Correction of asymmetric pectus excavatum using a virtually designed silicone implant.

BACKGROUND: An extended asymmetric funnel chest deformity with the breast gland located in the thoracic mold can lead to a fictitious aplasia of the breast. The authors termed this condition "pseudo-Amazon syndrome" because the breast tissue and the pectoralis muscle are fully developed. METHODS: This report presents a detailed technical approach to the fabrication of a precise-fitting custom-made silicone implant. The design of the implant was achieved using a computed tomography (CT) data set and rapid prototyping. The volumes of the "hidden" and the normal breasts measured preoperatively by processing the CT data were similar. These volumes were compared with the breast volumes measured by three-dimensional photography 4 years postoperatively to assess the predictability of the volume congruency. The silicone implant was surgically placed in the epicostal plane and extended almost over the right hemithorax. RESULTS: The implantation was performed without the necessity of further trimming. Both the surgeon and the patient rated the aesthetic and functional long-term result as good in terms of symmetry and the possibility of exercise without restrictions. The final breast volume of the surgically treated side was 95 % of the volume of the normal contralateral breast. CONCLUSION: The described method reduces the operation time and the operative trauma by primary implant fit. However, the method is rather elaborate and the production process is expensive. This in turn reduces the generation of proceeds to a minimum. LEVEL OF EVIDENCE V: 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 .

Neo-Omphaloplasty within a Vertical Scar: The Double Trapezium Flap Technique.

Background: Various techniques for neo-omphaloplasty (or umbilicoplasty/umbiliconeoplasty) have been established in recent decades. However, when the omphaloplasty must be integrated into a vertical scar, most of these techniques are unsuitable. Method: We established a technique comprising two "cross-border" trapezium flaps that come together in a key-lock fashion to be applicable for umbilical reconstruction in vertical scars. Between 2020 and 2023, we performed the double trapezium flap technique in 11 patients requiring abdominal wall correction due to previous operations resulting in the loss of the original navel and a vertical midline scar. The follow-up period was 12 months. Results: We encountered two minor wound healing disorders not involving the omphaloplasty. One patient experienced a more severe wound healing complication involving the vertical scar and the lower flap of the neo-umbilicus. No cases of umbilical flattening or detachment of the anchorage stitches were detected. Patients ranked the aesthetic outcomes as "excellent" (n = 9) or "good" (n = 2). Physicians ranked the results as "excellent" (n = 7), "good" (n = 4), and "average" (n = 1). Conclusions: For the selected patients, this technique appears to be a good and reliable option to create a natural looking neo-umbilicus, creating sufficient umbilical depth with minimal scarring. While a study population of 11 patients is hardly enough to endorse a new technique, appropriate cases are comparatively rare and very specific.

How to Treat a Cyclist's Nodule?-Introduction of a Novel, ICG-Assisted Approach.

BACKGROUND: Perineal nodular induration (PNI) is a benign proliferation of the soft tissue in the perineal region that is associated with saddle sports, especially road cycling. The etiology has not been conclusively clarified; however, repeated microtrauma to the collagen and subcutaneous fat tissue by pressure, vibration and shear forces is considered a mechanical pathomechanism. In this context, chronic lymphedema resulting in the development of fibrous tissue has been suggested as an etiological pathway of PNI. The primary aim of this study was to introduce and elucidate a novel operative technique regarding PNI that is assisted by indocyanine green (ICG). In order to provide some context for this approach, we conducted a comprehensive review of the existing literature. This dual objective aimed to contribute to the existing body of knowledge while introducing an innovative surgical approach for managing PNI. METHODS: We reviewed publications relating to PNI published between 1990 and 2023. In addition to the thorough review of the literature, we presented our novel surgical approach. We described how this elaborate approach for extensive cases of PNI involves surgical excision combined with tissue doubling and intraoperative ICG visualization for exact lymphatic vessel obliteration to minimize the risk of recurrence based on the presumed context of lymphatic congestion. RESULTS: The literature research yielded 16 PubMed articles encompassing 23 cases of perineal nodular induration (PNI) or cyclist's nodule. Of these, 9 cases involved females, and 14 involved males. Conservative treatment was documented in 7 cases (30%), while surgical approaches were reported in 16 cases (70%). Notably, a limited number of articles focused on histopathological or radiological characteristics, with a shortage of structured reviews on surgical treatment options. Only two articles provided detailed insights into surgical techniques. Similarly to the two cases of surgical intervention identified in the literature research, the post-operative recovery in our ICG assisted surgical approach was prompt, meaning a return to cycling was possible six weeks after surgery. At the end of the observation period (twelve months after surgery), regular scar formation and no signs of recurrence were seen. CONCLUSION: We hope that this article draws attention to the condition of PNI in times of increasing popularity of cycling as a sport. We aimed to contribute to the existing body of knowledge through our thorough review of the existing literature while introducing an innovative surgical approach for managing PNI. Due to the successful outcome, the combination of tissue doubling, intraoperative ICG visualization and postoperative negative wound therapy should be considered as a therapeutic strategy in cases of large PNI.

How Reliable Is Breast Volume Assessment When the Patient Is Lying Flat?-Volumetric Assessment of Breast Volume Using a Vectra H2 Handheld Device in Different Positions.

(1) Background: Three-dimensional (3D) volumetric assessment is receiving increased recognition in breast surgery. It is commonly used for preoperative planning and postoperative control with the patient standing in an upright position. Recently, intraoperative use was evaluated with patients in the supine position. The aim of this prospective study was to evaluate the volumetric changes in 3D surface imaging depending on the patient's position. (2) Methods: 3D volumetric analysis was performed using a Vectra-H2 device with patients in standing, sitting, and supine positions. A total of 100 complete datasets of female breasts were included in the study. The measured volumes of each evaluated breast (n = 200) were compared between the three positions. (3) Results: The mean difference between the 3D volumetric assessments of the sitting and standing positions per breast was 7.15 cc and, thus, statistically insignificant (p = 0.28). However, the difference between supine and standing positions, at 120.31 cc, was significant (p < 0.01). (4) Conclusions: The 3D volumetric assessment of breasts in the supine position did not statistically correlate with the validated assessment of breast volume in the standing position while breast volume in the sitting position is reliable and correlates with the assessment of a standing patient. We conclude that intraoperative volumetric assessment should be performed with patients in an upright sitting position.

Improving symmetry of nipple-areola complex (NAC) position in reduction mammoplasty using laser level projection.

BACKGROUND: Symmetrical height of the nipple-areola complex (NAC) is a key factor in the perception of breast symmetry. For preoperative markings, we mainly rely on conventional anthropometric measurements of distances in correlation to anatomical landmarks. In this study, we evaluated whether the use of a class 2 laser projection water level would lead to better symmetry of nipple height in reduction mammoplasty procedures when used for preoperative planning. METHODS: We analysed 100 patients undergoing reduction mammoplasty with a supero-medial pedicle and wise-pattern skin resection. We compared the bilateral differences in nipple height of the last 50 reduction mammoplasty procedures before using the laser projection water level (group A; no laser) with the first 50 reduction mammoplasties after implementation of this device (group B; laser). The follow-up period was 12 months. RESULTS: A total of 48 patients were included in group A and 44 patients in group B. Patient demographics, mean resection weight and complications did not differ statistically significantly. Nipple height differences were significantly lower in group B (laser), measuring 0.22 ± 0.20 cm (0-0.9; n = 44), than those in group A (no laser; p < 0.001), measuring 0.61 ± 0.28 cm (0.2-1.2; n = 49). CONCLUSION: Using laser level projection helped improve nipple height symmetry in reduction mammoplasty. We consider a difference of more than 1 cm in nipple height to be unacceptable in aesthetic reduction mammoplasty. This simple tool facilitates preoperative markings, and we find it to be safe, quick to install and very helpful in daily practice.

Hypoxic pre-conditioned adipose-derived stem/progenitor cells embedded in fibrin conduits promote peripheral nerve regeneration in a sciatic nerve graft model.

Recent results emphasize the supportive effects of adipose-derived multipotent stem/progenitor cells (ADSPCs) in peripheral nerve recovery. Cultivation under hypoxia is considered to enhance the release of the regenerative potential of ADSPCs. This study aimed to examine whether peripheral nerve regeneration in a rat model of autologous sciatic nerve graft benefits from an additional custom-made fibrin conduit seeded with hypoxic pre-conditioned (2% oxygen for 72 hours) autologous ADSPCs (n = 9). This treatment mode was compared with three others: fibrin conduit seeded with ADSPCs cultivated under normoxic conditions (n = 9); non-cell-carrying conduit (n = 9); and nerve autograft only (n = 9). A 16-week follow-up included functional testing (sciatic functional index and static sciatic index) as well as postmortem muscle mass analyses and morphometric nerve evaluations (histology, g-ratio, axon density, and diameter). At 8 weeks, the hypoxic pre-conditioned group achieved significantly higher sciatic functional index/static sciatic index scores than the other three groups, indicating faster functional regeneration. Furthermore, histologic evaluation showed significantly increased axon outgrowth/branching, axon density, remyelination, and a reduced relative connective tissue area. Hypoxic pre-conditioned ADSPCs seeded in fibrin conduits are a promising adjunct to current nerve autografts. Further studies are needed to understand the underlying cellular mechanism and to investigate a potential application in clinical practice.

Evaluation of Intraoperative Volumetric Assessment of Breast Volume Using 3D Handheld Stereo Photogrammetric Device.

Methods for assessing three-dimensional (3D) breast volume are becoming increasingly popular in breast surgery. However, the precision of intraoperative volumetric assessment is still unclear. Until now, only non-validated scanning systems have been used for intraoperative volumetric analyses. This study aimed to assess the feasibility, handling, and accuracy of a commercially available, validated, and portable device for intraoperative 3D volumetric evaluation. All patients who underwent breast surgery from 2020 to 2022 were identified from our institutional database. Intraoperative 3D volumetric assessments of 103 patients were included in this study. Standardized 3D volumetric measurements were obtained 3 months postoperatively to compare the intraoperatively generated volumetric assessment. All of the study participants were women with a mean age of 48.3 ± 14.7 years (range: 20-89). The mean time for intraoperative volumetric assessment was 8.7 ± 2.6 min. The postoperative 3D volumetric assessment, with a mean volume of 507.11 ± 206.29 cc, showed no significant difference from the intraoperative volumetric measurements of 504.24 ± 276.61 cc (p = 0.68). The mean absolute volume difference between the intraoperative simulations and postoperative results was 27.1 cc. Intraoperative 3D volumetric assessment using the VECTRA H2 imaging system seems to be a feasible, reliable, and accurate method for measuring breast volume. Based on this finding, we plan to investigate whether volumetric objective evaluations will help to improve breast symmetry in the future.

How Useful Is the SSN-Nipple Distance? An Analytical Questionnaire Survey on Anthropometric Measurements for the Aesthetically Ideal Positioning of the Nipple-Areolar Complex.

Several studies have attempted to identify the optimal anthropometric measurement for the aesthetically ideal positioning of the nipple-areolar complex. However, no standardised solutions and measurements for planning surgical procedures have been reached. The aim of this study is to identify the optimal anthropometric measurement between the suprasternal notch (SSN)-nipple distance and mid-clavicle (MC)-nipple distance for the aesthetic position of the nipple-areola complex (NAC) on the breast. A detailed online survey was sent to 300 board-certified plastic surgeons and residents of plastic surgery departments of hospitals in German, Austrian, and Swiss. A similar survey was also provided to 100 patients who had planned or had already undergone breast surgery. All participants were asked to rank the attractiveness of a series of women's breasts in images with different NAC position measurements. The images showed breasts from two different measurements and distances: all the breasts had equal dimensions and proportions and the same areola size. Complete datasets were obtained from 203 of the 300 board-certified plastic surgeons and residents of plastic surgery departments in German-speaking countries (recall 68%) and from 100 patients. The majority of doctors and patients find a symmetrical breast with a mirrored position of the nipple-areola complex more attractive than a non-symmetrical breast. In cases with minor measurement differences, such as 0.5 cm (SSN vs. MC), there is no relevant difference in the breast symmetry. However, at larger distances, the MC-to-nipple distance is superior for achieving aesthetically appealing symmetry compared with the SSN-to-nipple distance. Using the MC-to-nipple distance seems to be superior for correct nipple positioning than the SSN-to-nipple distance and is a valuable preoperative measurement option for breast symmetry with correct nipple height. Further studies on this topic involving a more general population should be conducted to confirm the improvements in perception with the preoperative measurements using the anatomical landmarks.

Vascular endothelial growth factor (VEGF165) plus basic fibroblast growth factor (bFGF) producing cells induce a mature and stable vascular network--a future therapy for ischemically challenged tissue.

BACKGROUND: Vascular endothelial growth factor (VEGF)(165) induces formation of immature blood vessels with increased permeability. In this study, we used a cell-based gene-transfer model of fibroblasts to investigate the effects of a combined in vivo treatment consisting of the VEGF165 and basic fibroblast growth factor (bFGF) proteins on ischemic and non-ischemic tissues. MATERIALS AND METHODS: After controlled in vitro adenoviral transfection we transplanted fibroblasts into either healthy tissue, or into an ischemic skin flap model at different tissue locations and at different time points. Subsequent protein expression and angiogenic effects were measured using ELISA, PCR, immunohistology, planimetry, and microangiography. RESULTS: Transfected fibroblasts temporarily produced VEGF(165) and bFGF. After transdermal implantation we found an up-regulation of genes encoding for both factors in tissue samples. The combined transplantation of VEGF(165) and bFGF modified cells increased the number of sm-actin+/CD31+ blood vessels and reduced necrosis by 25%. The number of functional blood vessels increased over a period of 168 d even in healthy tissue. CONCLUSIONS: We achieved stable vessel growth in healthy tissue by inducing a temporary overexpression of VEGF(165) and bFGF and improved the survival of ischemic tissue. One possible mechanism for the latter observation is the stabilization of VEGF(165)-induced hyperpermeable vessels by a bFGF-mediated pericytial recruitment of smooth muscle cells.

[Liposuction with consequences: what to consider when using prilocaine]. / Folgenreiche Liposuktion ­ was man im Umgang mit Prilocain beachten sollte.

Aetiologically, prilocaine-induced methaemoglobinaemia is a rare form of acquired methaemoglobinaemia, which occurs rarely in the first place. The following report highlights a potentially dangerous complication arising after application of prilocaine during liposuction.A young female visited the Accident and Emergency Department following a pre-syncopal fall. As a consequence of her fall, she experienced debilitating wrist pain and exhibited a laceration on her chin. She had undergone liposuction of the lower extremity as an outpatient approximately 12 hours earlier and received regional anaesthesia in the process. A large volume of an anaesthetic solution containing prilocaine had been injected into the tissue.The patient was normotensive and slightly tachycardic and had oxygen saturations of 90 % on room air. She was cyanotic and her lips were pale. Initial arterial blood gas analysis showed a methaemoglobin fraction, which was increased significantly to 10.9 %. Conventional radiography confirmed the presence of a minimally dislocated distal radius fracture. Following subsequent oxygen therapy over a four-hour period, the patient's methaemoglobin level dropped to 6 %, her lip cyanosis abated and her vital parameters stabilised. The laceration of her chin was sutured and her wrist immobilised in a split plaster brace. After a 12-hour hospital stay, the patient was discharged. At her six-week follow-up appointment, the fracture had healed and both the functional and cosmetic aspects of her chin wound were adequate. We hope that this report draws the attention of emergency care personnel to the possible diagnosis of prilocaine-induced methaemoglobinaemia after liposuction and encourages more general discussions around the use of prilocaine.

Open Carpal Tunnel Release Under WALANT - Suitable for All Ages?

Purpose: Wide-awake local anesthesia with no tourniquet (WALANT) as a walk-in procedure has become a standard technique in open carpal tunnel release (OCTR) and continues to replace the long-established intravenous regional anesthesia with a tourniquet (IVRA/"bier-block") in our clinic. The aim of this study was to compare patient satisfaction with either WALANT or IVRA/"bier-block" and define subgroups that are particularly suited for either of the two procedures. We hypothesized that older patients would prefer IVRA because of a shorter period of postoperative surveillance. Methods: In this retrospective study we evaluated patient satisfaction with either WALANT or IVRA using an adjusted questionnaire on a standard Swiss grading system (from 1 = insufficient/very strong pain to 6 = excellent/no pain). Secondary outcomes included postoperative pain or satisfaction with the tourniquet and quality of postoperative care. Results: For the 176 patients (WALANT, n = 109; IVRA, n = 67) included in the study, there was high patient satisfaction with both procedures (WALANT, 5.5/6; IVRA, 5.5/6). Patients aged 80 years and older had significantly less postoperative pain after WALANT (WALANT, 5.8/6 vs IVRA, 4.9/6). Conclusions: Patients aged 80 years and older had significantly less postoperative pain after WALANT than that after IVRA. Here, sarcopenia may have contributed to the prolonged discomfort after tourniquet application. Immediate postoperative discharge after WALANT did not negatively affect older patients. Clinical relevance: For OCTR, WALANT as a walk-in procedure is a safe and comfortable alternative to IVRA, which is commonly planned with short postoperative surveillance. Both anesthesia techniques are suitable for all ages and sexes but based on this study we recommend WALANT as a tourniquet-free operation in older patients.

Prepectoral versus subpectoral implant-based breast reconstruction after skin-sparing mastectomy or nipple-sparing mastectomy (OPBC-02/ PREPEC): a pragmatic, multicentre, randomised, superiority trial.

INTRODUCTION: The emphasis on aesthetic outcomes and quality of life (QoL) has motivated surgeons to develop skin-sparing or nipple-sparing mastectomy (SSM/ NSM) for breast cancer treatment or prevention. During the same operation, a so-called immediate breast reconstruction is performed. The breast can be reconstructed by positioning of a breast implant above (prepectoral) or below (subpectoral) the pectoralis major muscle or by using the patients' own tissue (autologous reconstruction). The optimal positioning of the implant prepectoral or subpectoral is currently not clear. Subpectoral implant-based breast reconstruction (IBBR) is still standard care in many countries, but prepectoral IBBR is increasingly performed. This heterogeneity in breast reconstruction practice is calling for randomised clinical trials (RCTs) to guide treatment decisions. METHODS AND ANALYSIS: International, pragmatic, multicentre, randomised, superiority trial. The primary objective of this trial is to test whether prepectoral IBBR provides better QoL with respect to long-term (24 months) physical well-being (chest) compared with subpectoral IBBR for patients undergoing SSM or NSM for prevention or treatment of breast cancer. Secondary objectives will compare prepectoral versus subpectoral IBBR in terms of safety, QoL and patient satisfaction, aesthetic outcomes and burden on patients. Total number of patients to be included: 372 (186 per arm). ETHICS AND DISSEMINATION: This study will be conducted in compliance with the Declaration of Helsinki. Ethical approval has been obtained for the lead investigator's site by the Ethics Committee 'Ethikkommission Nordwest- und Zentralschweiz' (2020-00256, 26 March 2020). The results of this study will be published in a peer-reviewed medical journal, independent of the results, following the Consolidated Standards of Reporting Trials standards for RCTs and good publication practice. Metadata describing the type, size and content of the datasets will be shared along with the study protocol and case report forms on public repositories adhering to the FAIR (Findability, Accessibility, Interoperability, and Reuse) principles. TRIAL REGISTRATION NUMBER: NCT04293146.

Non-viral VEGF(165) gene therapy--magnetofection of acoustically active magnetic lipospheres ('magnetobubbles') increases tissue survival in an oversized skin flap model.

Adenoviral transduction of the VEGF gene in an oversized skin flap increases flap survival and perfusion. In this study, we investigated the potential of magnetofection of magnetic lipospheres containing VEGF(165)-cDNA on survival and perfusion of ischemic skin flaps and evaluated the method with respect to the significance of applied magnetic field and ultrasound. We prepared perfluoropropane-filled magnetic lipospheres ('magnetobubbles') from Tween60-coated magnetic nanoparticles, Metafectene, soybean-oil and cDNA and studied the effect in an oversized random-pattern-flap model in the rats (n= 46). VEGF-cDNA-magnetobubbles were administered under a magnetic field with simultaneously applied ultrasound, under magnetic field alone and with applied ultrasound alone. Therapy was conducted 7 days pre-operative. Flap survival and necrosis were measured 7 days post-operatively. Flap perfusion, VEGF-protein concentration in target and surrounding tissue, formation and appearance of new vessels were analysed additionally. Magnetofection with VEGF-cDNA-magnetobubbles presented an increased flap survival of 50% and increased flap perfusion (P < 0.05). Without ultrasound and without magnetic field, the effect is weakened. VEGF concentration in target tissue was elevated (P < 0.05), while underlying muscle was not affected. Our results demonstrate the successful VEGF gene therapy by means of magnetobubble magnetofection. Here, the method of magnetofection of magnetic lipospheres is equally efficient as adenoviral transduction, but has a presumable superior safety profile.

Vaginal carcinoma in a female-to-male transsexual.

INTRODUCTION: Sex reassignment surgery (SRS) can be considered a reasonable and secure treatment for transsexualism, today. Because the population of patients who have received SRS is growing steadily, it can be expected that the number of patients who present with diseases specific to their original gender will increase as well. AIM: In female-to-male transsexuals, vaginal cancer has not been reported so far. This article reports, to our knowledge, the first case of a female-to-male transsexual who developed vaginal cancer. METHODS: Eighteen years after receiving female-to-male SRS, the patient presented with vaginal cancer, which infiltrated rectum and bladder and also showed involvement of inguinal lymph nodes. Surgery consisted of an anterior and posterior pelvic demolition and extended lymphadenectomy with preservation of the penoid and reconstruction of the pelvic defect with multiple flaps. RESULTS: The tumor was removed completely (R0), and 2 years after surgery, the patient has no signs or symptoms of tumor recurrence and enjoys good quality of life. CONCLUSIONS: In SRS patients, diseases of their original gender should always be considered and patients should be encouraged to participate in screening programs. When choosing the surgical approach for SRS, the risks for developing cancer from remaining structures of the genetic gender should be considered. Of course, removal of e.g., ovaries, cervix and vagina, will prevent cancer of these structures. When it comes to surgery in SRS patients with malignancies, an interdisciplinary approach should be chosen.

Fibrin glue displays promising in vitro characteristics as a potential carrier of adipose progenitor cells for tissue regeneration.

Adipose-derived multipotent stem/progenitor cells (ASPCs) were shown to be ideal candidates for cell-based regenerative therapies. Yet, despite their huge potential, successful clinical applications are still rare. It was suggested that the efficacy of ASPCs at the recipient site depends on the vehicle of cell delivery. In this study, for preparation of a murine critical-size nerve defect model, we assessed the commercially available fibrin gel (ARTISS) as a potential cell carrier. In a thorough in vitro analysis, we investigated cell-fibrin interactions and analyzed the distribution and the long-term behavior of ASPCs cultivated in fibrin gel under normoxic and hypoxic conditions. ASPCs attached to the surface of a thin fibrin layer (two-dimensional condition) and spread with the abundant formation of actin stress fibers. Cells cultured within a fibrin matrix (three-dimensional condition) displayed a uniform distribution and formed interconnected networks while exhibiting strong cell-matrix interactions. Using time-lapse analysis, cells were found to migrate out of the gel and subsequently proliferated robustly both under hypoxic and normoxic conditions. During 14 days of culture in fibrin gel, ASPCs showed high viability, metabolic, and remodeling activities. At the end of the culture period, the fibrin matrix was degraded entirely accompanied by an upregulation of matrix metalloproteinases. In conclusion, fibrin gel stands out as a valuable biomaterial for delivering vital and active cells to damaged tissues. As a direct proof, ASPCs carried in a fibrin matrix will be evaluated in a murine critically sized peripheral nerve repair model.

Validation of a novel animal model for sciatic nerve repair with an adipose-derived stem cell loaded fibrin conduit.

Despite the regenerative capabilities of peripheral nerves, severe injuries or neuronal trauma of critical size impose immense hurdles for proper restoration of neuro-muscular circuitry. Autologous nerve grafts improve re-establishment of connectivity, but also comprise substantial donor site morbidity. We developed a rat model which allows the testing of different cell applications, i.e., mesenchymal stem cells, to improve nerve regeneration in vivo. To mimic inaccurate alignment of autologous nerve grafts with the injured nerve, a 20 mm portion of the sciatic nerve was excised, and sutured back in place in reversed direction. To validate the feasibility of our novel model, a fibrin gel conduit containing autologous undifferentiated adipose-derived stem cells was applied around the coaptation sites and compared to autologous nerve grafts. After evaluating sciatic nerve function for 16 weeks postoperatively, animals were sacrificed, and gastrocnemius muscle weight was determined along with morphological parameters (g-ratio, axon density & diameter) of regenerating axons. Interestingly, the addition of undifferentiated adipose-derived stem cells resulted in a significantly improved re-myelination, axon ingrowth and functional outcome, when compared to animals without a cell seeded conduit. The presented model thus displays several intriguing features: it imitates a certain mismatch in size, distribution and orientation of axons within the nerve coaptation site. The fibrin conduit itself allows for an easy application of cells and, as a true critical-size defect model, any observed improvement relates directly to the performed intervention. Since fibrin and adipose-derived stem cells have been approved for human applications, the technique can theoretically be performed on humans. Thus, we suggest that the model is a powerful tool to investigate cell mediated assistance of peripheral nerve regeneration.

Vascular endothelial growth factor gene therapy improves nerve regeneration in a model of obstetric brachial plexus palsy.

The treatment of obstetric brachial plexus palsy has been limited to conservative therapies and surgical reconstruction of peripheral nerves. In addition to the damage of the brachial plexus itself, it also leads to a loss of the corresponding motoneurons in the spinal cord, which raises the need for supportive strategies that take the participation of the central nervous system into account. Based on the protective and regenerative effects of VEGF on neural tissue, our aim was to analyse the effect on nerve regeneration by adenoviral gene transfer of vascular endothelial growth factor (VEGF) in postpartum nerve injury of the brachial plexus in rats. In the present study, we induced a selective crush injury to the left spinal roots C5 and C6 in 18 rats within 24 hours after birth and examined the effect of VEGF-gene therapy on nerve regeneration. For gene transduction an adenoviral vector encoding for VEGF165 (AdCMV.VEGF165) was used. In a period of 11 weeks, starting 3 weeks post-operatively, functional regeneration was assessed weekly by behavioural analysis and force measurement of the upper limb. Morphometric evaluation was carried out 8 months post-operatively and consisted of a histological examination of the deltoid muscle and the brachial plexus according to defined criteria of degeneration. In addition, atrophy of the deltoid muscle was evaluated by weight determination comparing the left with the right side. VEGF expression in the brachial plexus was quantified by an enzyme-linked immunosorbent assay (ELISA). Furthermore the motoneurons of the spinal cord segment C5 were counted comparing the left with the right side. On the functional level, VEGF-treated animals showed faster nerve regeneration. It was found less degeneration and smaller mass reduction of the deltoid muscle in VEGF-treated animals. We observed significantly less degeneration of the brachial plexus and a greater number of surviving motoneurons (P < 0·05) in the VEGF group. The results of this study confirmed the positive effect of VEGF-gene therapy on regeneration and survival of nerve cells. We could demonstrate a significant improvement on the motor-functional as well as on the histomorphological level. However, increased vascularization of the nerve tissue caused by VEGF does not seem to be the major reason for these effects. The clinical use of adenoviral VEGF-gene therapy in the newborn cannot be justified so far.