Improve Skin Flap Survival Research Articles

Enhancing Skin Flap Survival with Preoperative Carbon Dioxide Fractional Laser Treatment: A Novel Approach in Reconstructive Surgery

Background: Skin flap necrosis remains a significant challenge in reconstructive surgery, predominantly due to insufficient blood supply. Traditional methods like the surgical delay procedure, while effective, are invasive and associated with considerable patient discomfort and health care costs. This study explores the efficacy of Carbon Dioxide Fractional Laser (CDFL) treatment as a novel, less invasive alternative to enhance skin flap survival. Methods: Twenty-nine adult male Sprague-Dawley rats were divided into 2 groups: a CDFL treatment group (n=14) and a control group (n=15). The CDFL group received laser pretreatment 1 week before flap surgery, whereas the control group underwent flap surgery without pretreatment. Flap survival was assessed 7 days postsurgery using indocyanine green fluorescence angiography. In addition, histological analysis was conducted to evaluate tissue integrity, capillary density, and VEGF expression. Results: The CDFL-treated flaps showed significantly increased survival areas compared with controls (P<0.01). Histological evaluation revealed enhanced capillary dilation and increased VEGF expression in the CDFL group (P<0.05). Although capillary density was higher in the CDFL group, it did not reach statistical significance (P=0.052). Conclusion: CDFL pretreatment significantly improves skin flap survival in rats, suggesting potential as a minimally invasive alternative to traditional surgical delay techniques. This approach could offer substantial benefits in reconstructive surgery, reducing patient morbidity and associated costs. Further studies are warranted to confirm these findings in clinical settings.

Chronic Cinacalcet improves skin flap survival in rats: the suggested role of the nitric oxide pathway.

Cinacalcet is a calcimimetic medicine that has been used to treat secondary hyperparathyroidism and parathyroid cancer. Various studies have proposed the positive role of calcium and its receptor in skin wound healing. Furthermore, Cinacalcet interacts with other skin repair-related mechanisms, including inflammation and nitric oxide pathways. The present study evaluated the effect of Cinacalcet on the random-pattern skin flap survival. Eighty-four Wistar male rats were used. Multiple doses of Cinacalcet (30, 3, 1, 0.3, and 0.05 mg/kg) were used in 3 different routes of administration before the surgery. Histopathological evaluations, quantitative assessment of IL-6, TNF-α, and nitric oxide (NO), and the expression of calcium-sensing receptor (CaSR) and E-cadherin were evaluated in the skin tissue. To assess the role of NO, a NO synthase inhibitor, N-nitro-L-arginine methyl ester hydrochloride (L-NAME), was used, and histopathological effects were investigated. Cinacalcet pretreatment at the IP chronic 1 mg/kg dose significantly increased the skin flap survival rate and enhanced the NO tissue level compared to the control. However, the administration of L-NAME abolished its protective effects. IP Chronic 1 mg/kg of Cinacalcet could also decline the levels of IL-6 and TNF-α and also increase the expression of CaSR and E-cadherin in the flap tissue compared with the control group. Chronic Cinacalcet at 1 mg/kg could improve skin flap survival, probably mediated by the CaSR, NO, and inflammation-related pathways.

Desmopressin enhances random-pattern skin flap survival in rats: Possible role of vasopressin Type-1a and 2 receptors

BackgroundMany drugs have been explored for their role in improving skin flap survival. 1-deamino-8-D-arginine vasopressin (DDAVP or desmopressin) is a synthesized form of anti-diuretic hormone (ADH) and a selective agonist for vasopressin type-2 receptors (V2 receptors). Desmopressin has been shown to improve endothelial function, induce vasodilation, and reduce inflammation. We aimed to evaluate its efficacy in enhancing flap survival and assess the role of vasopressin receptors in this process. Materials and methodsWe randomly assigned six male Wistar rats to each study group. Different doses of desmopressin were injected intraperitoneally to find the most effective amount (8 μg/rat). SR-49059, a selective V1a receptor antagonist, was given at 2μg/rat before providing the most effective dose of desmopressin (8μg/rat). Histopathological assessments, quantitative measurements of interleukin-1β (IL-1β), Tumor necrosis factor-alpha (TNF-α), and Nuclear Factor-κB (NF-κB), optical imaging, and measurement of the expression levels of V2 receptor in the rat skin tissue were performed. ResultsDesmopressin (8μg/rat) significantly reduced the mean percentage of necrotic area compared to the control group (19.35% vs 73.57%). Histopathological evaluations revealed a notable reduction in tissue inflammation, edema, and degeneration following administration of desmopressin (8). The expression of the V2 receptor was increased following desmopressin administration. It also led to a reduction in IL-1β, TNF-α, and NF-κB levels. The protective effect of desmopressin on flap survival was reversed upon giving SR-49059. The optical imaging revealed enhanced blood flow in the desmopressin group compared to the control group. ConclusionsDesmopressin could be repurposed to improve flap survival. V1a and V2 receptors probably mediate this effect.

The Promising Effect of Colchicine on Random-Pattern Skin Flap Survival in Rats: Glutamate Pathway.

Random-pattern skin flap is a conventional procedure in reconstructive surgery, yet partial or complete flap necrosis has remained a major issue. Herein, we investigated the potential effects of colchicine on skin flap survival through the glutamate pathway and N-methyl-D-aspartate (NMDA) receptors. Wistar male rats were injected multiple doses of colchicine intraperitoneally (0.02, 0.05, 0.1, and 0.4mg/kg) before the surgery. MK-801 (a noncompetitive NMDA receptor antagonist) was administered in combination with colchicine to assess the role of glutamate. Histopathological evaluation; quantitative assessment of glutamate, IL-6, and TNF-α; and the expression of NR2A-type NMDA receptors were performed in the skin tissue. Colchicine 0.05mg/kg could significantly promote flap survival compared to the control group (P<0.001), while administration of MK-801 (0.05mg/kg) reversed the effect of colchicine (0.05mg/kg) (P<0.001). Levels of IL-6 and TNF-α decreased, and the expression of NR2A-type NMDA receptors was enhanced in the flap tissue of colchicine 0.05mg/kg group compared to the controls. Also, glutamate level significantly increased after the administration of colchicine 0.05mg/kg compared to the controls (P<0.05). We found that colchicine could improve skin flap survival remarkably in rats that have undergone skin flap surgery through the glutamate pathway and NMDA receptors.

Dynamically Responsive Scaffolds from Microfluidic 3D Printing for Skin Flap Regeneration.

Biological scaffolds hold promising perspectives for random skin flap regeneration, while the practical application is greatly limited by their insufficient vascularization ability and the lack of responsiveness during the dynamical healing process. Herein, a novel MXene‐incorporated hollow fibrous (MX‐HF) scaffold with dynamically responsive channels is presented for promoting vascularization and skin flap regeneration by using a microfluidic‐assisted 3D printing strategy. Benefiting from the photothermal conversion capacity of the MXene nanosheets and temperature‐responsive ability of poly(NIPAM) hydrogels in the MX‐HF scaffolds, they display a near‐infrared (NIR)‐responsive shrinkage/swelling behavior, which facilitates the cell penetration into the scaffold channels from the surrounding environment. Moreover, by incorporating vascular endothelial growth factor (VEGF) into the hydrogel matrix for controllable delivery, the MX‐HF scaffolds can achieve promoted proliferation, migration, and proangiogenic effects of endothelial cells under NIR irradiation. It is further demonstrated in vivo that the NIR‐responsive VEGF@MX‐HF scaffolds can effectively improve skin flap survival by promoting angiogenesis, decreasing inflammation, and attenuating apoptosis in skin flaps. Thus, it is believed that such responsive MX‐HF scaffolds are promising candidates for clinical random skin flap regeneration as well as other diverse tissue engineering applications.

Hydrogen-rich saline reduces tissue injury and improves skin flap survival on a rat hindlimb degloving injury model

Degloving injuries represent a challenge in plastic surgery. The aim of this study is to acknowledge the protective effects of hydrogen-rich saline (HRS) solution on a rat hindlimb degloved skin flap. Twenty-one Sprague-Dawley rats were divided into three groups (control, saline and HRS). Degloving injury model was established, and flaps were sutured back following 5min of ischemia. The control group did not receive any treatment. The saline group received intraperitoneal physiological saline (10 ml/kg) and the HRS group received intraperitoneal HRS solution (10 ml/kg) postoperatively and daily for 5 days after the operation. Skin samples were obtained for histological, immunohistochemical and biochemical evaluations. Inflammation was lower in the HRS compared with saline (p = 0.02) and control (p = 0.004) groups. Edema was lower in the HRS compared with saline (p = 0.02) and control (p = 0.001) groups. Malondialdehyde (MDA) level was lower in the HRS than the control group (p = 0.01). Total antioxidant level was higher in the HRS compared with saline (p = 0.009) and control (p = 0.03) groups. Total oxidant level was lower in the HRS than the control group (p = 0.02). Oxidative stress index was lower in the HRS compared with saline (p = 0.001) and control (p = 0.0001) groups`. Vascular proliferation was higher in the HRS compared with the control group (p = 0.01). Repeated HRS injections after trauma increased the viability of skin flap in rat degloving injury model by decreasing local tissue injury, due to its antioxidant, anti-inflammatory and angiogenic effects.

"Pingpong racket" flap model for evaluating flap survival.

Random skin flap is widely used to repair tissue defects; however, it is often accompanied by ischemia and necrosis of the distal flap due to inferior axial vascularity. Even though different drugs, biomaterials, and stem cell therapies have been developed to improve the survival of random flap, evaluating the promotion of flap survival remains a big challenge. Based on successful clinical practice, we designed a "Pingpong racket" shape flap in the rat. Without the predetected blood vessels procedure, the "pingpong racket" flap provides a preferable option to evaluate the function of drugs and biomaterials in promoting flap survival. "Pingpong racket" dorsal flaps with different pedicle lengths were developed in the rats. The survival area was evaluated by digital photography and computer-assisted analysis. The quantitative survival area was considered a useful indicator for analyzing drugs' applicability in improving skin flap survival. A new model with a pedicle width of 1cm and a flap diameter of 3cm, in which the length of the pedicle could be tuned, was established. No iliolumbar vessels passed through the pedicle. The necrosis ratio ( round ) of the flap was 29.88% in the 2cm long pedicle, 74.69% in the 3cm long pedicle, 95.52% in the 4cm long pedicle, and in the 5cm long pedicle; necrotic area could be found in both the round part and in the pedicle. The new 3cm long pedicle flap is suitable for evaluating the drugs for promoting skin flap survival. Rat dorsal "Pingpong racket" flap can be easily handled, thus avoiding blood vessels' detection. The flap could achieve comparable results to clinical and alleviate the negative influence of the flap's longitudinal contraction. Besides, it is intuitive and aesthetically pleasing.

Ivermectin Increases Random-Pattern Skin Flap Survival in Rats: The Novel Role of GABAergic System

Ivermectin (IVM) was first used as an antiparasitic agent; however, the role of this drug evolved into a broad spectrum. Many mechanisms have been proposed, including interaction with the GABAergic system. Considering the presence of GABA receptor in the skin tissue and its role in ischemia-reperfusion I/R injury, we aimed to evaluate the effect of IVM through GABA receptors on random-pattern skin flap survival. Sixty Wistar male rats were used. Multiple doses of IVM (0.01, 0.05, 0.2, and 0.5mg/kg) were injected intraperitoneally before the surgery. Baclofen (selective GABAB agonist) and bicuculline (selective GABAA antagonist) were administered in combination with IVM to assess the role of the GABAergic system. Histopathological evaluations, immunohistochemical staining, quantitative assessment of IL-1β and TNFα, and the expression of GABAA α1 subunit and GABAB R1 receptors were evaluated in the skin tissue. IVM 0.05mg/kg could significantly increase flap survival compared with the control group (P<0.001). Subeffective dose of baclofen (0.1mg/kg) had synergistic effect with the subeffective dose of IVM (0.01mg/kg) (P<0.001), whereas bicuculline 1mg/kg reversed the effect of IVM (0.05mg/kg) (P<0.001). IVM 0.05mg/kg could also decrease the IL-1β and TNFα levels and increase the expression of GABAA α1 subunit and GABAB R1 receptors in the flap tissue compared with the control group. IVM could improve skin flap survival, probably mediated by the GABAergic pathway. Both GABAA and GABAB receptors are involved in this process. This finding may repurpose the use of old drug, "Ivermectin."

Exenatide improves random-pattern skin flap survival via TFE3 mediated autophagy augment.

Random-pattern skin flaps are widely applied to rebuild and restore soft-tissue damage in reconstructive surgery; however, ischemia and subsequent ischemia-reperfusion injury lead to flap necrosis and are major complications. Exenatide, a glucagon-like peptide-1 analog, exerts therapeutic benefits for diabetic wounds, cardiac injury, and nonalcoholic fatty liver disease. Furthermore, Exenatide is a known activator of autophagy, which is a complex process of subcellular degradation that may enhance the viability of random skin flaps. In this study, we explored whether exenatide can improve skin flap survival. Our results showed that exenatide augments autophagy, increases flap viability, enhances angiogenesis, reduces oxidative stress, and alleviates pyroptosis. Coadministration of exenatide with 3-methyladenine and chloroquine, potent inhibitors of autophagy, reversed the beneficial effects, suggesting that the therapeutic benefits of exenatide for skin flaps are due largely to autophagy activation. Mechanistically, we identified that exenatide enhanced activation and nuclear translocation of TFE3, which leads to autophagy activation. Furthermore, we found that exenatide activates the AMPK-SKP2-CARM1 and AMPK-mTOR signaling pathways, which likely lead to exenatide's effects on activating TFE3. Overall, our findings suggest that exenatide may be a potent therapy to prevent flap necrosis, and we also reveal novel mechanistic insight into exenatide's effect on flap survival.

Dickkopf 2-Expressing Adenovirus Increases the Survival of Random-Pattern Flaps and Promotes Vasculogenesis in a Rat Model.

Dickkopf 2 (DKK2) has important roles in vertebrate development; it inhibits Wnt signaling-related processes, such as axial patterning, limb development, somitogenesis, and eye formation. However, DKK2 also acts as a Wnt signaling agonist. Dickkopf 2, induced during endothelial cell morphogenesis, promotes angiogenesis in cultured human endothelial cells. In this study, we explored the effect of DKK2-expressing adenovirus on random-pattern flaps using a rodent model. A DKK2-expressing (dE1-RGD/DKK2) adenovirus was generated and 20 Sprague-Dawley rats were randomly divided into 2 groups: a DKK2 group and a control group. Each group was intradermally injected with 1 × 10 plaque-forming units of DKK2-expressing adenovirus (DKK2 group) or control virus (control group) 48 hours before and immediately before surgery. Then, random-pattern dorsal cutaneous flaps of 3 × 9 cm were elevated. Flap survival rates and cutaneous blood flow were measured over time, and immunohistochemical staining was performed 10 days after surgery to detect CD31 and vascular endothelial growth factor (VEGF). Immunofluorescence staining confirmed the expression of DKK2 in the DKK2 group. The flap survival rate was higher in the DKK2 group (80.0 ± 4.49%) than in the control group (57.5 ± 4.21%; P < 0.05). Blood flow to the most distal compartment was higher in the DKK2 group than the control group during the early postoperative period. Although vascular density was greater in the DKK2 group, there was no difference in the VEGF concentration between groups. The findings of the present study suggest that the DKK2-expressing adenovirus increases the survival of the random-pattern cutaneous flap independently of VEGF. The administration of the DKK2-expressing adenovirus into elevated skin flaps increased the number of capillaries and blood flow, thereby improving skin flap survival.

Autologous administration of adipose stromal cells improves skin flap survival through neovascularization: An experimental study.

One of the most severe complications in aesthetic and reconstructive surgeries is the partial or total necrosis of a skin flap. In our experimental study, we demonstrated the use of adipose-derived stem cells in the increase of skin flap survival rates. Stem cells were isolated from the fat of Wistar rats and genetically modified to permanently produce a green fluorescent protein (GFP). Two random-pattern skin flaps (2 cm × 8 cm) were elevated on the dorsal area of the spine, and after being separated from the surgical wounds with a thin silicone sheet, they were placed back onto their original location. Then, the autologous GFP-producing cells were injected intradermally into the dorsal area of the rats. At the seventh day, after the implantation of the stem cells, a clinical and immunohistochemical control was performed. The fluorescence microscopy revealed green vascular formations, suggesting that autologous GFP stromal cells were converted into endothelial cells through neovascularization. In the control skin flaps, where no stromal cells were used, no fluorescence was observed. The statistical analysis showed significantly lower necrosis rates in the right-sided flaps (i.e., the flaps where adipose-derived stromal cells were injected) compared with the left-sided ones. Findings from our study demonstrate that adipose-derived stem cells play an important role in the improvement of skin flap survival. Neovascularization is an effective way of achieving it.

Fat Extract Improves Random Pattern Skin Flap Survival in a Rat Model.

Adipose tissue and its derivatives, including adipose-derived stem cells, stromal vascular fraction (SVF), and SVF-gel, have been utilized in the treatment of many ischemic disorders. However, the utilization of these products is limited in clinical applications by concerns related to the presence of cells in these derivatives. This study aimed to isolate a cell-free fat extract (FE) from fat tissue and to evaluate its proangiogenic ability in vitro as well as its protective effects on skin flap survival in vivo. FE was isolated from human fat via a mechanical approach. The concentrations of several growth factors in the FE were determined by enzyme-linked immunosorbent assay. The proangiogenic ability of FE was evaluated utilizing assays of the proliferation, migration, and tube formation in human umbilical vein endothelial cells in vitro. The protective effects of FE on the survival of random pattern skin flaps were investigated by subcutaneous injection into rats. Enzyme-linked immunosorbent assay results revealed that FE contained proangiogenic growth factors that promoted proliferation, migration, and tube formation in human umbilical vein endothelial cells in vitro. In addition, FE reduced skin flap necrosis and increased survival, as demonstrated by macroscopic measurements and blood flow analysis. Histological analysis revealed that FE treatment increased the capillary density. FE is a cell-free, easy-to-prepare, and growth-factor-enriched liquid derived from human adipose tissue that possesses proangiogenic activity and improves skin flap survival by accelerating blood vessel formation. FE may be potentially used for treating ischemic disorders.

Acute Activation of α7-Nicotinic Receptors by Nicotine Improves Rodent Skin Flap Survival Through Nitrergic System.

Recent reports have identified angiogenic, anti-inflammatory, and antioxidant properties of acute treatment with nicotine via activation of nicotinic acetylcholine receptors (nAChRs). In addition, the nitric oxide (NO) pathway is involved in ischemic reperfusion injuries. We investigated the effects of acute pretreatment with nicotine in a rat model of random-pattern skin flap and the potential role of the NO pathway. The Sprague-Dawley rats received increasing doses of (-)-nicotine (0.5, 1, 1.5, 2, and 3 mg/kg) before the procedure. Dorsal skin flaps with caudal pedicles were elevated at the midline, and flap survival was evaluated 7 days after surgery. In addition, animals received an α7-nAChR antagonist, methyllycaconitine, with nicotine. Quantitative reverse transcription polymerase chain reaction was also applied to measure the dermal expression of α7-nAChR. Next, a nonselective NO synthase inhibitor, N-nitro-L-arginine methyl ester hydrochloride; a selective inducible NO synthase inhibitor, aminoguanidine; and an NO precursor, L-arginine, were administered with nicotine. Nicotine at doses of 1, 1.5, and 2 mg/kg significantly increased flap survival, whereas the protective effects of nicotine disappeared at higher doses. Methyllycaconitine completely reversed the protective effects of nicotine and the elevated cutaneous expression of α7-nAChR in nicotine-pretreated rats. In addition, systemic administration of N-nitro-L-arginine methyl ester hydrochloride or aminoguanidine with an effective dose of nicotine caused a significant decrease in flap survival. Conversely, coinjection of a subeffective dose of L-arginine with the subeffective dose of nicotine significantly boosted its protective effects. Acute pretreatment with nicotine by stimulating the expression and activation of cutaneous α7-nAChR improves skin flap survival, which is partially mediated through modulation of the NO pathway.

Combination therapy profoundly improved skin flap survival by modulating KATP channels and nitric oxide

PurposeA potential therapeutic approach on skin flap necrosis is to target parallel pathways involved in necrosis. Azelaic Acid, Minoxidil and Caffeine combination was tried on skin flap survival by their possible interaction with ATP sensitive potassium (KATP) channels and nitric oxide pathway. Material and methodsSprauge-Dawley rats were divided into 8 groups for skin flap surgery. Azelaic acid, minoxidil, caffeine, or their combination were applied topically in different groups. Two additional groups were treated with L-NAME or glibenclamide in addition to the combination therapy. Percentage of flap necrosis was calculated and flap samples were removed to measure tissue malondialdehyde (MDA) and nitric oxide (NO) and expression of inducible nitric oxide synthase (iNOS), Bcl-2 and Bax proteins. ResultsCombination therapy profoundly decreased skin flap necrosis, tissue MDA contents, and expression of the pro-apoptotic protein Bax (p < 0.05 vs. single treatments). These effects were reversed by L-NAME and glibenclamide pre-treatments. Further evaluations showed combination therapy increases flap tissue NO content and iNOS expression (p < 0.05 vs. single treatments). ConclusionBeneficial effect of the combination therapy with azelaic acid, minoxidil and caffeine therapy on rescuing the flap from necrosis by targeting parallel signaling pathways suggested potential applications in clinical practice.

Protective effect of luteolin on skin ischemia-reperfusion injury through an AKT-dependent mechanism.

Cutaneous ischemia-reperfusion (I/R) injury is one of the most crucial problems in flap surgery, which affects the survival of the skin flap and patient prognosis, luteolin, a plant derived flavonoid, has previously been shown to exert a variety of beneficial effects for reducing I/R injury in several organs. The aim of the present study was to evaluate the anti-inflammatory and anti-oxidative stress effects of luteolin on cutaneous I/R injury. The in vitro study were performed using a permanent human immortalized epidermal keratinocyte cell line (HaCaT), cells were cultured in the presence of luteolin and were then treated with hydrogen peroxide, the cell viability, mitochondrial membrane potential and the cell survival/apoptosis related signaling pathway activation were assessed to investigate the cytoprotective effects of luteolin. For in vivo experiments, skin flap I/R injury animal model was established in Sprague-Dawley rats, by measuring the area of flap survival, analyzing the expression of pro-inflammatory cytokine and evaluation of the histological changes in the skin tissue, the protective effects of luteolin on skin I/R injury were investigated. The function of protein kinase B (AKT) and heme oxygenase-1 (HO-1) activation on luteolin mediated I/R injury protection was assessed by administration of phosphoinositide-3-kinase/AKT inhibitor LY294002 and HO-1 inhibitor ZNPP. The results showed that luteolin treatment significantly increased the viability of HaCaT cells upon exposure to hydrogen peroxide, and the administration of luteolin in vivo significantly improved skin flap survival in the I/R injury rat model. The mechanisms underlying these beneficial effects included increased phosphoinositide-3-kinase/protein kinase B activation, improved expression of antioxidant enzyme, and scavenging the cytotoxic effects of reactive oxygen species (ROS). Taken together, the results suggested that luteolin preconditioning yielded significant protection against cutaneous I/R injury by protecting skin keratinocytes from ROS-induced damage.

Oral administration of alanyl-glutamine and glutamine improve random pattern dorsal skin flap survival in rats.

Objective(s):Skin flap necrosis is the most common postoperative side effect in reconstructive surgeries. Glutamine (GLN) has been shown to accelerate wound healing process. The purpose of this study was to evaluate the effects of GLN either in free form or in the dipeptide form along with L- alanyl (Ala-GLN) on random skin flaps survival in rats.Materials and Methods:Dorsal skin flaps with caudal bases (8 ×2 cm) were established in 24 adult male Wistar rats. Then, the animals were randomly assigned into 3 groups (n=8). Control, GLN (0.75 g/kg) and Ala-GLN (0.75 g/kg). All groups administrated orally 24 and 6 hr before flap elevation and continued repeatedly daily until 7 days postoperation. The flap survival rate and vascular density using histological analysis were evaluated. Vascular endothelial growth factor (VEGF) by immunohistochemical method was determined.Results:Seven days after surgery, the mean surviving area in the GLN and Ala-GLN groups were significantly greater than in the untreated control group (P<0.001). Furthermore, in comparison with the control group, the number of blood vessels and VEGF-positive cells in treated groups with GLN and Ala-GLN were significantly higher. However, no significant differences were observed between treated groups with GLN and Ala-GLN.Conclusion:The findings from this study indicate that oral administration of GLN in free form or in the dipeptide (Ala-GLN) could promote neovascularization and improve skin flap survival in rats.

The optimal timing of adipose derived stem cells injection to improve skin flap survival in a rat model

Background Skin flap surgery is a cornerstone in plastic surgery. However, flaps may encounter postoperative partial or complete necrosis. Different modalities have been used to enhance skin flap survival. Adipose-derived stem cells (ASCs) can promote angiogenesis and improve skin flap survival. We aimed to investigate the appropriate timing of ASC administration to get the maximal angiogenic effect and better skin flap survival in rat model.

Fat Extract Improves Random Pattern Skin Flap Survival in a Rat Model

Backgrounds: Adipose tissue, as well as their derivatives, including adipose derived stem cells, stromal vascular fraction (SVF), and SVF-gel, have been used in the treatment of many ischemic disorders but limited by cell-related concerns in clinical application. The aim of this study is to isolate a cell-free fat extract (FE) from fat tissue, and evaluate its proangiogenic ability in vitro as well as its protective effects on skin flap survival in vivo. Methods: FE was isolated from hunam fat via mechanical approach. The levels of various growth factors in the FE were measured by the enzyme-linkedimmunosorbent assay (ELISA). The proangiogenic ability of FE was evaluated on cell proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. The protective effects on survival of random pattern skin flap were investigated in rats by subcutaneous injection of FE. Findings: The ELISA results revealed that the FE contain high levels of proangiogenic growth factors and FE promoted the proliferation, migration and tube formation of HUVECs in vitro. In addition, FE reduced the necrosis of skin flap and enhanced the their survival, which were demonstrated by macroscopic measurement and blood flow analysis. Histological analysis revealed that capillary densities were enhanced by FE treatment. Interpretation: FE is a cell-free, easy-to-prepare and growth factors-enriched liquid derived from human adipose tissue, which possesses proangiogenic activity and improves skin flap survival by accelerating blood vessel formation. It could be potentially used for treating ischemic disorders. Funding: This work was supported by the National Natural Science Foundation of China (81771993), the National Key Research and Development Program of China (2016YFC1101400), and the Natural Science Foundation of Shanghai (16ZR1419800). Declaration of Interest: The authors declare that they have no conflicts of interest. Ethical Approval: The study was approved by the Ethics Committee of Shanghai Jiaotong University School of Medicine, Shanghai, China.

Effect of oxytocin on the survival of random skin flaps.

Random flap transplantation is widely used to repair and rebuild skin soft tissue. However, such flaps exhibit poor survival. Plastic surgeons seek to improve flap survival. We explored whether oxytocin improved skin flap survival. Overlength random skin flaps (9 × 3 cm) were established on backs of 80 healthy male SD rats randomly divided into two groups. One group was injected daily with oxytocin (1 mg/kg; test group) and the other with normal saline (control group). On postoperative day 2, malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured. On postoperative day 7, the flap survival area was measured using transparent graph paper. Microvessel numbers were evaluated histologically by hematoxylin and eosin staining. VEGF expression was assessed immunohistochemically. Angiogenesis was evaluated via lead oxide–gelatin angiography and blood flow via laser Doppler flowmetry. In the test group compared with the control group, the flap survival rate and SOD activity were increased markedly, the MDA level was decreased, and according to hematoxylin and eosin staining, inflammation was significantly attenuated. In addition, the test group exhibited higher levels of VEGF and skin flap angiogenesis. Oxytocin improved flap survival rate by increasing microcirculation and angiogenesis and attenuating ischemia–reperfusion injury.

Ethyl pyruvate improves skin flap survival after ischaemia reperfusion injury.

Background & objectives:Reperfusion after ischaemia is detrimental to the tissues. The oxidative stress created and cytokines released are mostly responsible in this process. In this study, ethyl pyruvate, a known agent for its anti-inflammatory and antioxidant properties, was used to investigate the effects on ischaemia/reperfusion injury on skin island flaps in rats.Methods:Sixty rats were randomly distributed in three groups (non-ischaemic, ischaemic and medication groups). Ethyl pyruvate was administered in the medication group with a dose of 50 mg/kg. After 24 h and one week, the animals were sacrificed, and the flaps were analyzed macroscopically, histopathologically, biochemically (total nitrite, malondialdehyde and myeloperoxidase).Results:Biochemical markers indicating oxidative stress, were found elevated in ischaemic group, whereas medication with ethyl pyruvate significantly reduced these values. There was a significant reduction (P<0.05) in the levels of these markers between ischaemic and medication groups. Ethyl pyruvate improved all the parameters significantly.Interpretation & conclusion:Ethyl pyruvate showed strong scavenger activity against reactive oxygen species. It could be a potential candidate to improve the flap viability in reconstructive microsurgery, especially in free tissue transfers. However, more studies are warranted in experimental models to confirm these findings.