Role of Oxygen and Its Radicals in Peripheral Nerve Regeneration: From Hypoxia to Physoxia to Hyperoxia.

Oxygen is compulsory for mitochondrial function and energy supply, but it has numerous more nuanced roles. The different roles of oxygen in peripheral nerve regeneration range from energy supply, inflammation, phagocytosis, and oxidative cell destruction in the context of reperfusion injury to crucial redox signaling cascades that are necessary for effective axonal outgrowth. A fine balance between reactive oxygen species production and antioxidant activity draws the line between physiological and pathological nerve regeneration. There is compelling evidence that redox signaling mediated by the Nox family of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases plays an important role in peripheral nerve regeneration. Further research is needed to better characterize the role of Nox in physiological and pathological circumstances, but the available data suggest that the modulation of Nox activity fosters great therapeutic potential. One of the promising approaches to enhance nerve regeneration by modulating the redox environment is hyperbaric oxygen therapy. In this review, we highlight the influence of various oxygenation states, i.e., hypoxia, physoxia, and hyperoxia, on peripheral nerve repair and regeneration. We summarize the currently available data and knowledge on the effectiveness of using hyperbaric oxygen therapy to treat nerve injuries and discuss future directions.

Therapeutic Potential and Challenges of Mesenchymal Stem Cell-Derived Exosomes for Peripheral Nerve Regeneration: A Systematic Review.

Gap injuries to the peripheral nervous system result in pain and loss of function, without any particularly effective therapeutic options. Within this context, mesenchymal stem cell (MSC)-derived exosomes have emerged as a potential therapeutic option. Thus, the focus of this study was to review currently available data on MSC-derived exosome-mounted scaffolds in peripheral nerve regeneration in order to identify the most promising scaffolds and exosome sources currently in the field of peripheral nerve regeneration. We conducted a systematic review following PRISMA 2020 guidelines. Exosome origins varied (adipose-derived MSCs, bone marrow MSCs, gingival MSC, induced pluripotent stem cells and a purified exosome product) similarly to the materials (Matrigel, alginate and silicone, acellular nerve graft [ANG], chitosan, chitin, hydrogel and fibrin glue). The compound muscle action potential (CMAP), sciatic functional index (SFI), gastrocnemius wet weight and histological analyses were used as main outcome measures. Overall, exosome-mounted scaffolds showed better regeneration than scaffolds alone. Functionally, both exosome-enriched chitin and ANG showed a significant improvement over time in the sciatica functional index, CMAP and wet weight. The best histological outcomes were found in the exosome-enriched ANG scaffold with a high increase in the axonal diameter and muscle cross-section area. Further studies are needed to confirm the efficacy of exosome-mounted scaffolds in peripheral nerve regeneration.

[Management of patients with complex ear deformities]. / Prise en charge des patients présentant des déformations complexes du pavillon de l'oreille.

Complex ear reconstruction requires specialized multidisciplinary care. Most patients present with microtia, often associated with hearing disorders. The management of these disorders is a priority, and reconstruction of the external ear remains optional. Nowadays, auricular reconstruction is based on the subcutaneous implantation of either autologous cartilage or an allogeneic implant. Autologous reconstruction requires highly specialized surgical expertise and involves harvesting rib cartilage but carries a lower risk of exposure compared to allogeneic implants. Both techniques yield good results with a high success rate and have a positive impact on the social functioning and daily life of patients.

La reconstruction complexe du pavillon auriculaire nécessite une prise en charge multidisciplinaire spécialisée. La majorité des patients nécessitant ce geste présentent une microtie, souvent associée à des troubles de l'audition. La prise en charge de ceux-ci est prioritaire et la reconstruction du pavillon reste facultative. Aujourd'hui, la reconstruction du pavillon se base sur l'implantation sous-cutanée d'une maquette de cartilage autologue ou d'un implant allogène. La reconstruction autologue demande une expertise chirurgicale hautement spécialisée et nécessite un prélèvement de cartilage costal mais présente un risque d'exposition inférieur par rapport à l'implant allogène. Les deux techniques permettent d'atteindre de bons résultats avec un taux de réussite élevé et un effet positif sur le fonctionnement social et le quotidien des patients.

Extensive skin necrosis following total hip arthroplasty performed through the direct anterior approach.

BACKGROUND: Total hip arthroplasty is a widely performed surgical procedure, which enables patients to regain mobility, alleviates pain, and improves overall quality of life. Periarticular multimodal drug infiltration (PAI) is increasingly being used as an effective postoperative pain management, decreasing the systemic consumption of opioids. Extensive postoperative skin necrosis without a deep joint infection as a complication of total hip arthroplasty with PAI has not yet been described. CASE PRESENTATION: A 71-year-old patient who underwent total hip arthroplasty of the right hip for primary osteoarthritis through the Direct Anterior Approach presented postoperatively a large area of necrotic skin at the incision. Joint infection was excluded. An extensive debridement was performed and the tissue defect was reconstructed by a pedicled anterolateral thigh flap. The skin maintained a satisfactory appearance at 1 year postoperatively, and the hip was pain-free with restored ranges of motion. The patient was able to walk with no support and without limitation. CONCLUSION: We address the possible risk factors, discuss the use of epinephrine in PAI and explore possible treatment options for such a complication.

Mesenchymal Stem Cells in Nerve Tissue Engineering: Bridging Nerve Gap Injuries in Large Animals.

Cell-therapy-based nerve repair strategies hold great promise. In the field, there is an extensive amount of evidence for better regenerative outcomes when using tissue-engineered nerve grafts for bridging severe gap injuries. Although a massive number of studies have been performed using rodents, only a limited number involving nerve injury models of large animals were reported. Nerve injury models mirroring the human nerve size and injury complexity are crucial to direct the further clinical development of advanced therapeutic interventions. Thus, there is a great need for the advancement of research using large animals, which will closely reflect human nerve repair outcomes. Within this context, this review highlights various stem cell-based nerve repair strategies involving large animal models such as pigs, rabbits, dogs, and monkeys, with an emphasis on the limitations and strengths of therapeutic strategy and outcome measurements. Finally, future directions in the field of nerve repair are discussed. Thus, the present review provides valuable knowledge, as well as the current state of information and insights into nerve repair strategies using cell therapies in large animals.

[Total knee arthroplasty and soft tissue defect: what are the reconstructive options?] / Prothèse totale de genou et lésion des tissus mous : quelles options pour la reconstruction ?

Wound healing issues are not rare after total knee arthroplasty. While most patients heal with local wound care, a minority is susceptible to develop serious complications such as peri-prosthetic joint infection. If direct closure is not feasible, we recommend a multidisciplinary approach based on the ortho-plastic model to determine the optimal wound closure strategy. Negative pressure wound therapy can be used while waiting for definitive coverage to optimise wound environment. Medial gastrocnemius flap is considered as the gold standard procedure for peri-prosthetic substance loss around the knee.

Les problèmes de cicatrisation ne sont pas rares après l'implantation d'une prothèse totale de genou. La plupart des patients guérissent avec des soins locaux mais une minorité d'entre eux peut développer des complications redoutables allant jusqu'à l'infection périprothétique. Hormis les situations pour lesquelles une fermeture directe de la cicatrice chirurgicale peut être réalisée, nous recommandons une approche multidisciplinaire basée sur le modèle de l'ortho-plastique afin de déterminer la stratégie de reconstruction la plus adaptée. La thérapie par pression négative peut être utilisée pour conditionner la plaie en vue d'un geste de couverture définitive. Le lambeau gastrocnémien médial est considéré comme la procédure de référence pour les pertes de substance périprothétique du genou.

[Management of symptomatic breast hypertrophy and reduction mammaplasty]. / Prise en charge de l'hypertrophie mammaire symptomatique et réduction mammaire.

Breast hypertrophy (macromastia) can cause various symptoms correlated with excessive breast volume and is usually associated with breast ptosis. Symptomatic macromastia can constitute a heavy burden on patient's global health. While conservative therapy does not allow for long term relief, breast reduction mammaplasty is an effective and safe treatment. Multiple techniques have been described, but all rely on common principles. Measures can be taken to lower surgical complications rates and implemented by primary care physicians in collaboration with the plastic surgery approach.

L'hypertrophie mammaire symptomatique se définit comme un ou plusieurs symptômes en lien avec un volume mammaire augmenté, en général associé à une ptose mammaire. Elle peut avoir un impact majeur sur la santé globale des patientes. Alors que les traitements conservateurs ne permettent pas de soulager les patientes à long terme, la réduction mammaire chirurgicale est un traitement efficace et sûr. De nombreuses techniques ont été décrites, mais reposent sur des principes communs. Certaines mesures permettent une diminution des risques de complications chirurgicales et peuvent être entreprises conjointement à la prise en charge en chirurgie plastique.

Extending the limits of the anterior tibial artery as the recipient vessel for around the knee and proximal lower extremity defect reconstruction using the free anterolateral thigh and gracilis flap.

PURPOSE: The aim is to describe a technique with orthograde dissection of the anterior tibial artery (ATA) used as the recipient vessel for the end-to-end (ETE) anastomosis in defect reconstruction around the knee and for proximal/middle third leg defects with free anterolateral thigh (ALT) and gracilis flaps. PATIENTS AND METHODS: Between March 2009 and May 2014, 22 patients undergoing lower extremity reconstruction were evaluated. Of those, 4 patients were included. The locations of injury were 3 defects around the knee and 1 defect at the proximal and middle third of the lower leg (mean defect size 18 x 8.5 cm and a range of 17-20 x 5-10 cm). There were 2 cases after trauma and 2 cases with infection. Two free gracilis and 2 free ALT flaps were performed of equal size to the defects. The mean flap pedicle length was 11 cm (range of 7-16 cm) and the mean length of the mobilized recipient vessels was 10.5 cm (range of 6-14 cm). RESULTS: One flap loss (ALT) occurred, requiring a salvage procedure with a latissimus dorsi flap, whereas wound dehiscence at the donor site and a hematoma below the ALT flap was observed in 2 cases, requiring small revision. After a mean follow-up of 52 months (range of 38-87 months), there was stable soft tissue coverage in all patients. CONCLUSION: By orthograde dissection of the ATA, an adequate vessel length and size may be achieved, improving arc of rotation to successfully cover more distant defects.

From Bedside to Bench: The Effect of Muscular Denervation on Fat Grafting to the Breast by Comparing Take Rate, Quality, and Longevity.

BACKGROUND: Autologous fat grafting (AFG) to the breast is a frequent procedure in aesthetic and reconstructive surgery. Despite pure volume gain, questions remain regarding the engraftment rate, quality, and longevity. Little is known about the role of recipient tissue or innervation of the grafted area. OBJECTIVES: The goal of this study was to determine the optimal recipient layer and muscular pretreatment of AFG. METHODS: Fat was grafted to the breast, pectoralis muscle, or adjacent subcutaneous tissue of 42 rats. Nerve treatment included excision of a nerve segment, botulinum toxin (BTX) injection, or no treatment. Magnetic resonance imaging (MRI) and histological workup were carried out after 2 and 6 weeks. RESULTS: Six weeks after AFG, the proportion of viable fat cells within the grafted fat stayed high (median, [IQR]: 81% [72% to 85%]). The signs of inflammation decreased over time. Intramuscular grafting with intact nerves had a decreasing effect on the viability of the grafted cells compared with subcutaneous treatment (-10.21%; 95% confidence interval [-21.1 to 0.68]). CONCLUSIONS: If utilized on an intact nerve, intramuscular injection may lead to inferior results. If the nerve was cut or treated with BTX; however, intramuscular injection tends to be superior. These findings may prove interesting for future studies and eventual clinical application.

Evaluation of the Neo-umbilicus Cutaneous Sensitivity Following Abdominoplasty.

BACKGROUND: Abdominal cutaneous sensitivity loss after abdominoplasty is an undesirable outcome. However, little is known in the literature about sensitivity changes of the neo-umbilicus after abdominoplasty. The aim of this study was to evaluate post-abdominoplasty cutaneous sensitivity of the neo-umbilicus using clinical, quantitative, and reproducible methods. METHODS: Patients who underwent abdominoplasty were included, whereas the control group consisted of healthy volunteers with similar demographic characteristics but who did not undergo abdominoplasty. The umbilicus was divided into five zones, and superficial tactile sensitivity and spatial orientation were assessed subjectively (score 1-4) and objectively (Semmes-Weinstein monofilament examination). RESULTS: Twenty patients (45 ± 12 years) operated on consecutively between April 2012 and May 2016 and 14 healthy volunteers in the control group (39 ± 9 years) could be included. Although there were statistically significant differences (p = 0.0005) in the average cutaneous pressure thresholds between the control group (0.4 g/mm2, range 0.07-2 g/mm2) and the study group (0.4 g/mm2, range 0.07-4 g/mm2), patient satisfaction after a mean follow-up of 33 ± 16 months (range 10-62 months) was acceptable (mean satisfaction score 1.8 ± 0.7). Furthermore, spatial perceptions were precise in all patients and similar to the control group. CONCLUSION: Our long-term results indicate that spontaneous reinnervation of the neo-umbilicus after abdominoplasty together with accurate spatial orientation can occur. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. 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 .

Gluteal Augmentation Techniques: A Comprehensive Literature Review.

Background: Many studies of gluteal augmentation techniques have been published in recent decades, including case reports, retrospective and prospective case series, and multicenter survey reviews. However, to date, there has been no study of the overall complications or satisfaction rates associated with the broad spectrum of techniques. Objectives: The authors performed a comprehensive literature review to determine outcomes and complications of gluteoplasty techniques, including patient satisfaction. Methods: A search on PubMed/Medline was performed for clinical studies involving gluteal augmentation techniques. A priori criteria were used to review the resulting articles. Results: Fifty-two studies, published from 1969 through 2015, were included - representing 7834 treated patients. Five gluteal augmentation techniques were identified from these studies: gluteal augmentation with implants (n = 4781), autologous fat grafting (n = 2609), local flaps (n = 369), hyaluronic acid gel injection (n = 69), and local tissue rearrangement (n = 6). The overall complication rates of the most commonly utilized techniques were: 30.5% for gluteal augmentation with implants, 10.5% for autologous fat grafting, and 22% for local flaps. Patients' satisfaction was reported as consistently high for all the five techniques. Conclusions: Implant-based gluteal augmentation is associated with high patients' satisfaction despite a high complication rate, while autologous fat grafting is associated with the lowest complication rate yet including serious major complications such as fat embolism. Local flaps and local tissue rearrangements are the ideal procedures in case of massive weight loss patients. A paucity of data is available for hyaluronic acid gel injections, which appear to be effective but temporary and expensive.

Nipple Reconstruction After Autologous or Expander Breast Reconstruction: A Multimodal and 3-Dimensional Analysis.

BACKGROUND: Little is known about the influence of the underlying tissue as donor for nipple-areola complex (NAC) reconstruction. Also, there is a complete lack of knowledge about the fate of nipple volume. OBJECTIVES: The goal of this retrospective, single-institution study was to analyze a case series after nipple reconstruction using a multimodal evaluation including 3-dimensional (3D) laser scanner analyses. METHODS: Unilateral mastectomy patients after either expander-based or autologous breast reconstruction using the skate flap were included. NAC caliper measurement of nipple and areola size was performed. 3D laser scanner analysis (Minolta Vivid 900) was used to calculate nipple volume, measurement of nipple, and areolar projection and diameter. Sensitivity was evaluated using the Semmes Weinstein test and patient satisfaction by a visual analog scale (VAS 1-10). RESULTS: A total of 10 patients were included in the expander group and 12 patients were included in the flap group. After a median follow-up period of 32 months in the expander group and 34 months in the flap group, non-contact 3D laser surface scanning revealed a difference in projection of 55 to 60% compared to the contralateral side. The contraction in all 3 dimensions led to a dramatic difference in nipple volume with 12 ± 8% (flap reconstructions) and 12 ± 7% (expander reconstructions). Sensitivity of the areola showed better values after expander-based reconstruction. Despite the significant discrepancy in nipple volume and projection as well as areolar diameter, overall patient satisfaction was acceptable (VAS 4.1 ± 3.5). CONCLUSIONS: Volume assessment revealed a massive asymmetry to the intact nipple but not between expander and flap reconstructions. Although asymmetry of the areola and nipple remains, patient satisfaction is acceptable. LEVEL OF EVIDENCE 4.

Adipose-Derived Stromal Cells from Lipomas: Isolation, Characterisation and Review of the Literature.

OBJECTIVE: The aim of this study was to characterize adipose-derived stromal cells (ADSCs) from patients diagnosed with multiple symmetric lipomatosis (MSL) in order to obtain potentially new insights into the pathophysiology, pathogenesis and treatment of this disease. METHODS: Cells from the stromal vascular fraction were analysed by the colony-forming efficiency assay and flow cytometry using standard markers. Moreover, the power of adipogenic plasticity was evaluated. Finally, a literature review was performed from 1982 to 2015 using the US National Institutes of Health's PubMed database. RESULTS: Three European-descent patients diagnosed with either MSL type I or II could be identified for analysis. The resulting mean colony-forming efficiency assay was 14.3 ± 5%. Flow-cytometric analysis of the ADSCs revealed high levels of CD34 (70 ± 9%), CD45 (37 ± 13%) and CD73 (55.8 ± 14%), whereas low levels of CD31 (16.8 ± 14%) and CD105 (5.8 ± 0.7%) were detected. Furthermore, ADSCs showed a strong adipogenic potential, which is in line with the literature review. The stem cell pool in lipoma shows several alterations in biological activities, such as proliferation, apoptosis and stemness. CONCLUSIONS: ADSCs from lipoma may be interesting in the application of regenerative medicine. We discuss possible molecular treatment options to regulate their activities at the source of the MSL.

Impact of platelet rich plasma and adipose stem cells on lymphangiogenesis in a murine tail lymphedema model.

BACKGROUND: Lymphedema is an underdiagnosed pathology which in industrialized countries mainly affects cancer patients that underwent lymph node dissection and/or radiation. Currently no effective therapy is available so that patients' life quality is compromised by swellings of the concerned body region. This unfortunate condition is associated with body imbalance and subsequent osteochondral deformations and impaired function as well as with an increased risk of potentially life threatening soft tissue infections. METHODS: The effects of PRP and ASC on angiogenesis (anti-CD31 staining), microcirculation (Laser Doppler Imaging), lymphangiogenesis (anti-LYVE1 staining), microvascular architecture (corrosion casting) and wound healing (digital planimetry) are studied in a murine tail lymphedema model. RESULTS: Wounds treated by PRP and ASC healed faster and showed a significantly increased epithelialization mainly from the proximal wound margin. The application of PRP induced a significantly increased lymphangiogenesis while the application of ASC did not induce any significant change in this regard. CONCLUSIONS: PRP and ASC affect lymphangiogenesis and lymphedema development and might represent a promising approach to improve regeneration of lymphatic vessels, restore disrupted lymphatic circulation and treat or prevent lymphedema alone or in combination with currently available lymphedema therapies.

The Combined Pedicled Anterolateral Thigh and Vastus Lateralis Flap as Filler for Complex Perineal Defects.

Extensive defects of the pelvis and genitoperineal region are a reconstructive challenge. We discuss a consecutive series of 25 reconstructions with the pedicled anterolateral thigh (ALT) flap including muscle part of the vastus lateralis (VL) in 23 patients from October 1999 to September 2012.Only surface defects larger than 100 cm and reconstructions by composite ALT + VL were included in this retrospective analysis. Of the 23 patients, 19 underwent oncologic resection, whereas 4 cases presented Fournier gangrene. Three patients did not reach 6 months of follow-up and were excluded from further data analysis. Among the remaining 20 patients (22 reconstructions), average follow-up period was 14 months (range, 10-18 months). Patient's average age was 60 years. Average size of the defect was 182 cm.Postoperative complications included 1 (4.5%) flap necrosis out of 22 raised flaps, 1 partial flap necrosis after venous congestion, and 2 cases where a complementary reconstructive procedure was performed due to remaining defect or partial flap failure. In 6 cases, peripheral wound dehiscence (27%) was treated by debridement followed by split-thickness skin graft or advancement local flaps. Defect size was significantly related to postoperative complications and increased hospital stay, especially in those patients who underwent preoperative radiotherapy. At the end of the follow-up period, a long-term and satisfactory coverage was obtained in all patients without functional deficits.This consecutive series of composite ALT + VL flap shows that, in case of extended defects, the flap provides an excellent and adjustable muscle mass, is reliable with minimal donor-site morbidity, and can even be designed as a sensate flap.

Local flap therapy for the treatment of pressure sore wounds.

The aim of this study was to analyse the effectiveness of an interdisciplinary cooperation between conservative and surgical disciplines for the treatment of pressure sores (PS). From January 2004 to December 2005, a single-centre study was performed with paraplegic and tetraplegic patients presenting with PS grades III-V. Outcome measures were defect size, grade, method of reconstruction, complication and recurrence rate as well as average length of hospitalisation. A total of 119 patients aged 22-84 years with totally 170 PS were included. The most common PS were located in the ischial region (47%), followed by the sacral (18%), trochanteric (11%), foot (9%) and the malleolar (8%) regions. Defect sizes ranged between 4 and 255 cm(2) . Grade IV was the most common PS (68%), followed by grade III (30%) and grade V (2%) PS. For wound closure, fasciocutaneous flaps were used most frequently (71%), followed by skin grafts (10%) and myocutaneous flaps (7%). Postoperative follow-up ranged between 6 and 38 months. The overall complication and recurrence rate was 26% and 11%, respectively. If no complication occurred, the average duration of hospitalisation stay after the first debridement was 98 ± 62 days. In conclusion, our treatment concept is reliable, effective and results in a low recurrence rate. The complication rate, even though favourable when compared with the literature, still needs to be improved.

Laser scanning evaluation of atrophy after autologous free muscle transfer.

Denervated muscle tissue undergoes morphologic changes that result in atrophy. The amount of muscle atrophy after denervation following free muscle transfer has not been measured so far. Therefore, the amount of muscle atrophy in human free muscle transfer for lower extremity reconstruction was measured in a series of 10 patients. Three-dimensional laser surface scanning was used to measure flap volume changes 2 weeks as well as 6 and 12 months after the operation. None of the muscles transferred was re-innervated.All muscles healed uneventfully without signs of compromised perfusion resulting in partial flap loss. The muscle volume decreased to 30 ± 4% and 19 ± 4% 6 and 12 months, respectively, after the operation, ie, the volume decreased by approximately 80% within a 12-month period.Denervated free muscle flap tissue undergoes massive atrophy of approximately 80%, mostly within the first 6 months.

Second free radial forearm flap for urethral reconstruction after partial flap necrosis of tube-in-tube phalloplasty with radial forearm flap: a report of two cases.

We present a salvage procedure to reconstruct the neo-urethra after partial flap necrosis occurring in free radial forearm flap (RFF) phalloplasty for sex reassignment surgery. Two cases of tube-in-tube phalloplasty using a free sensate RFF are described in which partial flap necrosis occurred involving the complete length of the neo-urethra and a strip of the outer lining of the neo-phallus. Neo-urethra-reconstruction was performed with a second RFF from the contralateral side providing well-vascularized tissue. No flap-related complications were observed. Twelve months postoperatively, both patients were able to void while standing. A satisfactory aesthetic appearance of the neo-phallus could be preserved with an excellent tactile and erogenous sensitivity. Using this technique, we successfully salvaged the neo-urethra and reconstructed the outer lining of the neo-phallus

Bone propeller flap: a staged procedure.

The ideal reconstruction technique for complex defects of the lower limb consists of replacing tissue with similar tissue in an attempt to achieve a good functional result. A 23-year-old white male sustained a crush injury with a grade IIIB open ankle dislocation. After open reduction and fixation, the patient developed severe osteomyelitis at the tibiotalar joint requiring a staged and radical debridement with a substantial combined soft tissue and bony defect over the distal tibia, fibula, and talus area. The reconstructive approach consisted of a modified model of the propeller flap, implementing the spare part concept in a 2-stage procedure using a prefabricated and vascularized "double-barrel" fibular graft. At 17 months postoperatively, a plain radiograph showed bony union with complete and stable coverage of the soft tissue defect. The patient was fully weightbearing. In conclusion, there is evidence to suggest that the established concept of a soft tissue propeller flap can be implemented on bone.