures to induce intentional acute wound failure. Group 1 received no other treatment. The midline fascia in groups 2 and 3 was injected immediately prior to incision with 100 μl of vehicle alone or vehicle containing 1 μg of transforming growth factor β 2 (TGF-β 2 ). Necropsy was performed on Postoperative Day 28 and the wounds were examined for herniation. Results. Incisional hernias developed in 88% (35/40) and 79% (11/14) of untreated incisions and those treated with vehicle alone. No hernias formed in the TGF-β 2 -treated incisions (0/16, P < 0.05). Standard histology and immunohistochemistry demonstrated enhanced macrophage, lymphocyte, and fibroblast chemotaxis and increased collagen I and III production in TGF-β 2 treated incisions. Conclusions. Treatment of abdominal wall fascial incisions with TGF-β 2 prevented the development of incisional hernias in this rat model. TGF-β 2 stimulated fascial macrophage and fibroblast chemotaxis as well as acute wound collagen production. A biological approach such as this may reduce the incidence of incisional hernia formation in humans.

New treatments for chronic wounds require carefully performed clinical trials with significant endpoints. Total wound closure is the only endpoint currently accepted by the Food and Drug Administration. This study describes a scale that measures ease of wound closure and applies it to a four-arm prospectively randomized, blinded pressure ulcer trial of recombinant human platelet-derived growth factor-BB. Following validation of interrater reliability, 83 evaluable subjects' photographs were given a weekly ease of closure score by four raters blinded to treatment. The change of ease of closure score was correlated with the change of wound area and volume. Each ease of closure score was given a procedural cost. Results showed ease of closure did not directly correlate with either wound area or volume, suggesting that it was measuring additional information. The mean change in ease of closure score was 6 for subjects treated with 100 microg recombinant human platelet-derived growth factor-BB daily; 5 for those treated with 300 microg growth factor daily or 100 microg recombinant human platelet-derived growth factor-BB bid; and 4 for those treated with placebo. The cost savings ranged from $7200 for the group receiving 100 microg recombinant human platelet-derived growth factor-BB daily to $6300 for the controls. Outcomes in all 4 groups were significantly improved from their starting evaluation (p < 0.001). Based on this study, ease of closure is a verifiable endpoint that can be related to cost efficiency and may be a measure of efficacy.

Accurate and clinically practical methods for measuring the progress of acute wound healing is necessary before interventions designed to optimize and even accelerate acute wound healing can be applied. Complete wound closure rates and operative wound closure severity are irrelevant to most acute wounds since most are closed at the time of primary tissue repair and remain closed throughout healing. Analogous to chronic wound closure, the rate of increase of incision tensile strength progressively decreases as time passes and 100% unwounded tissue strength is never achieved making the endpoint definition of "healed" vague. Conceptualizing acute wound healing in terms of its design elements with reintegration into a final outcome lends itself to the description of acute wound healing as a mathematical trajectory. Frequently such an equation is a rate expressing the change in an acute healing parameter, most often tensile strength, over time. Such an approach also normalizes misinterpretations in analysis or errors in theory developed by measuring healing parameters at fixed points in time. Distributions of fractional strength gain times (e.g., 85% normal strength) can be determined using statistical methodology similar that used for failure time of survival analysis. Preclinical studies show that acute wound healing trajectories can be shifted to the left from a "normal" or "impaired" curve to an accelerated or more "ideal" curve. A useful method for measuring acute wound healing outcomes is therefore required before the basic science of acute wound healing is inevitably applied to the problem of acute surgical wounds.

Background Abdominal wall wound failure remains a common surgical problem. The signals that activate normal fibroplastic repair versus regeneration pathways are unknown. Transforming growth factor β levels rise during incisional healing but fall during hepatic regeneration. Changes in the injured host cytokine milieu may therefore differentially effect abdominal wall repair versus hepatic regeneration. Materials and methods. Forty-eight rats were divided into four groups (n = 12). Groups 1-3 underwent sham celiotomy, 70% hepatectomy, or 80% enterectomy with anastamosis. Incisions from Group 4 were treated with either 1 μg of transforming growth factor β 2 (TGF-β 2 ) or vehicle following hepatectomy. Isolated fascial and dermal incisions were harvested and tested for breaking strength on POD 7. Serum (TGF-β 2 ) and hepatocyte growth factor (HGF) levels were measured by ELISA. Results. Recovery of incisional wound breaking strength was delayed following hepatectomy but not enterectomy (P < 0.002). The inhibitory effect was observed in both the fascia and the dermis of the abdominal wall. TGF-β 2 levels were depressed in hepatectomy animals on POD 7, while at the same time HGF levels were elevated. Exogenous TGF-β 2 shifted the healing trajectory of deficient wounds back toward a control pattern. Conclusion. Abdominal wall fascial and dermal healing is delayed during hepatic regeneration. Elevated HGF and depressed TGF-β 2 suggest a host mechanism that prioritizes hepatic parenchymal regeneration over fibroplastic repair (scar). Observations such as these are needed as therapeutic wound healing enters the clinical realm.

Background. The biochemical and cellular pathways resulting in the production of proliferative scar in the thermally injured patient remain incompletely elucidated. A promising area of investigation is the phenomenon of programmed cell death and its modulation. The following study was designed to quantify differential levels of thebcl-2protooncogene and theFascell surface receptor, two apoptosis-modulating proteins, in the peripheral blood mononuclear cell (PBMC) fractions of burn patients with hypertrophic scar versus those considered to have healed normally. The study also encompassed an immunohistochemical examination of fibroblastsin vitro,to identify differential levels of Fas,bcl-2,and interleukin converting enzyme (ICE). Methods. PBMC fractions were isolated from two matched burn patient cohorts of 10 patients each, the experimental group carrying the clinical and histopathologic diagnosis of hypertrophic burn scar. The supernatant from each mitogenically stimulated specimen was halved and subjected to theFas/APO-1 enzyme-linked immunosorbent assay (ELISA) and thebcl-2ELISA. Results for each assay were compared between groups by unpairedttests. Further biopsy specimens of isolated proliferative scar were usedin vitroto analyze the role of these apoptosis-modulating proteins and ICE. This immunoperoxidase technique was analyzed qualitatively. Results. The expression of thebcl-2protein in the PBMC fractions of the burn patients with hypertrophic scar is significantly elevated in comparison to the control cohort (307.72 ± 72.29 u/ml vs 31.55 ± 6.73 u/ml;P= 0.0042). The quantitative levels of theFasreceptor did not differ significantly between the groups, respectively (0.3988 ± 0.179 u/ml vs 0.2899 ± 0.066 u/ml;P= 0.5787). Immunoperoxidase staining of proliferative scar fibroblasts and those from surrounding skin revealed relatively decreased levels of membrane-bound Fas and ICE.bcl-2was not detectable in these specimens. Conclusions. Differential expression of thebcl-2protooncogene and theFascell surface receptor in the PBMC fraction of patients with burn injuries may suggest a disequilibrium in a complex biochemical signaling mechanism mediating programmed cell death. The increased levels ofbcl-2could be responsible for delayed fibroblast apoptosis, resulting in the disruption of normal healing and subsequent hypertrophic scarring. This is confirmed by anin vitroexamination of wound fibroblasts versus those from surrounding uninjured skin. This immunoperoxidase technique reveals a localized relative decrease in Fas and ICE, two apoptosis-inducing proteins, at the level of the fibroblast in the proliferative scar specimen.