The role of Gel-Ppy-modified nerve conduit on the repair of sciatic nerve defect in rat model.

The serious clinical challenge of peripheral nerve injury (PNI) is nerve regeneration. Nerve conduit represents a promising strategy to contribute to nerve regeneration by bridging injured nerve gaps. However, due to a unique microenvironment of nerve tissue, autologous nerves have not been substituted by nerve conduit. Nerve regeneration after nerve conduit implantation depends on many factors, such as conductivity and biocompatibility. Therefore, Gelatin (Gel) with biocompatibility and polypyrrole (Ppy) with conductivity is highly concerned. In this paper, Gel-Ppy modified nerve conduit was fabricated with great biocompatibility and conductivity to evaluate its properties of enhancing nerve regeneration in vivo and in vitro. The proliferation of Schwann cells on Gel-Ppy modified nerve conduit was remarkably increased. Consistent with in vitro results, the Gel-Ppy nerve conduit could contribute to the regeneration of Schwann cell in vivo. The axon diameters and myelin sheath thickness were also enhanced, resulting in the amelioration of muscle atrophy, nerve conduction, and motor function recovery. To explain this interesting phenomenon, western blot results indicated that the Gel-Ppy conduit facilitated nerve regeneration via upregulating the Rap1 pathway to induce neurite outgrowth. Therefore, the above results demonstrated that Gel-Ppy modified nerve conduit could provide an acceptable microenvironment for nerve regeneration and be popularized as a novel therapeutic strategy of PNI.

Fibroblast Growth Factor 9 Inhibited Apoptosis in Random Flap via the ERK1/2-Nrf2 Pathway to Improve Tissue Survival.

BACKGROUND: The application of random pattern skin flaps is limited in plastic surgery reconstruction due to necrosis. Fibroblast growth factor 9 (FGF9) was reported to exert a protective effect against myocardial damage and cerebral ischemia injury, but the impact of FGF9 in random flap survival is still unclear. In this study, we used a mouse model of random flaps to verify that FGF9 can directly increase flap survival area and blood flow intensity by promoting angiogenesis. MATERIALS AND METHODS: In total, 84 male C57BL/6 mice weighing between 22 and 25 g were randomly divided into three groups (n = 28 each group). After skin flap operation, one group served as a control, a treatment group received FGF9, and a treatment group received FGF9+U0126. All flap samples were incised on postoperative day 7. RESULTS: Our results showed that flap survival was significantly increased in the FGF9 group compared with that in the control group. This protective function was restrained by U0126. The results of histopathology, laser Doppler, and fluorescent staining all showed significant increases in capillary count, collagen deposition, and angiogenesis. FGF9 also significantly increased the expression of antioxidant stress proteins SOD1, eNOS, HO-1, vascular marker proteins CD31, VE cadherin, and pericyte marker protein PDGFRß. Western blot showed that the phosphorylation degree of ERK1/2 increased after FGF9 treatment, and the expression of Nrf2, a downstream factor, was u-regulated. Western blot and immunofluorescence results of apoptosis-related proteins cleaved caspase-3, BAX, and Bcl2 showed that FGF9 inhibited apoptosis. ERK inhibitor U01926 reduced the beneficial effects of FGF9 on skin flap survival, including promoting angiogenesis, and showing antiapoptosis and antioxidative stress activities. CONCLUSIONS: Exogenous FGF9 stimulates angiogenesis of random flap and survival of tissue. the impact of FGF9 is closely linked to the prevention of oxidative stress mediated by ERK1/2-Nrf2. In the function of FGF9 in promoting effective angiogenesis, there may be a close interaction in the FGF9-FGFR-PDGFR-ERK-VE cadherin pathway. In particular, PDGFR and VE cadherin may interact.

Sinomenine promotes flap survival by upregulating eNOS and eNOS-mediated autophagy via PI3K/AKT pathway.

Large skin defects and surgical tissue reconstructions are frequently covered utilizing random flaps. The flap has the advantage of being designed according to the size and shape of a surgical wound. However, the necrosis of the distal part of the flap restricts the clinical application of flaps. Sinomenine (SIN) is the major active component of sinomenium acutum. SIN has been demonstrated to inhibit oxidative stress and stimulate autophagy in a cell, animal, and clinical studies. The protective and proliferative effects of sinomenium on HUVECs were evaluated by scratched test, CCK-8, and EDU assays. For the flap survival, we established a mouse random pattern flap model and observed the effects of SIN injected intraperitoneally. The survival area and blood flow intensity of the flap in sinomenium group were significantly increased compared to the control group. Our results demonstrate that SIN promotes flap survival. Sinomenium enhances eNOS expression in the flap and reduces the level of oxidative stress, promotes autophagy flux increase, reduces apoptosis, and promotes angiogenesis. Having a therapeutic benefit of SIN, Autophagy inhibitor 3-MA shows its critical role by reversing the beneficial effects of SIN, and the nitric oxide synthase inhibitor l-NAME both stimulated HUVECs that explore the relationship between autophagy flux and nitric oxide synthase. Furthermore, the mechanism in our study reveals the changes in the signal pathway of PI3K/AKT, the protective effect of SIN during antioxidant activity, the activation of eNOS through PI3K/AKT signaling pathway affects autophagy through the eNOS system, and promote the random flap survival.

Iatrogenic flexor tendon rupture caused by misdiagnosing sarcoidosis-related flexor tendon contracture as tenosynovitis: A case report.

BACKGROUND: Sarcoidosis is a multisystem disease characterized by granuloma formation in various organs. Sarcoidosis-related flexor tendon contractures are uncommon in clinical settings. This contracture is similar to stenosing tenosynovitis and potentially leads to misdiagnosis and mistreatment. Herein, we report a rare case of sarcoidosis-related finger flexor tendon contracture that was misdiagnosed as tenosynovitis. CASE SUMMARY: A 44-year-old woman presented to our department with flexion contracture of the right ring and middle fingers. The patient was misdiagnosed with tenosynovitis and underwent acupotomy release of the A1 pulley of the middle finger in another hospital that resulted in iatrogenic rupture of both the superficial and profundus flexors. Radiological presentation showed multiple sarcoid involvements in the pulmonary locations and ipsilateral forearm. A diagnosis of sarcoidosis was made based on the presence of non-caseating granulomas with tubercles consisting of Langhans giant cells with lymphocyte infiltration on biopsy, and the patient underwent surgical repair for the contracture. After 2 mo, the patient experienced another spontaneous rupture of the repaired middle finger tendon and underwent surgical re-repair. Satisfactory results were achieved at the 10 mo follow-up after reoperation. CONCLUSION: Sarcoidosis-related finger contractures are rare; thus, caution should be exercised when dealing with such patients to avoid incorrect treatment.

Anteroposterior Cannulated Screw Fixation of Coronoid Fractures in Terrible Triad Injuries: A Simple Syringe-guided Technique.

OBJECTIVE: The fixation of the coronoid fractures in terrible triad injuries is quite challenging. In this study, we introduce a minimally invasive technique using a syringe as a guide for insertion of the cannulated screw in an anterior to posterior fashion to fix the coronoid fracture in patients with terrible triad injuries. METHODS: In this retrospective study, clinical data of patients suffering from terrible triad injuries between 2012 and 2019 were analyzed. Fifteen patients with an average age of 38.2 years old (21-56 years) were enrolled in this study, of which 12 were males and three were females. The Regan-Morrey type II and type III coronoid fractures in these patients were treated with cannulated screws, inserted anteriorly using a 1 mL syringe as a guide. Outcome measures included pain, range of motion, stability and daily function using Mayo Elbow Performance scores (MEPs). The anteroposterior and lateral radiographs were used for evaluating a healing fracture. RESULTS: After a mean follow up of 44.2 months (range 13-80), the mean elbow flexion was 128.2°, extension was 12.3°, forearm pronation was 74.6° and supination was 73.6°. A concentric reduction was maintained without severe pain, stiffness, and radiographic evidence of instability in all patients during the follow-up period. The mean MEPs was 89.7 points. CONCLUSION: The anteroposterior cannulated screw fixation via simple syringe guide is a minimally invasive and safe option for surgical treatment of coronoid fractures in terrible triad injuries.

Effectiveness and safety of a less-invasive MCL reconstruction technique for contracted or ossified ligaments in patients with elbow stiffness: An open-label, non-randomised, prospective, multicentre trial in China.

Background: The elbow joint is sensitive to trauma from accidents, sports injuries, and surgical trauma. Some patients develop ossification or contracture of the medial collateral ligament (MCL) after elbow trauma. A less invasive reconstruction of the MCL can be performed after resection of diseased MCL. The biomechanical characteristics of this technique have been demonstrated and validated. However, its clinical effectiveness and safety require further confirmation in clinical practice. Methods: This open-label, non-randomised, prospective, multicentre trial included consecutive patients with elbow stiffness from five orthopaedic centres in China. Patients willing to participate in the study, with elbow stiffness caused by traumatic injury, who had reached skeletal maturity, and who had a range of motion of <100° were eligible for inclusion. Patients with immunological or metabolic causes of elbow stiffness, burns, or central nervous system injuries were excluded. In addition, patients who did not require MCL release and reconstruction after intraoperative release of other structures were also excluded. All patients underwent resection of the diseased MCL part in an open arthrolysis. Medial stability of the elbow was reconstructed using a less invasive MCL reconstruction technique that uses fascia and tendon patches. In this study, the primary outcomes, including stability, Mayo Elbow Performance Score (MEPS), Amadio score, were used to comprehensively evaluate this technique. Outcomes were assessed at 6 weeks, 6 months, and 1 year postoperatively and annually thereafter. This study reports the results of one arm of the trial that has been registered with the Chinese Clinical Trial Registry (chictr.org.cn), ChiCTR-INC-16010019. Findings: Between January 1, 2017 and March 1, 2020, 104 eligible patients were enrolled. The mean follow-up time was 43·47 (95% CI, 41·45 - 45·49) months. Among all 104 patients, 100 (96%) patients who underwent MCL reconstruction retained medial stability at the last follow-up. All outcomes from the last follow-up were used for comparison with the preoperative outcomes. No differences in preoperative and postoperative stability scores were observed (P = 0·7820). Extension, flexion, pronation, and supination of the injured elbow improved significantly (P < 0·0001, P < 0·0001, P < 0·0001, P < 0·0001). The mean range of motion (ROM) and forearm rotational range of motion (FRR) increased by 71·25° (152%) (P < 0·0001) and 30·83° (25%) (P < 0·0001), respectively. Additionally, the Mayo Elbow Performance Score (MEPS) and muscle strength had increased after evaluation at follow-ups (P < 0·0001, P < 0·0001). Drastic pain relief and nerve symptom reduction were observed, as evaluated using VAS scores and Amadio scores, respectively (P < 0·0001, P < 0·0001). Seventeen (16%) patients experienced a recurrence of elbow stiffness of varying severity, but only two patients had poor or fair results. Several common and non-severe complications, including infection in one (1%) patient, new nerve symptoms in seven (7%) patients, new pain in one (1%) patient, fracture in one (1%) patient, and valgus instability in four (4%) patients, were observed and properly treated in this study. Interpretation: The less invasive MCL reconstruction technique using fascia and tendon patches is an effective method for restoring medial stability in patients with elbow stiffness after complete arthrolysis with certain safety. The technique shows prospects for elbow MCL reconstruction in clinical practice. Funding: The study was supported by the National Key Research and Development Program of China (No. 2021YFC2400805), National Natural Science Foundation of China (No. 81830076), Young Elite Scientist Sponsorship Program by Cast (No. YESS20200153), Shanghai Sailing Program (No. 20YF1436000), Shanghai Municipal Science and Technology Commission Foundation (No.19ZR1439200), Municipal Hospital Newly-developing Cutting-edge Technologies Joint Research Program of Shanghai Shenkang Hospital Development Centre (No. SHDC12018130).

Differences between novel hybrid mode flaps and traditional perforator flaps at the level of metabolites using LC-MS.

The multi-territory perforator flaps are widely used in plastic surgery. However, partial necrosis flap in the potential territory remains a challenge to plastic surgeons. We raised a novel "hybrid nourished mode" (HNM) flap based on the multi-territory deep inferior epigastric perforator (DIEP) flap to improve flap survival. Thirty-two rabbits were randomly divided into DIEP and HNM groups. Untargeted metabolic mechanisms between the DIEP and HNM groups were performed using LC-MS under the filter criteria of fold change >20.0 times or <0.05, and variable importance in projection (VIP) value was set at ≥1, P < 0.05. Between the two groups, flap survival, perfusion, microvasculature, histopathology, and immunohistochemistry of CD31 were assessed on post-operative day 7. We screened 16 different metabolites that mainly participated in biosynthesis of secondary metabolites, aminoacyl transfer RNA biosynthesis, phenylalanine metabolism, arginine and proline metabolism, among others. The results of the HNM flaps were higher than those of the DIEP flaps (P < 0.05) in the aspects of flap survival, flap perfusion, and microvasculature. Compared with the DIEP flaps, HNM has a stronger advantage in tissue metabolism. This study provided us with a better understanding and strong evidence in terms of metabolites on how HNM achieves the survival of large multi-territory perforator flaps.

Risk Factors Associated With Misdiagnosis of Digital Glomus Tumor: A Retrospective Cohort Study.

OBJECTIVE: Glomus tumors are benign with unique triad of symptoms; however, the delayed diagnosis of these tumors is common. We investigated the possible risk factors for the misdiagnosis of digital glomus tumors, with an aim to treat these patients on time. METHODS: We conducted a retrospective cohort study of 104 patients with digital glomus tumors from October 2009 to February 2021. Data pertaining to sex, age, tumor locations, symptoms, imaging modalities, and clinical departments visited by the patients were extracted and analyzed through logistic regression. RESULTS: The duration of delayed diagnosis ranged from 3 months to 40 years (mean, 5.5 ± 6.5 years). The total misdiagnosis and recurrence rate are 34.6% and 3.8%, respectively. On the multivariate logistic regression, the misdiagnosis of digital glomus tumor was significantly associated with the clinical departments visited by the patients ( P < 0.001). The risk of misdiagnosis of nonhand surgery department visit is 179.741-fold higher than that of hand surgery department visit. CONCLUSIONS: The misdiagnosis rate of digital glomus tumor was closely related to the clinical departments visited by the patients. Hand surgeons are the first choice for the treatment of the tumor.

Melatonin promotes peripheral nerve repair through Parkin-mediated mitophagy.

Schwann cells (SCs) are the major glial cells in peripheral nervous system. They unsheathe and myelinate axons and play an essential role in peripheral nerve regeneration. Several studies report that Parkin-mediated mitophagy is associated with various diseases. Melatonin promotes proliferation of central glial cells. Little is known about the effect of melatonin and Parkin-mediated mitophagy on peripheral nerve repair. In this study, using a rat model of a peripheral nerve injury (PNI) and in vitro model established by RSC96 cells treated with tert-butyl hydroperoxide (TBHP), we found that Parkin-mediated mitophagy can effectively reduce the production of mitochondrial reactive oxygen species (ROS), maintain the balance of mitochondrial membrane potential, maintain autophagic flux, and inhibit mitochondrial apoptosis. At the same time, we found that the increase of Parkin under stress is a manifestation of the RSC96 cells' resistance to oxidative stress to maintain RSC96 cells' balance. In our experiment, melatonin is similar to a Parkin agonist, up-regulating the expression of Parkin, enhancing all the positive results of Parkin in a stress state, such as inhibiting active oxygen production, maintaining autophagic flux, and inhibiting mitochondrial apoptosis. In addition, we design in vivo experiments to verify in In vitro experiments. In in vivo, melatonin promotes the expression of Parkin, maintains autophagic flux, inhibits apoptosis, promotes myelin regeneration, reduces the regeneration of collagen fibers around damaged tissues, and promotes peripheral nerve repair. When adenovirus was used to down-regulate the expression of Parkin, we found that all the positive effects of melatonin were attenuated. Collectively, these findings indicate that melatonin upregulates Parkin-mediated mitophagy and promotes peripheral nerve repair. The results provide a basis for development of effective drugs for PNI treatment.

Primary closure using a perforator flap-based technique for the treatment of Dupuytren's contracture.

We aim to present a perforator flap-based technique that is useful in the resection and reconstruction of the palmar fascia for the treatment of Dupuytren's contracture with primary closure. A curve incision through the palmar skin radial to the hypothenar area was made. The ulnar side of the palmar skin and the subcutaneous fat was raised to the ulnar side, exposing the palmar fascia. The ulnar palmar digital artery extending from the superficial palmar arch curves distally towards the little finger at a point perpendicular to the fourth interdigital space with parting branches into the subcutaneous fat radial of the flap was carefully identified and preserved, and the Dupuytren's cords were excised. Depending on contracture involvement, additional incision extending from the arc of the palmar incision to the proximal interphalangeal joint is made to raise the digital flap similar to that of the palmar incision. The perforator flap was raised along the hypothenar region in 53 hands of 48 patients, nine women and 39 men, and their age at the time of surgery averaged 56 years. Two patients complained of paresthesia in the ring and little fingers after surgery in 2015, and the symptom had disappeared without further intervention before the latest follow-up in 2017. There was no incidence of skin necrosis, delayed healing, and no recurrence within the follow-up period. This perforator flap-based technique is technically reliable and straightforward with better exposure and easier removal of all the diseased fascia, making it possible for primary healing without skin necrosis and acceptable for the treatment of patients at all stages of the disease.

Exploring the Correlation Between the Regulation of Macrophages by Regulatory T Cells and Peripheral Neuropathic Pain.

OBJECTIVE: Intractable pain after peripheral nerve injury has become a major concern in the field of pain. Current evidence shows that routine medications or surgical treatment is associated with inconsistent results and different curative effects. Stable and effective treatment methods in clinical practice are also lacking. To date, there is no consensus on the pathophysiological mechanisms of pain. The present study investigates the potential regulatory role of regulatory T cells in the differentiation of macrophages on dorsal root ganglion (DRG) and explores the mechanism of nociceptive signals in the signal transfer station. The findings are expected to guide the prevention of various types of peripheral neuropathic pain. METHODS: Thirty-six male Sprague Dawley (SD) rats and 18 male Nude rats, of equal weight (250-300g), were used in this study. The rats were divided into 3 groups: SD rat sciatic nerve transection group (SNT group, n = 18), SD rat nerve transection experimental group (SNT/RAPA group, n = 18) and Nude rat nerve transection experimental group (SNT/NUDE group, n = 18). The behavior related to neuropathic pain of animals were comprehensively evaluated in all groups. Furthermore, we analyzed the degree of neuroma development, histology, gene, and protein expression, and compared their correlation with the ultrastructural changes of M1/M2 type differentiation of macrophages in DRG. RESULTS: Sciatic nerve transection (SNT), induced the aggregation of several types of macrophages in lumbar DRG of SD rats leading to a higher ratio of M1/M2. Following the inhibition of the M1 type polarization of macrophages, axon outgrowth increased significantly. A significantly lower average autotomy score was reported in the SNT/NUDE group (*p < 0.05) and the SNT/RAPA group (@ p < 0.05) as compared to that of the SNT group. The SNT/NUDE group showed no noticeable neuroma formation 30 days after the nerve transection. However, bulbous neuromas were observed in the nerve stumps of both the SNT control and SNT/RAPA groups. Immunofluorescence staining revealed a significant decrease in the proportion of M1/M2 macrophages in lumbar DRG of the SNT/NUDE group (** p < 0.001) and the SNT/RAPA group (@ p < 0.05) compared to the SNT group. The expression of pain-related proteins was also decreased (@ p < 0.05, *p < 0.05,** p < 0.001). Also, the expression of alpha-smooth muscle actin (α-SMA), neurofilament 200 (NF-200), and nerve growth factor low-affinity receptor p75 were significantly down-regulated in the nerve tissue (@ p < 0.05, @@ p < 0.001, ** p < 0.001). CONCLUSION: M1/M2 type differentiation of macrophages on DRG plays a significant role in the formation of traumatic painful neuroma after neurotomy. In combination with our previous study, the results of this study suggest that regulatory T cells reduce the ratio of M1/M2 macrophages and alleviate the pain of neuroma by regulating the polarization direction of macrophages on neuroma. These findings provide key insights into developing new strategies to manage painful neuroma.

A new insight on peripheral nerve repair: the technique of internal nerve splinting.

OBJECTIVE: Neuropathic pain produced by symptomatic neuromas is an important problem after peripheral nerve injury (PNI). End-to-end anastomosis of the nerve stump for PNI is well established but cannot efficiently prevent neuroma-in-continuity formation. METHODS: Sciatic nerve injury was used in the experimental model. Seventy-two rats were randomly divided into four groups: rats with nerve anastomosis sites supported with silicone tubes represented the internal nerve splinting (INS) group (n = 18); rats with end-to-end nerve anastomosis represented control group 1 (CON1) (n = 18); rats with INS and the nerve anastomosis site represented control group 2 (CON2) (n = 18); and rats that underwent the same surgical procedures for skin and muscle operations but without sciatic nerve injury represented the normal group (n = 18). RESULTS: Gross evaluations of the nerve anastomosis sites, gastrocnemius muscle atrophy, axonal regeneration and remyelination, neuropathic pain, and scar hyperplasia of the neuromas were performed, as well as motor function evaluations. Axonal regeneration, remyelination, and gastrocnemius muscle atrophy were similar between the INS group and CON1 (p > 0.05). However, neuropathic pain and scar hyperplasia-as evaluated according to the expression of anti-sigma-1 receptor antibody and anti-α-smooth muscle actin, respectively-and the weight ratios of the neuromas were reduced in the INS group compared with those of CON1 and CON2 (p < 0.05). CONCLUSIONS: Application of INS in nerve repair effectively prevented traumatic neuroma-in-continuity formation and inhibited neuropathic pain without influencing nerve regeneration in rats.

Comprehensive analysis of hypoxia-related genes for prognosis value, immune status, and therapy in osteosarcoma patients.

Osteosarcoma is a common malignant bone tumor in children and adolescents. The overall survival of osteosarcoma patients is remarkably poor. Herein, we sought to establish a reliable risk prognostic model to predict the prognosis of osteosarcoma patients. Patients ' RNA expression and corresponding clinical data were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus databases. A consensus clustering was conducted to uncover novel molecular subgroups based on 200 hypoxia-linked genes. A hypoxia-risk models were established by Cox regression analysis coupled with LASSO regression. Functional enrichment analysis, including Gene Ontology annotation and KEGG pathway analysis, were conducted to determine the associated mechanisms. Moreover, we explored relationships between the risk scores and age, gender, tumor microenvironment, and drug sensitivity by correlation analysis. We identified two molecular subgroups with significantly different survival rates and developed a risk model based on 12 genes. Survival analysis indicated that the high-risk osteosarcoma patients likely have a poor prognosis. The area under the curve (AUC) value showed the validity of our risk scoring model, and the nomogram indicates the model's reliability. High-risk patients had lower Tfh cell infiltration and a lower stromal score. We determined the abnormal expression of three prognostic genes in osteosarcoma cells. Sunitinib can promote osteosarcoma cell apoptosis with down-regulation of KCNJ3 expression. In summary, the constructed hypoxia-related risk score model can assist clinicians during clinical practice for osteosarcoma prognosis management. Immune and drug sensitivity analysis can provide essential insights into subsequent mechanisms. KCNJ3 may be a valuable prognostic marker for osteosarcoma development.

Aligned nanofiber nerve conduits inhibit alpha smooth muscle actin expression and collagen proliferation by suppressing TGF-ß1/SMAD signaling in traumatic neuromas.

Transforming growth factor-beta 1 (TGF-ß1) is a powerful activator of connective tissue synthesis that is strongly associated with the pathophysiology of traumatic neuroma. Previous studies have demonstrated that aligned nanofiber conduits made from silk fibroin and poly (L-lactic acid-co-ε-caprolactone; PLCL) could prevent traumatic neuromas. In the present study, the possible mechanisms of conduits in treating traumatic neuromas were investigated to provide theoretical basis for procedures. Aligned nanofiber conduits were used for nerve capping. Sciatic nerves of Sprague-Dawley rats were used to create an animal model. The present study contains two parts, each including four experimental groups. SB-431542/SRI-011381 hydrochloride was used to suppress/enhance TGF-ß1/SMAD signaling. Part I discussed the connections between traumatic neuroma and the proliferation of alpha smooth muscle actin (α-SMA) and collagen; it also investigated the therapeutic effect of conduits. Part II hypothesized that conduits suppressed TGF-ß1/SMAD signaling. Histological characteristics, quantitative analysis of α-SMA, collagens and signaling-related parameters were assessed and compared among groups one month postoperatively. Results from Part I demonstrated that aligned nanofiber conduits suppressed the expression of α-SMA and collagens; and results from Part II revealed the downregulation of pathway-related proteins, suggesting that the suppression was mediated by TGF-ß1/SMAD signaling. Aligned nanofiber conduits may be effective nerve capping biomaterials. One of the mechanisms involves suppressing TGF-ß1/SMAD signaling. Novel treatments using aligned nanofiber conduits could be developed to manage traumatic neuromas.

Effect of hirudin on arterialized venous flap survival in rabbits.

Arterialized venous flap (AVF) is limited in clinical application because its survival remains inconsistent and its exact survival mechanism is still unclear. Hirudin is an effective thrombin specific inhibitor, which is isolated from the salivary gland secretions of the leech. Our study evaluated the impact of hirudin on the viability of AVFs in rabbits. Thirty-six rabbits were randomly divided into three groups: sham group (physiological perfusion), control group (AVF), and hirudin group (AVF + hirudin). In hirudin group, 20 antithrombin units (ATU) hirudin (2.5 ml) were injected into each flap. In sham group and control group, the same amount of normal saline was injected into each flap. Status of flap survival, water content, vascular perfusion, histopathology, expression of CD34, VEGF, eNOS and HIF-1α were analyzed in each group. Analysis of oxidative stress was performed by measuring the activity of superoxide dismutase (SOD) and malondialdehyde (MDA). Compared with flaps in sham group with physiological perfusion mode, results of survival rate, perfusion status, SOD activity, expression of CD34, VEGF, and eNOS of AVFs in control group were significantly lower, while water content, MDA level and expression of HIF-1α were higher. The flap condition of AVFs injected with hirudin in hirudin group was improved significantly, and the results were similar to sham group. Our findings revealed that hirudin can effectively improve survival of AVF.

The effect of different modes of microneedling technique on random flap survival in rats.

OBJECTIVE: The investigation and practice of physical therapy in flap surgery are still scare. The purpose of this study is to evaluate the impact of different microneedling interventions on survival of random pattern flaps in rats, attempting to determine the optimal microneedling protocols for improvement of flap survival. METHODS: Eighty male Sprague-Dawley rats were randomly divided into four groups, with 20 in each group (group A, B, C, and D). A 3 cm × 9 cm rectangular random flap as the McFarlane flap was adopted in each group. In groups A and B, microneedling treatment was performed before and after surgery, respectively. While animals in group C were received both pre- and postoperative microneedling treatment. Group D was used as a control group, which was only exposed to surgery. Flap survival, flap blood flow, number of capillary formations, the expressions of CD31, CD34, HIF-1α, and vascular endothelial growth factor (VEGF) were detected in each group and compared. RESULTS: On the 7th day postoperatively, significant improvements with microneedling treatment were found in flap survival rate (p = 0.007), blood flow (p = 0.024), the expression levels of CD34 (p = 0.005), and the VEGF (p < 0.01). Furthermore, the VEGF expression level was significantly higher in group B when compared with the other three groups (all p < 0.01). However, there was no significant difference in the number of new blood vessels and other immunohistochemical indicators among the four groups (all p > 0.05). CONCLUSION: Microneedling treatment especially postoperative intervention can significantly improve the survival of random flaps in rats.

The Coverage of Soft-Tissue Defects Around the Foot and Ankle Using Free or Local Flaps: A Comparative Cohort Study.

BACKGROUND: The purpose of this study was to compare the reconstructive outcomes of soft-tissue defects around foot and ankle with local or free flaps and attempt to provide an optimal strategy for these patients in comparison with the conventional guidelines. METHODS: A retrospective review of all continuous patients with foot and ankle reconstruction using different flaps from 2010 to 2018 was performed. Based on the flap types, the patients were divided into 2 groups: local flap group and free flap group. Outcomes were assessed according to the flap survival rate, recipient complications, aesthetic outcomes, and donor-site complications. RESULT: A total of 130 flaps including 47 free flaps and 83 local flaps were collected. There was no difference in flap survival rate between the 2 groups; however, a significant difference in aesthetic outcomes was noted between them: the free flap group presented a better overall aesthetic outcomes in comparison with the local flap group in terms of color and contour match. Moreover, local flaps had more donor-site morbidities including the need for skin grafting and wound infection. CONCLUSIONS: Free flaps in wound coverage of foot and ankle can achieve better outcomes than local flaps in terms of recipient benefits and donor-site compromise with a comparable flap survival rate.

Trans-Cinnamaldehyde Increases Random Pattern Flap Survival Through Activation of the Nitric Oxide Pathway.

BACKGROUND: The application of random pattern skin flaps is limited in plastic surgery reconstruction due to necrosis. Trans-cinnamaldehyde has antibacterial, anticancer, and antioxidant properties. In this study, we aimed to investigate the effect of trans-cinnamaldehyde on skin flap survival and its possible mechanism regarding nitric oxide. MATERIALS AND METHODS: One hundred forty male Sprague-Dawley rats were randomly divided into seven groups (n = 20 each group). After the dorsal flap was raised, different doses of trans-cinnamaldehyde (10, 20, and 30 mg/kg) were immediately given by oral gavage in the three different groups. To assess the possible involvement of the nitric oxide system, NG-nitro-L-arginine methyl ester (L-NAME, a nonselective nitric oxide synthase inhibitor) was used in this study. All flap samples were incised on postoperative day 7. RESULTS: Our results showed that flap survival was increased significantly in the 20 mg/kg (P < 0.001) trans-cinnamaldehyde (TC) group compared to the control group or 30 mg/kg TC group. This protective function was restrained by coadministration of L-NAME with 20 mg/kg TC. The results of histopathology, laser Doppler, arteriography mediated with oxide-gelatine, and fluorescent staining all showed a significant increase in capillary count, collagen deposition, angiogenesis, and flap perfusion. Immunohistochemistry results revealed a significant increase in the expression of CD34, eNOS, and VEGF. CONCLUSION: Trans-cinnamaldehyde increased flap survival through the nitric oxide synthase pathway and contributed to angiogenesis. A concentration of 20 mg/kg trans-cinnamaldehyde was recommended in this study.

A metabolic investigation of arterialized venous flaps in rabbits using mass spectrometry-based metabolomics.

An arterialized venous flap (AVF) is an ideal choice of flap to repair wounds. However, the survival of these flaps remains the source of some concern. This study used metabolomic analysis to investigate the mechanisms underlying survival in AVF flaps in order to guide the clinical application of these flaps. Thirty-six male Japanese rabbits were randomly divided into a sham group and an AVF group. They were used for histology and hemodynamic investigations. Three days after surgery, tissue samples were analyzed by mass spectroscopy-based metabolomics. The results of the study revealed a reduction in blood flow, infiltration of inflammatory cells, and necrosis of flaps in the AVF group. In addition, notable changes were evident in the levels of several metabolites in the AVF group, including lactic acid, acetoacetic acid, inositol phosphate, arachidonic acid, and other metabolites. Our results indicate that the AVF group experienced changes in several biological pathways, including energy metabolism, cell membrane stability, and inflammatory response. There is a significant metabolic difference between AVFs and physiological flaps. The dysregulation in certain metabolites may be related to the specific hemodynamics and insufficient energy metabolism of the AVFs.