A series of in situ gelable hydrogels were prepared from oxidized dextran (Odex) and N-carboxyethyl chitosan (CEC) without any extraneous crosslinking agent. The gelation readily took place at physiological pH and body temperature. The gelation process was monitored rheologically, and the effect of the oxidation degree of dextran on the gelation process was investigated. The higher the oxidation degree of Odex, the faster the gelation. A highly porous hydrogel structure was revealed under scanning electron microscopy (SEM). Swelling and degradation of the Odex/CEC hydrogels in PBS showed that both swelling and degradation were related to the crosslinking density of the hydrogels. In particular, the hydrogels underwent fast mass loss in the first 2 weeks, followed by a more moderate degradation. The results of long-term cell viability tests revealed that the hydrogels were non-cytotoxic. Mouse fibroblasts were encapsulated in the hydrogels and cell viability was at least 95% within 3 days following encapsulation. Furthermore, cells entrapped inside the hydrogel assumed round shape initially but they gradually adapted to the new environment and spread out to assume more spiny shapes. Additionally, the results from applying the Odex/CEC system to mice full-thickness transcutaneous wound models suggested that it was capable of enhancing wound healing.

Deep burns are associated with the formation of an eschar, which delays healing and increases the risk of infection. Surgical debridement of the eschar is, at present, the fastest means to achieve an eschar-free bed, but the process can not differentiate between the viable tissue and the eschar and follow the minute irregularities of the interface between the two. We evaluated the efficacy and selectivity of a novel enzymatic bromelain-based debriding agent, Debrase Gel Dressing (Debrase), in a porcine comb burn model. We hypothesized that Debrase would result in rapid debridement of the eschar without adverse effects on the surrounding uninjured skin. This is a prospective, controlled, animal experiment. Five domestic pigs (20-25 kg) were used in this study. Sixteen burns were created on each animal's dorsum using a brass comb with four rectangular prongs preheated in boiling water and applied for 30 seconds, resulting in four rectangular 10 x 20 mm full-thickness burns and separated by three 5 x 20 mm unburned interspaces representing the zone of stasis. The burned keratin layer (blisters) was removed, and the burns were treated with a single, topical, Debrase or control vehicle application for 4 hours. The Debrase/control was then wiped off using a metal forceps handle, and the burns were treated with a topical silver sulfadiazine (SSD). The wounds were observed, and full-thickness biopsies were obtained at 4 and 48 hours for evidence of dermal thickness, vascular thrombosis, and burn depth, both within the comb burns and the unburned interspaces in between them. Chi-square and t tests are used for data analysis. A single 4-hour topical application of Debrase resulted in rapid and complete eschar dissolution of all the burns in which the keratin layer was removed. The remaining dermis was thinner (1.1 +/- 0.7 mm) than in the control burns (2.1 +/- 0.3 mm; difference 0.9 mm [95% confidence interval: 0.3-1.4]) and was viable with no injury to the normal surrounding skin or to the unburned interspaces between the burns, which represents the zone of stasis. In control burns, the entire thickness of the dermis was necrotic. At 48 hours, Debrase-treated areas were found partially desiccated under SSD treatment. The unburned interspaces demonstrated partial-thickness necrosis in two third and full-thickness necrosis in one third of wounds. In contrast, full-thickness necrosis was noted in all control interspaces (P = .05). In a porcine comb burn model, a single, 4-hour topical application of Debrase resulted in rapid removal of the necrotic layer of the dermis with preservation of unburned tissues. At 48 hours, SSD treatment resulted in superficial tissue damage and partial preservation of the unburned interspaces.

No abstract

Pretreatment of rats with oral curcumin followed by once-daily oral treatment for three days reduced the percentage of unburned skin interspaces that progressed to full necrosis.

Scar formation after thermal injury is common and results in significant aesthetic and functional impairment. Transforming growth factor beta (TGF-beta) plays a significant role in scar formation. We tested the hypothesis that a novel TGF-beta peptantagonist would reduce scar formation and wound contraction in partial thickness burns by using a randomized controlled experiment. The subjects include two domestic pigs (20-25 kg). Forty burns were created on the animal's dorsum using an aluminum bar preheated to 80 degrees C and applied for 20 seconds resulting in a partial thickness thermal burn extending half way down the dermis. Burns were treated every other day for 1 week, then twice weekly for 3 weeks with a topical TGF-beta antagonist or its vehicle. Full thickness biopsies were obtained from all burns at 7, 10, and 14 days after injury. The wounds were completely excised after 28 days for histological assessment. Wound sections were stained with H&&E and evaluated by a dermatopathologist masked to treatment assignment for reepithelialization and depth of scar formation. We also determined the number of wounds at 28 days that healed with contracted, hour-glass shaped scars. Data were compared with chi and t-tests. Twenty burns were treated with TGF-beta antagonist and 20 with control vehicle. TGF-beta antagonist increased the percentage of completely reepithelialized wounds at 14 days (90 vs 45%, P = .002) and reduced the percentage of contracted wounds (35 vs 65%, P = .02) and full thickness scars (10 vs 60%, P = .002) at 28 days. Treatment of partial thickness porcine burns with the TGF-beta antagonist speeds reepithelialization and reduces scar formation and wound contraction in partial thickness porcine burns.

2004) Comparison of woundbursting strengths and surface characteristics of FDA-approved tissue adhesives for skin closure , Abstract-We compared the wound-bursting strength (WBS), mode of adhesive failure and surface characteristicsof two FDA-approved tissue adhesives for skin closure in an incisional rat model using a randomized, controlled, blind animal experiment. Standardized 2-cm full-thickness incisions were made in duplicate on both sides of 15 rats and closed with Indermil, or High Viscosity Dermabond (HVD) following manufacturers' instructions. WBS was measured 5 min later with a validated commercial instrument. Wound sections were also observed under light and scanning electron microscopies. Indermil was signi cantly weaker than HVD (mean difference, 143 mmHg; 95% CI, 42-229 mmHg, P D 0:002). The mode of failure for Indermil was primarily cohesive in the adhesive and the primary failure mode for the HVD was interfacial (Â 2 , P < 0:01). Microscopic observations demonstrated that application of HVD resulted in a thick, uniform and smooth surface while Indermil resulted in a thin, irregular, cracked surface. We conclude that HVD is stronger, thicker and more uniform than Indermil.

Burns induce the activation of an inflammatory cascade that generates reactive oxygen radicals and lipid peroxidation leading to burn wound progression and extension. Peroxisome proliferation-activated receptor-gamma is a nuclear hormone receptor that is activated by transcription factors and plays an important role in the regulation of cellular proliferation and inflammation. We hypothesized that treatment of burns with rosiglitazone, a peroxisome proliferation-activated receptor-gamma ligand, would reduce burn wound progression. This is a randomized controlled study of 20 Sprague-Dawley rats. Two burns were created on each animal's dorsum using a brass comb with four rectangular prongs preheated in boiling water and applied for 30 seconds resulting in four rectangular 10 x 20 mm full thickness burns separated by three 5 x 20 mm unburned interspaces (zone of ischemia). Animals were randomized to rosiglitazone 4 mg/kg or vehicle by oral gavage 30 minutes after injury and at 24 and 48 hours after injury. Wounds were observed at 1, 2, 3, and 4 days after injury for visual evidence of necrosis in the unburned interspaces. Full thickness biopsies from the interspaces were evaluated with hematoxylin and eosin staining 7 days after injury for evidence of necrosis. The percentage of interspaces that progressed to necrosis was compared with chi tests. Forty comb burns with 120 unburned interspaces were evenly distributed between rosiglitazone and vehicle. The number of interspaces that progressed to full thickness necrosis at 1, 2, 3, 4, and 7 days after injury in the rosiglitazone and vehicle groups were 9/60 (15%) versus 13/60 (21%) (P = .48), 16/60 (27%) versus 15/60 (20%) (P = 1.00), 24/60 (40%) versus 46/60 (77%) (P = .001), 35/60 (58%) versus 53/60 (88%) (P = .001), and 43/60 (72%) versus 54/60 (90%) (P = .02), respectively. Treatment with oral rosiglitazone reduces the percentage of unburned skin interspaces that progress to full necrosis in a rat comb burn model.

Pretreatment of rats with oral curcumin followed by once-daily oral treatment for three days reduced the percentage of unburned skin interspaces that progressed to full necrosis.