Skin Flap Survival Research Articles

Camera-based assessment of cutaneous perfusion strength in a clinical setting

Objective. After skin flap transplants, perfusion strength monitoring is essential for the early detection of tissue perfusion disorders and thus to ensure the survival of skin flaps. Camera-based photoplethysmography (cbPPG) is a non-contact measurement method, using video cameras and ambient light, which provides spatially resolved information about tissue perfusion. It has not been researched yet whether the measurement depth of cbPPG, which is limited by the penetration depth of ambient light, is sufficient to reach pulsatile vessels and thus to measure the perfusion strength in regions that are relevant for skin flap transplants. Approach. We applied constant negative pressure (compared to ambient pressure) to the anterior thighs of 40 healthy subjects. Seven measurements (two before and five up to 90 min after the intervention) were acquired using an RGB video camera and photospectrometry simultaneously. We investigated the performance of different algorithmic approaches for perfusion strength assessment, including the signal-to-noise ratio (SNR), its logarithmic components logS and logN, amplitude maps, and the amplitude height of alternating and direct signal components. Main results. We found strong correlations of up to r = 0.694 (p < 0.001) between photospectrometric measurements and all cbPPG parameters except SNR when using the green color channel. The transfer of cbPPG signals to POS, CHROM, and O3C did not lead to systematic improvements. However, for direct signal components, the transformation to O3C led to correlations of up to r = 0.744 (p < 0.001) with photospectrometric measurements. Significance. Our results indicate that a camera-based perfusion strength assessment in tissue with deep-seated pulsatile vessels is possible.

Standardized Skin Flap Warming Effectively Improves Flap Survival without Obstructing Temperature Monitoring after DIEP.

Objective:This study aimed to determine whether skin flap warming after an operation interferes with temperature monitoring. The postoperative nursing workflow of subabdominal deep inferior epigastric artery perforator (DIEP) flap breast reconstruction was optimized.Methods:A retrospective analysis involving 69 patients who received one-stage breast reconstruction at the Huashan Hospital from July 2017 to December 2019 was performed. The postoperative physical care of patients, including flap temperature monitoring and flap warming, was reviewed.Results:All patients had successful operations. After surgery, all flaps were warmed following the standard protocol. Abnormal temperature and compromised circulation of flaps were observed in three of the patients. These patients received re-exploration surgery and all three flaps survived. A postoperative follow-up shows a high level of patient satisfaction in most cases.Conclusions:The appropriate warming of transplanted flaps did not interfere with temperature monitoring. This helped determine whether there was compromised circulation, leading to increased skin flap survival and improved patient satisfaction.

Diallyl Trisulfide Enhances the Survival of Multiterritory Perforator Skin Flaps.

The multiterritory perforator flap is one of the widest flap patterns used to repair tissue defects. However, flap necrosis of the distal part is still a challenging issue for plastic surgeons. Diallyl trisulfide (DATS) is an efficient ingredient extracted from garlic, exerting many important effects on different diseases. Our experiment aims to reveal whether DATS has a beneficial effect on the survival of perforator flaps and to explore its mechanism of action. The results showed that DATS enhanced angiogenesis and autophagy and reduced cell apoptosis and oxidative stress, thereby improving the survival rate of skin flaps. After co-administration with autophagy inhibitor 3-methyladenine (3MA), perforator flap survival was further improved. Mechanistically, we showed that PI3K/Akt and AMPK-HIF-1α signaling pathways in flap were activated under DATS treatment. All in all, DATS promoted the survival of multiterritory perforator flaps via the synergistic regulation of PI3K/Akt and AMPK-HIF-1α signaling pathways, and inhibition of DATS-induced autophagy further improves flap survival.

Effect of paeoniflorin on distal survival of random flaps

BackgroundDistal ischemic necrosisis a common complication of orthopedic random skin flaps surgery. Paeoniflorin, a natural compound extracted from Paeonia lactiflora, can enhances angiogenesis and alleviates excessive inflammatory response. We investigated the changes of ischemic extra-long flaps with paeoniflorin and its possible mechanism. MethodsWe raised dorsal McFarlane flaps in 54 Sprague-Dawley rats. We designed three groups of rats: high-paeoniflorin group (HP, 50 mg/kg/d), low-paeoniflorin group (LP, 20 mg/kg/d), and control group. The flap survival rate was calculated, seven days after flap construction.Blood perfusion was detected by laser Doppler flow imaging, and angiogenesis wasdetected by Lead oxide/gelatin angiography.Oxidative stress levels of flaps were determined by detecting superoxide dismutase (SOD) and malondialdehyde (MDA). The histopathological status of flap was evaluated by hematoxylin and eosin (H&E) staining.Immunohistochemistry was used to determine the expression of high mobility group protein B1 (HMGB1), nuclear factor-kappa B (NF-κB), Toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β, IL-18, vascular endothelial growth factor (VEGF), cysteine protease-1 (caspase-1) and NLPR3. ResultsThe flap survival rates and SOD activity in the experimental groups were significantly higher, while MDA activity was lower. Experimental groups showed significantly improved microcirculatory blood flow to the flap and increased angiogenesis. Immunohistochemistry revealed that paeoniflorin was associated with significantly increased VEGF expression, and decreased level of HMGB1, TLR4, TNF-α, NF-κB, IL-6, IL-1β, caspase-1, NLPR3, and IL-18. ConclusionsPaeoniflorin effectively enhanced the survival of rat random skin flaps by promoting vascular hyperplasia, inhibiting pyroptosis, and down-regulating inflammation.

Rivastigmine Regulates the HIF-1α/VEGF Signaling Pathway to Induce Angiogenesis and Improves the Survival of Random Flaps in Rats.

Random skin flaps are frequently used to repair skin damage. However, the ischemic and hypoxic necrosis limits their wider application. Rivastigmine, a carbamate cholinesterase inhibitor (ChEI), has also been shown to reduce ischemia–reperfusion injury (IRI) and inflammation. This study was performed to examine the effect of rivastigmine on flap survival. Sixty male Sprague–Dawley rats with a modified McFarland flap were randomly divided into three groups: control group, 1 ml of solvent (10% DMSO + 90% corn oil); low-dose rivastigmine group (Riv-L), 1.0 mg/kg; and high-dose rivastigmine group (Riv-H), 2.0 mg/kg. All rats were treated once a day. On day 7, the skin flap survival area was measured. After staining with hematoxylin and eosin (H&E), the pathological changes and microvessel density (MVD) were examined. The expression of inflammatory factors IL-1β and IL-18, CD34, hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial growth factor (VEGF) was examined by immunohistochemical staining. The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were examined to determine the degree of oxidative stress. Lead oxide/gelatin angiography showed neovascularization and laser Doppler blood flowmetry showed the blood filling volume. Rivastigmine significantly increased the flap survival area and improved neovascularization. CD34, VEGF, and HIF-1α expression were increased, These changes were more pronounced in the Riv-H group. Treatment with rivastigmine reduced the level of MDA, improved SOD activity, and reduced expression of IL-1β and IL-18. Our results indicate that Rivastigmine can increase angiogenesis and significantly improve flap survival.

Sub-Flap Use of Nano-Selenium Oxide Solution Enhances Skin Flap Viability in Rats: Study the Novel Role of mTOR and p-mTOR Expression.

Nano-selenium oxide (NSeO) particles are highly noticeable due to their tissue-protective and antioxidant properties. For this purpose, the effect of NSeO was evaluated on skin flap survival and flap oxidative stress markersin rats. Also, another effect of NSeO was investigated on the expression of mTOR and p-mTOR. Fifty rats were divided into five groups of ten. Skin flap size was 3×8 cm in all groups. Groups were: (1) Sham, (2) Flap Surgery group, (3) Flap Surgery + NSeO, (4) Flap Surgery + Rapamycin (mTOR inhibitor), (5) Flap Surgery + Rapamycin + NSeO. The flap necrosis rate was computed using the paper pattern method on day seven after surgery. After day seven, flap tissues were collected for histological evaluations. Then, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured. Furthermore, the expression levels of mTOR and p-mTOR were measured using the Western blot method. Treatment with NSeO significantly reduced necrosis (P&lt;0.05). It also resulted in a decrease in MDA level (P&lt;0.05). Histologically, NSeO reduced inflammation and increased positive signs of tissue healing (epithelialization, neovascularization, fibroblast migration, and granulation tissue). NSeO increased SOD activity significantly (P&lt;0.05), whereas, using rapamycin reversed these effects. Also, in all groups, mTOR changes were not significant. Additionally, p-mTOR expression was significantly reduced in groups that rapamycin was injected. NSeO can reduce flap necrosis and enhance tissue healingin rats. So, it can potentially be used clinically to promote tissue repair significantly, and its effects are independent of the mTOR pathway. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The potential effect of intradermal Botulinum Toxin Type-A (BTA) injection to increase extended random skin flap survival

Background: Extended random skin flap failure often occurs due to insufficient vascularization. Several attempts have been tried to increase the viability of the flap, but none of these attempts have achieved maximal success. Previous research has shown that Botulinum toxin type A (BTA) increases the viability of cutaneous flaps by inhibiting muscle contraction along with increasing vasodilation and angiogenesis. This study examines the effect of intradermal BTA injection on extended random skin flaps viability.Methods: In thirty-six Wistar rats, a rectangular random cutaneous flap (6 cm × 1.5 cm) was made on each dorsal rat area and then elevated the flap. The treatment group was intradermally injected evenly with BTA 8 IU and saline solution for the control group. Each rat flap viability was observed after five days. Primary outcome measures are survival flap area using Visitrak, microscopic assessment of the number and diameter of capillaries and Vascular Endothelial Growth Factor (VEGF) expression was analyzed using immunohistochemistry semi-quantitative scoring system. Data were analyzed using SPSS version 21 for Windows.Results: The treatment group has better results in all observed parameters than the control group. However, Only the VEGF expression of proximal edge showed a statistically significant increase in the group treated with BTA injection (p=0.004).Conclusion: This study showed that the BTA treatment has a positive effect on random skin flap survival and the reduction of distal necrosis in rats, so it has been proven that BTA has the potential to increase flap survival rates in small animal models. Further studies are needed to determine whether BTA treatment can produce similar findings in humans.

Involvement of Cannabinoid Type 2 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 to date. In this study, we aimed to evaluate the possible involvement of CB2 receptors in the anti-inflammatory effects of sumatriptan, improving the random-pattern skin flap survival in rats. Methods: In a controlled experimental study, 36 male Wistar rats were randomly divided into 6 study groups (n = 6 per group). Two doses of sumatriptan (0.1 and 0.3 mg/kg) were administered intraperitoneally 30 min 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 (Western blot analysis), and IL-1β and TNF-α concentrations (ELISA) were explored in the skin flap sampled tissues. 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-1β 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.

Cyclic helix B peptide promotes random-pattern skin flap survival via TFE3-mediated enhancement of autophagy and reduction of ROS levels.

Necrosis of random-pattern skin flaps limits their clinical application. Helix B surface peptide (HBSP) protects tissues from ischaemia-reperfusion injury but its short plasma half-life limits its applications. Here, we have synthesized cyclic helix B peptide (CHBP) and investigated its role in flap survival and the underlying mechanisms. Flap viability was evaluated by survival area analysis, laser Doppler blood flow and histological analysis. RNA sequencing was used to identify mechanisms underlying the effects of CHBP. Levels of autophagy, oxidative stress, pyroptosis, necroptosis and molecules related to the AMP-activated protein kinase (AMPK)-TRPML1-calcineurin signalling pathway were assayed with Western blotting, RT-qPCR, immunohistochemistry and immunofluorescence. The results indicated that CHBP promoted the survival of random-pattern skin flaps. The results of RNA sequencing analysis indicated that autophagy, oxidative stress, pyroptosis and necroptosis were involved in the ability of CHBP to promote skin flap survival. Restoration of autophagy flux and enhanced resistance to oxidative stress contributed to inhibition of pyroptosis and necroptosis. Increased autophagy and inhibition of oxidative stress in the ischaemic flaps were regulated by transcription factor E3 (TFE3). A decrease in the levels of TFE3 caused a reduction in autophagy flux and accumulation of ROS and eliminated the protective effect of CHBP. Moreover, CHBP regulated the activity of TFE3 via the AMPK-TRPML1-calcineurin signalling pathway. CHBP promotes skin flap survival by up-regulating autophagy and inhibiting oxidative stress in the ischaemic flap and may have potential clinical applications.

Inhibition of PLA2G4E/cPLA2 promotes survival of random skin flaps by alleviating Lysosomal membrane permeabilization-Induced necroptosis

ABSTRACT Necrosis that appears at the ischemic distal end of random-pattern skin flaps increases the pain and economic burden of patients. Necroptosis is thought to contribute to flap necrosis. Lysosomal membrane permeabilization (LMP) plays an indispensable role in the regulation of necroptosis. Nonetheless, the mechanisms by which lysosomal membranes become leaky and the relationship between necroptosis and lysosomes are still unclear in ischemic flaps. Based on Western blotting, immunofluorescence, enzyme-linked immunosorbent assay, and liquid chromatography-mass spectrometry (LC-MS) analysis results, we found that LMP was presented in the ischemic distal portion of random-pattern skin flaps, which leads to disruption of lysosomal function and macroautophagic/autophagic flux, increased necroptosis, and aggravated necrosis of the ischemic flaps. Moreover, bioinformatics analysis of the LC-MS results enabled us to focus on the role of PLA2G4E/cPLA2 (phospholipase A2, group IVE) in LMP of the ischemic flaps. In vivo inhibition of PLA2G4E with an adeno-associated virus vector attenuated LMP and necroptosis, and promoted flap survival. In addition, microRNA-seq helped us determine that Mir504-5p was differentially expressed in ischemic flaps. A string of in vitro and in vivo tests was employed to verify the inhibitory effect of Mir504-5p on PLA2G4E, LMP and necroptosis. Finally, we concluded that the inhibition of PLA2G4E by Mir504-5p reduced LMP-induced necroptosis, thereby promoting the survival of random-pattern skin flaps.

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.

Infrahyoid myofascial flap transfer for the prevention of concave deformity and gustatory sweating after parotidectomy

ObjectiveConcave deformities and gustatory sweating are the most common complications that cause substantial patient dissatisfaction after parotidectomy. Various surgical methods to prevent these complications have been described. However, effective techniques have not been established, especially in patients with medium- to large-sized parotidectomy defects. We evaluated the utility of infrahyoid myofascial flap reconstruction of parotidectomy defects for the prevention of these complications. MethodsWe conducted a retrospective case series study in patients with a benign or malignant parotid tumor measuring over 4 cm who underwent immediate pedicle infrahyoid myofascial flap reconstruction after total or subtotal parotidectomy or total resection of either the superficial or deep parotid gland at our hospital. Subjective analyses of facial symmetry, postoperative concave deformities of the anterior neck, gustatory sweating, voice disorders, odynophagia, neck scarring in the parotid and anterior neck areas, sensory disorders, pain, and neck stiffness were performed using patient interview data. Objective evaluations of facial symmetry were made by the first or second author. Both analyses were performed after a follow-up of more than six months. Additionally, patient demographic data, clinicopathological factors, parotidectomy and skin incision types, flap survival, and postoperative complications were evaluated. ResultsWe included eight patients (male, n=5; mean age, 69.3 years [range, 37–93 years]). Procedures included total or subtotal parotidectomy (n=4), superficial lobe parotidectomy (n=2), and deep lobe parotidectomy with partial superficial lobe parotidectomy (n=2). Infrahyoid myofascial flaps reached the cranial tip of the parotid defect without tension, and their volume sufficiently filled the parotidectomy defect in all patients. There were no local signs of insufficient blood flow within the transferred flaps.Objective and subjective assessments were made after a mean duration of 1.2 years (range, 0.6-1.8). Postoperatively, no patient subjectively reported facial asymmetry. Objectively, facial symmetry was “good” in four patients and “fair” in four patients. No distinctly visible concave deformity in the parotid or anterior neck area occurred in any patient. Gustatory sweating occurred in one patient; this individual had the largest parotidectomy defect. Only one patient experienced donor site morbidity (mild anterior neck stiffness) related to infrahyoid myofascial flap elevation. ConclusionAlthough complete prevention of gustatory sweating was unsuccessful, infrahyoid myofascial flap reconstruction of medium- to large-sized parotidectomy defects led to postoperative facial symmetry with minimal donor site morbidity.

Effect of memantine on the survival of an ischemic random skin flap and the underlying mechanism

BackgroundSkin flap transplantation is a common wound repair method in orthopedic surgery, but skin flap necrosis remains problematic. Memantine, an excitatory amino acid receptor antagonist, is currently used in the treatment of moderate to severe Alzheimer's disease, due to its ability to promote angiogenesis and reduce oxidative stress. This study investigated the effect of memantine on the survival of random skin flaps in Sprague-Dawley (SD) rats. Materials and methodsThirty six male SD rats were divided into control, high-dose (20 mg/kg per day), and low-dose (10 mg/kg per day) groups and underwent a McFarland flap procedure. Seven days later, the survival of the flap was evaluated, The microvascular density and neutrophil density were measured by hematoxylin and eosin staining. Lead angiography was used to detect angiogenesis, and laser Doppler was used to detect blood perfusion. Expression levels of vascular endothelial growth factor (VEGF), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, Toll-like receptor (TLR) 4, nuclear factor kappa B(NF-κB) and Mitogen-activated protein kinase（MAPK）were detected by immunohistochemistry. Oxidative stress was evaluated by measuring the levels of malondialdehyde (MDA) and superoxide dismutase (SOD). ResultsCompared with the control group, the flap survival area of memantine group, especially the high-dose group, was larger, VEGF expression, microvascular density, angiogenesis, blood perfusion, and superoxide dismutase in the flap were higher in the Memantine-H group than in the Memantine-L and control groups (P < 0.01). In addition, levels of neutrophil density, IL-1β, IL-6, TNF-α, TLR4, NF-κB, MAPK and malondialdehyde decreased significantly in the Memantine-H group (P < 0.01). ConclusionsMemantine can promote the survival of skin flap in rats by improving the blood supply, promoting angiogenesis, inhibiting the inflammatory response, and reducing ischemia-reperfusion injury.

Intravenous Infusion of Mesenchymal Stem Cells Promotes the Survival of Random Pattern Flaps in Rats.

Surgical reconstruction options of soft-tissue defects often include random pattern skin flaps. Flap survival depends on flap size and rotation arc and can be challenging regarding flap perfusion, leading to wound healing complications, insufficient wound coverage, and even flap loss. Therefore, novel approaches that promote skin flap survival are required. Bone marrow-derived mesenchymal stem cells intravenous infusion is therapeutically effective in various experimental disease models by means of multimodal and orchestrated mechanisms including anti-inflammatory and immunomodulatory effects, and by means of microvasculature reestablishment. A modified McFarlane-type rodent skin flap model was used. After skin flap surgery, intravenous infusion of mesenchymal stem cells or vehicle was performed. In vivo optical near-infrared imaging using indocyanine green was performed, followed by histologic analysis, including hematoxylin and eosin and Masson trichrome staining, and gene expression analysis. The flap survival area was greater in the mesenchymal stem cell group. In vivo optical near-infrared perfusion imaging analysis suggested that skin blood perfusion was greater in the mesenchymal stem cell group. Ex vivo histologic analysis demonstrated that the skin structure was more clearly observed in the mesenchymal stem cell group. The dermal thickness was greater in the mesenchymal stem cell group, according to the Masson trichrome staining results. The authors observed a higher expression of fibroblast growth factor 2 mRNA in the tissues of the mesenchymal stem cell group using quantitative reverse-transcription polymerase chain reaction. These results suggest that intravenous infusion of bone marrow-derived mesenchymal stem cells promotes skin survival of random pattern flaps, which is associated with increased blood perfusion and higher expression of fibroblast growth factor 2.

The S1PR1 agonist SEW2871 promotes the survival of skin flap.

Skin flap transfer is an important method to repair and reconstruct various tissue defects; however, avascular necrosis largely affects the success of flap transfer. The sphingosine 1-phosphate receptor 1 (S1PR1) agonist SEW2871 has been proven to ameliorate ischemic injury; however, its effect on flap survival has not been reported. In this study, an experimental skin flap model was established in rats to investigate the roles of SEW2871. The results indicated that SEW2871 greatly increased the survival of the skin flap, alleviated pathological injury, promoted the angiogenesis, and inhibited cells apoptosis in skin flap tissues. SEW2871 activated S1PR1 downstream signaling pathways, including heat shock protein 27 (HSP27), extracellular regulated protein kinases (ERK), and protein kinase B (Akt). In addition, SEW2871 promoted the expression of S1PR1. These findings may provide novel insights for skin flap transfer.

Calcium silicate-human serum albumin composite hydrogel decreases random pattern skin flap necrosis by attenuating vascular endothelial cell apoptosis and inflammation

Random pattern skin flaps are commonly used in plastic surgery to repair skin defects. However, as flap survival mainly relies on blood supply from the distal pedicle and the wound bed, the distal part of the flap is prone to necrosis. Subsequent pathological reactions, including inflammatory reactions, cell apoptosis, and oxidative stress, also aggravate skin flap necrosis. Calcium silicate (CS) has gained attention for its multiple bioactive functions, including promoting angiogenesis and decreasing cell apoptosis, as well as its excellent biocompatibility and safety. Meanwhile, human serum albumin (HSA) hydrogel exhibits excellent drug carrier characteristics and good viscosity for clinical applications. Here, CS was incorporated into HSA hydrogel to form a bioactive composite hydrogel and to control its gelling time. PBS, CS-PBS, HSA hydrogel, and CS-HSA hydrogel were injected under skin flaps on day (-1) and skin flap surgery was performed on day 0. On day 7, the skin flap necrosis rate of the CS-HSA hydrogel group was significantly decreased with increased blood perfusion. Si ions were consistently released from the CS-HSA hydrogel under the skin flap 7 days after operation. Histological staining showed significantly increased CD31+ blood vessels, decreased cell apoptosis, and CD68+ macrophage infiltration. In vitro assays showed that low concentrations of CS extracts sustained cell viability, migration, and tube formation ability of human umbilical vein endothelial cells (HUVECs). CS extracts also decreased HUVEC apoptosis under glucose/oxygen-deprived conditions. Under these conditions, the macrophage inflammatory response decreased. Based on these results, composite CS-HSA hydrogel is suitable for clinical application, and can improve random pattern skin flap survival by attenuating vascular endothelial cell apoptosis and inflammation.

Pseudoginsenoside F11 Enhances the Viability of Random-Pattern Skin Flaps by Promoting TFEB Nuclear Translocation Through AMPK-mTOR Signal Pathway.

Random-pattern skin flap is widely used in tissue reconstruction. However, necrosis occurring in the distal part of the flap limits its clinical application to some extent. Activation of autophagy has been considered as an effective approach to enhance the survival of skin flaps. Pseudoginsenoside F11 (PF11), an ocotillol-type saponin, is an important component of Panax quinquefolium which has been shown to confer protection against cerebral ischemia and alleviate oxidative stress. However, it is currently unknown whether PF11 induces autophagy to improve the survival of skin flaps. In this study, we investigated the effects of PF11 on blood flow and tissue edema. The results of histological examination and western blotting showed that PF11 enhanced angiogenesis, alleviated apoptosis and oxidative stress, thereby improving the survival of the flap. Further experiments showed that PF11 promoted nuclear translocation of TFEB and by regulating the phosphorylation of AMPK. In summary, this study demonstrates that PF11 activates autophagy through the AMPK-TFEB signal pathway in skin flaps and it could be a promising strategy for enhancing flap viability.

The Effect of Locally Infiltrated Platelet-Rich Plasma on Survival of Skin Flaps in Degloving Injuries

Background: Partial- or full-thickness necrosis is normally encountered complication postoperatively in skin flap patients. The chief causes of necrosis are reduced arterial flow, venous insufficiency, or both. Particularly, necrosis of the skin flap occurs in the more distal portion of the flap, if arterial or venous flux insufficient. The other factors owing to the necrosis of skin flap are qualitative and quantitative deficiency of local growth factors (GFs) and lack of regulation of various GFs. Platelet-rich plasma (PRP) is the concentrate of plasma prepared by serial centrifugation and contains high concentrates of platelets. It is rich in various GFs which are essential for wound healing. Materials and Methods: Six patients were included in the study. All the patients had traumatic degloving injuries of lower limbs. After primary cleaning and closure of the flaps, from postoperative day 1, all the flaps were infiltrated with autologous PRP infiltration according to STARS therapy till the wounds healed. Results and Observations: All the wounds healed completely with PRP. PRP sessions required ranged from 4 to 7 with an average of 5.4. There was no need of any additional procedure for wound healing such as serial debridements and skin grafting in any of the patients. Two patients required additional procedures for associated fractures which involved K-wire removal and amputation of the fifth toe. Complications such as infection, abscess, or sinus formation were not seen in any of the patients. After suture removal, the mean ± 2 standard deviation total wound area was 31.5 ± 17.6 cm2, mean necrotic area was 7.75 ± 5 cm2, and mean surviving area was 23.75 ± 13.8 cm2. The mean percentage survival of the flaps was 75.119%. This value is comparable with other studies. Conclusion: In our study, it was found that local autologous PRP infiltration in the skin flap of degloving wounds according to the STARS therapy increases the chances of survival of flap.

Efficacy of Combined in-vivo Electroporation-Mediated Gene Transfer of VEGF, HGF, and IL-10 on Skin Flap Survival, Monitored by Label-Free Optical Imaging: A Feasibility Study.

Preventing surgical flaps necrosis remains challenging. Laser Doppler imaging and ultrasound can monitor blood flow in flap regions, but they do not directly measure the cellular response to ischemia. The study aimed to investigate the efficacy of synergistic in-vivo electroporation-mediated gene transfer of interleukin 10 (IL-10) with either hepatocyte growth factor (HGF) or vascular endothelial growth factor (VEGF) on the survival of a modified McFarlane flap, and to evaluate the effect of the treatment on cell metabolism, using label-free fluorescence lifetime imaging. Fifteen male Wistar rats (290–320 g) were randomly divided in three groups: group-A (control group) underwent surgery and received no gene transfer. Group-B received electroporation mediated hIL-10 gene delivery 24 h before and VEGF gene delivery 24 h after surgery. Group-C received electroporation mediated hIL-10 gene delivery 24 h before and hHGF gene delivery 24 h after surgery. The animals were assessed clinically and histologically. In addition, label-free fluorescence lifetime imaging was performed on the flap. Synergistic electroporation mediated gene delivery significantly decreased flap necrosis (P = 0.0079) and increased mean vessel density (P = 0.0079) in treatment groups B and C compared to control group-A. NADH fluorescence lifetime analysis indicated an increase in oxidative phosphorylation in the epidermis of the group-B (P = 0.039) relative to controls. These findings suggested synergistic in-vivo electroporation-mediated gene transfer as a promising therapeutic approach to enhance viability and vascularity of skin flap. Furthermore, the study showed that combinational gene therapy promoted an increase in tissue perfusion and a relative increase in oxidative metabolism within the epithelium.

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.