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.
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.
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