KGF Phage Model Peptide Accelerates Cutaneous Wound Healing in a Diabetic Rat Model

Abstract Background Collagen is the most abundant structural protein in the mammalian connective tissue and represents approximately 30% of animal protein. The current study evaluated the potential capacity of collagen extract derived from Nile tilapia skin in improving the cutaneous wound healing in rats and investigated the underlying possible mechanisms. A rat model was used, and the experimental design included a control group (CG) and the tilapia collagen treated group (TCG). Full-thickness wounds were conducted on the back of all the rats under general anesthesia, then the tilapia collagen extract was applied topically on the wound area of TCG. Wound areas of the two experimental groups were measured on days 0, 3, 6, 9, 12, and 15 post-wounding. The stages of the wound granulation tissues were detected by histopathologic examination and the expression of vascular endothelial growth factor (VEGF), and transforming growth factor (TGF-ß1) were investigated using immunohistochemistry. Moreover, relative gene expression analysis of transforming growth factor-beta (TGF-ß1), basic fibroblast growth factor (bFGF), and alpha-smooth muscle actin (α-SMA) were quantified by real-time qPCR. Results The histopathological assessment showed noticeable signs of skin healing in TCG compared to CG. Immunohistochemistry results revealed remarkable enhancement in the expression levels of VEGF and TGF-β1 in TCG. Furthermore, TCG exhibited marked upregulation in the VEGF, bFGF, and α-SMA genes expression. These findings suggested that the topical application of Nile tilapia collagen extract can promote the cutaneous wound healing process in rats, which could be attributed to its stimulating effect on recruiting and activating macrophages to produce chemotactic growth factors, fibroblast proliferation, and angiogenesis. Conclusions The collagen extract could, therefore, be a potential biomaterial for cutaneous wound healing therapeutics.

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Composite sponges from sheep decellularized small intestinal submucosa for treatment of diabetic wounds

Journal of Biomaterials Applications ◽

10.1177/0885328220963897 ◽

2020 ◽

pp. 088532822096389

Author(s):

Gamze Kara Magden ◽

Cigdem Vural ◽

Busra Yaprak Bayrak ◽

Candan Yilmaz Ozdogan ◽

Halime Kenar

Keyword(s):

Wound Healing ◽

Hyaluronic Acid ◽

Rat Model ◽

Small Intestinal Submucosa ◽

Diabetic Rat ◽

Control Group ◽

Significant Difference ◽

Small Intestinal ◽

Intestinal Submucosa ◽

Diabetic Rat Model

Despite the fast development of technology in the world, diabetic foot wounds cause deaths and massive economical losses. Diabetes comes first among the reasons of non traumatic foot amputations. To reduce the healing time of these fast progressing wounds, effective wound dressings are in high demand. In our study, sheep small intestinal submucosa (SIS) based biocompatible sponges were prepared after SIS decellularization and their wound healing potential was investigated on full thickness skin defects in a diabetic rat model. The decellularized SIS membranes had no cytotoxic effects on human fibroblasts and supported capillary formation by HUVECs in a fibroblast-HUVEC co-culture. Glutaraldehyde crosslinked sponges of three different compositions were prepared to test in a diabetic rat model: gelatin (GS), gelatin: hyaluronic acid (GS:HA) and gelatin: hyaluronic acid: SIS (GS:HA:SIS). The GS:HA:SIS sponges underwent a 24.8 ± 5.4% weight loss in a 7-day in vitro erosion test. All sponges had a similar Young’s modulus under compression but GS:HA:SIS had the highest (5.00 ± 0.04 kPa). Statistical analyses of histopathological results of a 12-day in vivo experiment revealed no significant difference among the control, GS, GS:HA, and GS:HA:SIS transplanted groups in terms of granulation tissue thickness, collagen deposition, capillary vessel formation, and foreign body reaction (P > 0.05). On the other hand, in the GS:HA:SIS transplanted group 80% of the animals had a complete epidermal regeneration and this was significantly different than the control group (30%, P < 0.05). Preclinical studies revealed that the ECM of sheep small intestinal submucosa can be used as an effective biomaterial in diabetic wound healing.

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Comparison of Dietary Oils with Different Polyunsaturated Fatty Acid n-3 and n-6 Content in the Rat Model of Cutaneous Wound Healing

International Journal of Molecular Sciences ◽

10.3390/ijms21217911 ◽

2020 ◽

Vol 21 (21) ◽

pp. 7911

Author(s):

Tomas Komprda ◽

Zbysek Sladek ◽

Zuzana Sevcikova ◽

Veronika Svehlova ◽

Jan Wijacki ◽

...

Keyword(s):

Wound Healing ◽

Fish Oil ◽

Rat Model ◽

Tissue Response ◽

Safflower Oil ◽

Cutaneous Wound Healing ◽

Feed Mixture ◽

Cutaneous Wound ◽

Dietary Oils ◽

Collagen Iii

Dietary supplementation with polyunsaturated fatty acids (PUFA) n-3 can affect cutaneous wound healing; however, recent findings demonstrate the variable extent of their influence on the quality of healing. Here, we compare the effect of several dietary oils, containing different levels of PUFA n-3 and PUFA n-6, on wound healing in the rat model. Rats were fed the feed mixture with 8% palm oil (P), safflower oil (S), fish oil (F) or Schizochytrium microalga extract (Sch) and compared to the animals fed by control feed mixture (C). Dorsal full-thickness cutaneous excisions were performed after 52 days of feeding and skin was left to heal for an additional 12 days. Histopathological analysis of skin wounds was performed, including immune cells immunolabeling and the determination of hydroxyproline amount as well as gene expression analyses of molecules contributing to different steps of the healing. Matrix-assisted-laser-desorption-ionization mass-spectrometry-imaging (MALDI-MSI) was used to determine the amount of collagen α-1(III) chain fragment in healing samples. Treatment by Schizochytrium extract resulted in decrease in the total wound area, in contrast to the safflower oil group where the size of the wound was larger when comparing to control animals. Diet with Schizochytrium extract and safflower oils displayed a tendency to increase the number of new vessels. The number of MPO-positive cells was diminished following any of oil treatment in comparison to the control, but their highest amount was found in animals with a fish oil diet. On the other hand, the number of CD68-positive macrophages was increased, with the most significant enhancement in the fish oil and safflower oil group. Hydroxyproline concentration was the highest in the safflower oil group but it was also enhanced in all other analyzed treatments in comparison to the control. MALDI-MSI signal intensity of a collagen III fragment decreased in the sequence C > S > Sch > P > F treatment. In conclusion, we observed differences in tissue response during healing between dietary oils, with the activation of inflammation observed following the treatment with oil containing high eicosapentaenoic acid (EPA) level (fish oil) and enhanced healing features were induced by the diet with high content of docosahexaenoic acid (DHA, Schizochytrium extract).

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