Involvement of cannabinoid type 2 (CB2) receptors in the favorable effects of sumatriptan on the random-pattern skin flap survival in rats: a novel potential target

Introduction: Recent investigations have indicated the potential therapeutic role of cannabinoid type 2 (CB2) receptors in various inflammatory-related disorders. However, the role of these receptors has not been studied in skin flap models previously. In this study, we aimed to evaluate the possible involvement of CB2 receptors in the anti-inflammatory effects of sumatriptan and improvement of the random-pattern skin flap survival in rats. Methods: In a controlled experimental study, 36 male Wistar rats were randomly divided into six study groups (n = 6 per group). Two doses of sumatriptan (0.1 and 0.3 mg/kg) were administered intraperitoneally (i.p) 30 minutes before harvesting the flap tissue. In a separate group, SR144528 (a selective CB2 receptor inverse agonist) was injected before the most effective dose of sumatriptan to determine the possible involvement of CB2 receptors in its action. Histopathological examinations, the expression level of CB2 receptors (by western blot analysis), and IL-1 and TNF-α concentrations (ELISA) were explored in the skin flap samples. Results: Sumatriptan 0.3 mg/kg remarkably enhanced the skin flap survival in all macroscopic and microscopic investigations compared to the control group (P <0.001). IL-1 and TNF-α levels were significantly attenuated (P <0.001), and the expression of CB2 receptors in skin cells was amplified in rats treated with sumatriptan 0.3 mg/kg (p <0.05) compared to the control group. However, the administration of SR144528 (2 mg/kg) nullified all the protective effects of sumatriptan (0.3 mg/kg). Conclusion: We discovered that CB2 receptors play a crucial role in the favorable effects of sumatriptan on skin flap survival as a novel mechanism of action. So, targeting these receptors seems to be a dependable method in skin flap surgeries to ensure its survival and prevent tissue necrosis. Further experimental and clinical investigations are needed to ensure the safe clinical application of this method.

Photocrosslinked gelatin hydrogel improves wound healing and skin flap survival by the sustained release of basic fibroblast growth factor

Biomaterials traditionally used for wound healing can act as a temporary barrier to halt bleeding, prevent infection, and enhance regeneration. Hydrogels are among the best candidates for wound healing owing to their moisture retention and drug-releasing properties. Photo-polymerization using visible light irradiation is a promising method for hydrogel preparation since it can easily control spatiotemporal reaction kinetics and rapidly induce a single-step reaction under mild conditions. In this study, photocrosslinked gelatin hydrogels were imparted with properties namely fast wound adherence, strong wet tissue surface adhesion, greater biocompatibility, long-term bFGF release, and importantly, ease of use through the modification and combination of natural bio-macromolecules. The production of a gelatin hydrogel made of natural gelatin (which is superior to chemically modified gelatin), crosslinked by visible light, which is more desirable than UV light irradiation, will enable its prolonged application to uneven wound surfaces. This is due to its flexible shape, along with the administration of cell growth factors, such as bFGF, for tissue regeneration. Further, the sustained release of bFGF enhances wound healing and skin flap survival. The photocrosslinking gelatin hydrogel designed in this study is a potential candidate to enhance wound healing and better skin flap survival.

Positive Effect of Andrographolide Induced Autophagy on Random-Pattern Skin Flaps Survival

Random-pattern skin flap replantation is generally used in the reconstruction of surgical tissues and covering a series of skin flap defects. However, ischemia often occurs at the flap distal parts, which lead to flap necrosis. Previous studies have shown that andrographolide (Andro) protects against ischemic cardiovascular diseases, but little is known about the effect of Andro on flap viability. Thus, our study aimed to building a model of random-pattern skin flap to understand the mechanism of Andro-induced effects on flap survival. In this study, fifty-four mice were randomly categorized into the control, Andro group, and the Andro+3-methyladenine group. The skin flap samples were obtained on postoperative day 7. Subsequently, the tissue samples were underwent a series of evaluations such as changes in the appearance of flap tissue, the intensity of blood flow, and neovascularization density of skin flap. In our study, the results revealed that Andro enhanced the viability of random skin flaps by enhancing angiogenesis, inhibiting apoptosis, and reducing oxidative stress. Furthermore, our results have also demonstrated that the administration of Andro caused an elevation in the autophagy, and these remarkable impact of Andro were reversed by 3-methyladenine (3-MA), the most common autophagy inhibitor. Together, our data proves novel evidence that Andro is a potent modulator of autophagy capable of significantly increasing random-pattern skin flap survival.

Effects of Apigenin Treatment on Random Skin Flap Survival in Rats

Random skin flaps are often used in plastic surgery, but the complications of marginal flap ischemia and necrosis often limit their wider clinical application. Apigenin (Api) is a flavonoid found in various fruits and vegetables. Api has been shown to promote angiogenesis, as well as reduce oxidative stress, membrane damage, and inflammation. In this study, we assessed the effects of Api treatment on random skin flap survival. Dorsal McFarlane skin flaps were transplanted into rats, which were randomly divided into three groups: control (normal saline), low-dose Api (20 mg/kg), and high-dose Api (50 mg/kg). Seven days after the surgery, the activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) were measured. Histological analyses were performed to determine flap survival and tissue edema. H&amp;E staining was performed to assess the histopathological changes in skin flaps, and the levels of microvascular density (MVD) were determined. Laser doppler flowmetry was used to assess microcirculation blood flow. Flap angiography was performed by injection of lead oxide/gelatin. The expression levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interlukin-1β (IL-lβ) were evaluated by immunohistochemistry. Rats in the high-dose Api group exhibited higher average flap survival area, microcirculatory flow, increased SOD activity, and higher VEGF expression levels compared with the other two groups. Furthermore, the levels of MDA and pro-inflammatory cytokines were significantly decreased in rats treated with high-dose Api. Our findings suggest the potential usefulness of Api in preventing skin flap tissue necrosis.

Features of Preoperative Preparation of Patients with Burns and Chronic Ulcers of Various Etiology for Autodermoplasty

The influence of various schemes of preoperative preparation for autodermoplasty on the rates of skin graft survival and the duration of hospitalization in patients with burns and wounds of various etiologies was analyzed. Patients were divided into groups and subgroups depending on the preparation scheme. Group I (22 patients) received negative pressure wound therapy (NPWT) during the preoperative period for 5 days in combination with reamberin — intravenous drip at a rate of 40-60 drops/min, 500 ml, once a day for 5 days. Those patients were divided into subgroups: subgroup 1A (17 people) received complex treatment without antibiotic therapy, subgroup 1B (5 people) received antibiotic therapy. Group II consisted of 30 patients, who received vacuum therapy during the preparatory period. Group II patients were also divided into subgroups: 2A (16 people) received NPWT without antibiotics, 2B (14 people) — vacuum therapy together with antibiotic therapy. Group III (comparison, n=52) included patients who were treated using traditional methods, including antibiotic therapy and topical use of various dressings and ointments. Follow-up morphohistological study of wound biopsies was carried out in order to determine the area of fibroblasts, the area of fibroblast nucleus, and the number of vessels. After skin autografting, skin flap survival rate was determined, taking the time of hospitalization into account. Upon comparison of preoperative preparation schemes used for patients with burns and chronic ulcers of various etiologies with a surface area of 1–5% appropriate for skin autografting, the scheme that included NPWT and reamberin for 5 days proved to be the most effective: an improvement in fibroblastogenesis and blood flow to the wound was noted in this group of patients, which was accompanied by an improvement in the skin flap survival rate up to 90.0±9.9%, which, in turn, reduced the duration of patient’s hospital stay — the average duration of the preoperative period was 2.5 times shorter, postoperative — 1.9 times shorter than in the comparison group (p<0.05). The results obtained make it possible to recommend the use of this scheme in the preoperative preparation for skin autografting for patients with burns and chronic ulcers of various etiologies with the surface area of 1–5%.