Differential Evaluation of Excisional Non-occluded Wound Healing in db/db Mice

Tkalčević, Vanesa Ivetić; Čužić, Snježana; Parnham, Michael J.; Pašalić, Ivanka; Brajša, Karmen

doi:10.1177/0192623308329280

Cited by 44 publications

(35 citation statements)

References 35 publications

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“…The mice were maintained on a 12-h light-dark cycle at room temperature and acclimatized to the environment for at least a week before use in experiments. Skin excision injuries were induced as described previously, with some alterations (21). All researchers wore caps, sterile gloves, gowns, and shoe covers when handling the mice.…”

Section: Methodsmentioning

confidence: 99%

Use of the Antimicrobial Peptide Pardaxin (GE33) To Protect against Methicillin-Resistant Staphylococcus aureus Infection in Mice with Skin Injuries

Huang

Pan

Chan

et al. 2014

Antimicrob Agents Chemother

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Antimicrobial peptides (AMPs) have recently been determined to be potential candidates for treating drug-resistant bacterial infections. Pardaxin (GE33), a marine antimicrobial peptide, has been reported to possess antimicrobial function. In this study, we investigated whether pardaxin promoted healing of contaminated wounds in mice. One square centimeter of outer skin was excised from the ventral region of mice, and a lethal dose of methicillin-resistant Staphylococcus aureus (MRSA) was applied in the presence or absence of methicillin, vancomycin, or pardaxin. While untreated mice and mice treated with methicillin died within 3 days, mice treated with pardaxin survived infection. Pardaxin decreased MRSA bacterial counts in the wounded region and also enhanced wound closure. Reepithelialization and dermal maturation were also faster in mice treated with pardaxin than in mice treated with vancomycin. In addition, pardaxin treatment controlled excess recruitment of monocytes and macrophages and increased the expression of vascular endothelial growth factor (VEGF). In conclusion, these results suggest that pardaxin is capable of enhancing wound healing. Furthermore, this study provides an excellent platform for comparing the antimicrobial activities of peptide and nonpeptide antibiotics.

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Section: Methodsmentioning

confidence: 99%

Use of the Antimicrobial Peptide Pardaxin (GE33) To Protect against Methicillin-Resistant Staphylococcus aureus Infection in Mice with Skin Injuries

Huang

Pan

Chan

et al. 2014

Antimicrob Agents Chemother

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show abstract

“…We accurately determined the early fibroblastic reaction infiltrating the center of the wound in addition to the dense and well-formed granulation tissue at the edges of the wound bed. We believe that this method provides an accurate representation of the fibrovascular reaction associated with the healing process in the whole wound bed, especially in the diabetic mice where infiltration of fibrovascular tissue between the adipocytes is a feature [37].…”

Section: Methodsmentioning

confidence: 99%

PDGF-BB Does Not Accelerate Healing in Diabetic Mice with Splinted Skin Wounds

et al. 2014

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Topical application of platelet-derived growth factor-BB (PDGF-BB) is considered to accelerate tissue repair of impaired chronic wounds. However, the vast literature is plagued with conflicting reports of its efficacy in animal models and this is often influenced by a wide array of experimental variables making it difficult to compare the results across the studies. To mitigate the confounding variables that influence the efficacy of topically applied PDGF-BB, we used a controlled full thickness splinted excisional wound model in db/db mice (type 2 diabetic mouse model) for our investigations. A carefully-defined silicone-splinted wound model, with reduced wound contraction, controlled splint and bandage maintenance, allowing for healing primarily by reepithelialization was employed. Two splinted 8 mm dorsal full thickness wounds were made in db/db mice. Wounds were topically treated once daily with either 3 µg PDGF-BB in 30 µl of 5% PEG-PBS vehicle or an equal volume of vehicle for 10 days. Body weights, wound contraction, wound closure, reepithelialization, collagen content, and wound bed inflammation were evaluated clinically and histopathologically. The bioactivity of PDGF-BB was confirmed by in vitro proliferation assay. PDGF-BB, although bioactive in vitro, failed to accelerate wound healing in vivo in the db/db mice using the splinted wound model. Considering that the predominant mechanism of wound healing in humans is by re-epeithelialization, the most appropriate model for evaluating therapeutics is one that uses splints to prevent excessive wound contraction. Here, we report that PDGF-BB does not promote wound closure by re-epithelialization in a murine splinted wound model. Our results highlight that the effects of cytoactive factors reported in vivo ought to be carefully interpreted with critical consideration of the wound model used.

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“…Color images available online at www.liebertpub.com/tea original wound edge to the area of the wound on day 0. 31,35 On day 14, diabetic wounds had contracted to *40% of their original area (Fig. 2E).…”

Section: Fibronectin Matrix Mimetics Accelerate Wound Closure Of Diabmentioning

confidence: 95%

“…Wound contraction was also determined from corresponding images by tracing the area bordered by the original wound edge, 31,35 which could be clearly distinguished from the leading edge of the new epithelium. Wound contraction is presented as ''Percent Contraction'' and was determined by comparing the area of the wound bordered by the original wound edge to the area of the wound on day 0 as follows:…”

Section: Wound Closurementioning

confidence: 99%