Rat Full-thickness Wound Research Articles

081 A New Antiseptic Solution with Potential Applications in Wound Care

Despite the use of antibiotics, antiseptics, and improved sterile techniques, infection remains one of the most frequent complications of wound healing. Infection must be avoided to permit proper wound healing. Systemic and topical antibiotics and antiseptics with broad antimicrobial spectra have been used. Antiseptics have not generally been reported to develop bacterial resistance like antibiotics. Several reports have suggested that antiseptics exhibit significant cytotoxicity toward wound bed cells and may interfere with the normal wound healing process. Thus, for chronic ulcers, the standard of care is debridment and moist dressing with saline. We will describe the properties of a new topical antimicrobial solution, NVC-101. These include its broad-spectrum antimicrobial activities against gram positive, gram negative bacteria, yeast and fungi pathogens, and its lower toxicity as compared to commonly used topical antiseptics. In addition, we will describe the in vivo safety profile of NVC-101 in the rabbit eye and guinea pig sensitization models, as well as 28-day application to full thickness wounds in rats and mini-pigs. Based on these findings, multicenter Phase II clinical trials on infected chronic ulcers are under way.

The biocompatibility of dibutyryl chitin in the context of wound dressings

Dibutyryl chitin (DBC) is a modified chitin carrying butyryl groups at 3 and 6 positions; its peculiarity is that it dissolves promptly in common solvents, while being insoluble in aqueous systems. The high biocompatibility of dibutyryl chitin in the form of films and non-wovens has been demonstrated for human, chick and mouse fibroblasts by the Viability/Cytotoxicity assay, In situ Cell Proliferation assay, Neutral Red Retention assay, Lactate Dehydrogenase Release assay, MTS cytotoxicity assay, and scanning electron microscopy. DBC was hardly degradable by lysozyme, amylase, collagenase, pectinase and cellulase over the observation period of 48 days at room temperature, during which no more than 1.33% by weight of the DBC filaments (0.3 mm diameter) was released to the aqueous medium. DBC non-wovens were incorporated into 5-methylpyrrolidinone chitosan solution and submitted to freeze-drying to produce a reinforced wound dressing material. The latter was tested in vivo in full thickness wounds in rats. The insertion of 4×4 mm pieces did not promote any adverse effect on the healing process, as shown histologically. DBC is therefore suitable for contacting intact and wounded human tissues.

Dermal fibroblasts do not enhance the graft take rate of autologous, cultured keratinocyte suspension on full-thickness wounds in rats.

Dermal fibroblasts are known to play an important role in wound healing. In this study, cultured autologous keratinocyte suspension was applied with fibrin glue to the full-thickness wounds in rats (N = 20). Histological analysis on day 14 showed regenerated epithelium in 10 wounds (50%). Keratinocytes were also premixed with allogeneic dermal fibroblasts in a ratio of 3:1 and 5:1 before application to other full-thickness wounds (N = 20) with fibrin glue. Regeneration of epithelium was observed in 10 (50%) and 9 (45%) wounds respectively. Acute inflammatory reaction and mild to moderate proliferation of fibroblasts in the subepithelial layer of the allogeneic fibroblasts were noted. The addition of dermal fibroblasts to keratinocytes/fibrin glue does not enhance the take rate of the cultured keratinocyte suspension.

The Enhancement in Wound Healing by Transforming Growth Factor-β 1 (TGF-β 1) Depends on the Topical Delivery System

Transforming growth factor-β1 (TGF-β1) has beneficial effects on wound healing. However, the ideal method for its administration to the wound site remains unknown. Our aim was to analyze the release of TGF-β1 from different formulations and to study whether the changes in wound healing by TGF-β1 depend on its topical delivery system. For the studies the TGF-β1 was incorporated into phosphate-buffered saline, into a polyoxamer gel, into DuoDERM hydroactive paste, and into a poly(ethylene oxide) hydrogel. The release of 125I-labeled TGF-β1 from carriers was measured in full-thickness wounds in rats and the healing of the wounds was analyzed by histology and wound area measurements. The TGF-β1 was released from all formulations at a different rate and in an active form as determined by growth inhibition assay. Wound size measurements and the analysis on the amount of cellular influx, fibroplasia, and granulation tissue showed that a single dose (1 μg/wound) of locally administered TGF-β1 significantly ( P < 0.01) enhanced the wound healing. This effect was most prominent with polyoxamer gel formulation, which provided the most sustained release of TGF-β1. Our finding that the enhancement in wound healing by TGF-β1 was significantly dependent on the carrier used for its topical delivery to the wound site is novel and shows the importance of using adequate delivery systems when growth factors are used to enhance wound repair.

Sucralfate induces proliferation of dermal fibroblasts and keratinocytes in culture and granulation tissue formation in full-thickness skin wounds

Sucralfate is used to induce healing of gastrointestinal tract ulcers. We evaluated its potential utility in the healing of skin wounds. Initial experiments examined the effects of the sucralfate on proliferation of cultured dermal fibroblasts and keratinocytes. Sucralfate induced proliferation in quiescent cultures of both cell types. Additionally, sucralfate enhanced prostaglandin E2 synthesis in basal keratinocytes and in interleukin-1-stimulated keratinocytes and dermal fibroblasts. Basal interleukin-1 and 6 release were not affected by sucralfate, but the agent enhanced interleukin-1-stimulated interleukin-6 release from fibroblasts. When applied daily to full-thickness wounds in rats, sucralfate increased the thickness of granulation tissue when assessed at day 12.

Fibronectin, Wound Contraction, and Epithelialization

<h3>To the Editor.—</h3> In the February issue of theArchives, Cheng et al,¹describe the effectiveness of topically applied fibronectin (FN) in the healing of full-thickness wounds in rats. By measuring the area (in square millimeters) of wounds on the backs of rats, they concluded that FN suspended in Orabase significantly accelerated wound healing. We feel that several aspects of their evaluation require further consideration. The first point relates to the role of wound contraction in the healing of the full-thickness wound in their rat model. Cheng et al conclude that the accelerated wound healing observed was due to accelerated epithelialization rather than accelerated contraction. This conclusion rests on the premise that contraction is not an important element for the healing of circular wounds. They do note the importance of contraction in healing irregular or rectangular wounds and, as stated in the "Standard Lesions" section of their article, an