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The placenta is the first embryonic organ, representing the connection between the embryo and the mother, and is therefore necessary for the embryo’s growth and survival. To meet the ever-growing need for nutrient and gas exchange, the maternal spiral arteries undergo extensive remodeling, thus increasing the uteroplacental blood flow by 16-fold. However, the insufficient remodeling of the spiral arteries can lead to severe pregnancy-associated disorders, including but not limited to pre-eclampsia. Insufficient endovascular trophoblast invasion plays a key role in the manifestation of pre-eclampsia; however, the underlying processes are complex and still unknown. Classical histopathology is based on two-dimensional section microscopy, which lacks a volumetric representation of the vascular remodeling process. To further characterize the uteroplacental vascularization, a detailed, non-destructive, and subcellular visualization is beneficial. In this study, we use light sheet microscopy for optical sectioning, thus establishing a method to obtain a three-dimensional visualization of the vascular system in the placenta. By introducing a volumetric visualization method of the placenta, we could establish a powerful tool to deeply investigate the heterogeneity of the spiral arteries during the remodeling process, evaluate the state-of-the-art treatment options, effects on vascularization, and, ultimately, reveal new insights into the underlying pathology of pre-eclampsia.

Background: Pediatric liver transplantation (LT) is the treatment of choice for children with end-stage liver disease and in certain cases of hepatic malignancies. Due to low case numbers, a technically demanding procedure, the need for highly specialized perioperative intensive care, and immunological, as well as infectious, challenges, the highest level of interdisciplinary cooperation is required. The aim of our study was to analyze short- and long-term outcomes of pediatric LT in our center. Methods: We conducted a retrospective single-center analysis of all liver transplantations in pediatric patients (≤16 years) performed at the Department of Surgery, Charité – Universitätsmedizin Berlin between 1991 and 2021. Three historic cohorts (1991–2004, 2005–2014 and 2015–2021) were defined. Graft- and patient survival, as well as perioperative parameters were analyzed. The study was approved by the institutional ethics board. Results: Over the course of the 30-year study period, 212 pediatric LTs were performed at our center. The median patient age was 2 years (IQR 11 years). Gender was equally distributed (52% female patients). The main indications for liver transplantation were biliary atresia (34%), acute hepatic necrosis (27%) and metabolic diseases (13%). The rate of living donor LT was 25%. The median cold ischemia time for donation after brain death (DBD) LT was 9 h and 33 min (IQR 3 h and 46 min). The overall donor age was 15 years for DBD donors and 32 years for living donors. Overall, respective 1, 5, 10 and 30-year patient and graft survivals were 86%, 82%, 78% and 65%, and 78%, 74%, 69% and 55%. One-year patient survival was 85%, 84% and 93% in the first, second and third cohort, respectively (p = 0.14). The overall re-transplantation rate was 12% (n = 26), with 5 patients (2%) requiring re-transplantation within the first 30 days. Conclusion: The excellent long-term survival over 30 years showcases the effectiveness of liver transplantation in pediatric patients. Despite a decrease in DBD organ donation, patient survival improved, attributed, besides refinements in surgical technique, mainly to improved interdisciplinary collaboration and management of perioperative complications.

Background: Pediatric liver transplantation (LT) is the treatment of choice for children with end-stage liver disease and in certain cases of hepatic malignancies. Due to low case numbers, a technically demanding procedure, the need for highly specialized perioperative intensive care, and immunological, as well as infectious, challenges, the highest level of interdisciplinary cooperation is required. The aim of our study was to analyze short- and long-term outcomes of pediatric LT in our center. Methods: We conducted a retrospective single-center analysis of all liver transplantations in pediatric patients (≤16 years) performed at the Department of Surgery, Charité – Universitätsmedizin Berlin between 1991 and 2021. Three historic cohorts (1991–2004, 2005–2014 and 2015–2021) were defined. Graft- and patient survival, as well as perioperative parameters were analyzed. The study was approved by the institutional ethics board. Results: Over the course of the 30-year study period, 212 pediatric LTs were performed at our center. The median patient age was 2 years (IQR 11 years). Gender was equally distributed (52% female patients). The main indications for liver transplantation were biliary atresia (34%), acute hepatic necrosis (27%) and metabolic diseases (13%). The rate of living donor LT was 25%. The median cold ischemia time for donation after brain death (DBD) LT was 9 h and 33 min (IQR 3 h and 46 min). The overall donor age was 15 years for DBD donors and 32 years for living donors. Overall, respective 1, 5, 10 and 30-year patient and graft survivals were 86%, 82%, 78% and 65%, and 78%, 74%, 69% and 55%. One-year patient survival was 85%, 84% and 93% in the first, second and third cohort, respectively (p = 0.14). The overall re-transplantation rate was 12% (n = 26), with 5 patients (2%) requiring re-transplantation within the first 30 days. Conclusion: The excellent long-term survival over 30 years showcases the effectiveness of liver transplantation in pediatric patients. Despite a decrease in DBD organ donation, patient survival improved, attributed, besides refinements in surgical technique, mainly to improved interdisciplinary collaboration and management of perioperative complications.

Sun radiation is indispensable to our health, however, a long term and high exposure could lead to erythema, premature skin aging and promotion of skin tumors. An underlying pathomechanism is the formation of free radicals. First, reactive oxygen species (*OH, *O2-) and then, secondary lipid oxygen species (C centered radicals, CCR) are formed. A high amount of free radicals results in oxidative stress with subsequent cell damage. In dermatological research different skin models are used, however, comparative data about the cutaneous radical formation are missing. In this study , the radical formation in porcine-, (SKH-1) murine-, human- ex vivo skin and reconstructed human skin (RHS) were investigated during simulated sun irradiation (305–2200 nm), with X-band EPR spectroscopy. The amount of radical formation was investigated with the spin probe PCA exposed to a moderate sun dose below one minimal erythema dose (MED, ~25 mJ/cm2 UVB) in all skin models. Furthermore, the *OH and *CCR radical concentrations were measured with the spin trap DMPO within 0–4 MED (porcine-, human skin and RHS). The highest amount of radicals was found in RHS followed by murine and porcine , and the lowest amount in human ex vivo skin. In all skin models , more *OH than CCR radicals were found at 0–4 MED. Additionally, this work addresses the limitations in the characterization with the spin trap DMPO. The measurements have shown that the most comparable skin model to in vivo human skin could differ depending on the focus of the investigation. If the amount of radial production is regarded, RHS seems to be in a similar range like in vivo human skin. If the investigation is focused on the radical type, porcine skin is most comparable to ex vivo human skin, at an irradiation dose not exceeding 1 MED. Here, no comparison to in vivo human skin is possible.

Perineal defects following the resection of anorectal malignancies are a reconstructive challenge. Flaps based on the rectus abdominis muscle have several drawbacks. Regional perforator flaps may be a suitable alternative. We present our experience of using the gluteal fold flap (GFF) for reconstructing perineal and pelvic defects. We used a retrospective chart review and follow-up examinations focusing on epidemiological, oncological (procedure and outcome), and therapy-related data. This included postoperative complications and their management, length of hospital stay, and time to heal. Twenty-two GFFs (unilateral n = 8; bilateral n = 7) were performed in 15 patients (nine women and six men; anal squamous cell carcinoma n = 8; rectal adenocarcinoma n = 7; mean age 65.5 + 8.2 years) with a mean follow-up time of 1 year. Of the cases, 73.3% were a recurrent disease. Microscopic tumor resection was achieved in all but one case (93.3%). Seven cases had no complications (46.7%). Surgical complications were classified according to the Clavien-Dindo system (grades I n = 2; II n = 2; IIIb n = 4). These were mainly wound healing disorders that did not affect mobilization or discharge. The time to discharge was 22 + 9.9 days. The oncological outcomes were as follows: 53.3% of the patients had no evidence of disease, 20% had metastatic disease, 20% had local recurrent disease, and one patient (6.7%) died of other causes. The GFF is a robust, reliable flap suitable for perineal and pelvic reconstruction. It can be raised quickly and easily, has an acceptable complication rate and donor site morbidity, and does not affect the abdominal wall.

Introduction: In pediatric liver transplantation (pLT), hepatic artery thrombosis (HAT) is associated with inferior transplant outcome. Hepatic artery reconstruction (HAR) using an operating microscope (OM) is considered to reduce the incidence of HAT. Methods: HAR using an OM was compared to a historic cohort using surgical loupes (SL) in pLT performed between 2009 and 2020. Primary endpoint was the occurrence of HAT. Secondary endpoints were 1-year patient and graft survival determined by Kaplan-Meier analysis and complications. Multivariate analysis was used to identify independent risk factors for HAT and adverse events. Results: A total of 79 pLTs were performed [30 (38.0%) living donations; 49 (62.0%) postmortem donations] divided into 23 (29.1%) segment 2/3, 32 (40.5%) left lobe, 4 (5.1%) extended right lobe, and 20 (25.3%) full-size grafts. One-year patient and graft survival were both 95.2% in the OM group versus 86.2% and 77.8% in the SL group (p = .276 and p = .077). HAT rate was 0% in the OM group versus 24.1% in the SL group (p = .013). One-year patient and graft survival were 64.3% and 35.7% in patient with HAT, compared to 93.9% and 92.8% in patients with no HAT (both p < .001). Multivariate analysis revealed HAR with SL (p = .022) and deceased donor liver transplantation (DDLT) (p = .014) as independent risk factors for HAT. The occurrence of HAT was independently associated with the need for retransplantation (p < .001) and biliary leakage (p = .045). Conclusion: In pLT, the use of an OM is significantly associated to reduce HAT rate, biliary complications, and graft loss and outweighs the disadvantages of delayed arterial perfusion and prolonged warm ischemia time (WIT).

Abdominal wall closure after pediatric liver transplantation (pLT) in infants may be hampered by graft-to-recipient size discrepancy. Herein, we describe the use of a porcine dermal collagen acellular graft (PDCG) as a biological mesh (BM) for abdominal wall closure in pLT recipients. Patients

Activation of non-neuronal microglia is thought to play a causal role in spinal processing of neuropathic pain. To specifically investigate microglia-mediated effects in a model of neuropathic pain and overcome the methodological limitations of previous approaches exploring microglia function upon nerve injury, we selectively ablated resident microglia by intracerebroventricular ganciclovir infusion into male CD11b-HSVTK–transgenic mice, which was followed by a rapid, complete, and persistent (23 weeks) repopulation of the CNS by peripheral myeloid cells. In repopulated mice that underwent sciatic nerve injury, we observed a normal response to mechanical stimuli, but an absence of thermal hypersensitivity ipsilateral to the injured nerve. Furthermore, we found that neuronal expression of calcitonin gene–related peptide (CGRP), which is a marker of neurons essential for heat responses, was diminished in the dorsal horn of the spinal cord in repopulated mice. These findings identify distinct mechanisms for heat and mechanical hypersensitivity and highlight a crucial contribution of CNS myeloid cells in the facilitation of noxious heat.

Numerous studies have employed tape stripping (TS) or cyanoacrylate stripping (CS) to induce skin barrier disruption of the stratum corneum (SC) in human and porcine skin. However, the thickness of the remaining SC and the respective changes of the skin permeability have been rarely quantified. By using high-resolution multiphoton tomography, about 5 µm thick SC was found remaining on human skin after the performance of 30 times TS or 2 times CS. 50 tape strips or 4 times CS removed the entire human SC, but on porcine skin 2–3 µm thick SC was still left. TS can only reach the transition zone between the SC and the stratum granulosum because of the limited adhesion, whereas CS was able to remove viable skin layers. Permeation investigations on porcine skin revealed that the apparent permeability coefficient of the hydrophilic nitroxide spin 2,5,5-Tetramethyl-1-pyrrolidinyloxy-3-carboxylic acid increased 15-, 18-, and 21-fold when the SC amount remaining in the skin was 30%, 16%, and 8%, respectively. It is recommended to use at most 30 times TS or 3 times CS to obtain ex vivo barrier-disrupted skin that mimics diseased skin. The study provides quantitative information for the utility of TS and CS in skin penetration research.

The method of choice for treatment of sacral chordomas is en bloc tumor removal via sacrectomy or sacral amputation in varying degrees depending on the initial tumor extent. Besides local tumor control, the preservation of neurological function is equally important to minimize postoperative bladder and bowel dysfunction. Removal of sacral tumors is complicated by the complex regional anatomy of the pelvis and the surrounding visceral and retroperitoneal structures. We aim to describe the surgical workflow for a fully navigated high sacral amputation facilitated by integration of an intraoperative computed tomography (iCT)-based spinal navigation system. An iCT-based spinal navigation system (AIRO® CT scanner, Brainlab AG, Feldkirchen, Germany) was used to perform intraoperative navigation with an image-guidance system and infrared tracking camera (BrainLab CurveTM, Brainlab AG, Feldkirchen, Germany) in combination with the spinal navigation set by Brainlab (Brainlab AG, Feldkirchen, Germany) to perform a fully navigated high sacral amputation. We demonstrate the successful implementation of iCT-based spinal navigation during high sacral amputation and the key advantages of this technique throughout the surgery. iCT-based spinal navigation is a useful complementing technique for en bloc high sacral amputations that renders the surgery safer and more accurate.

Background Breast cancer is the most common cancer affecting women in Germany. Despite breast-conserving therapy (BCT) being carried out in almost 70% of cases, a high number of women still require complete mastectomy. Prophylactic mastectomy is also indicated for women with a BRCA 1/2 gene mutation. In addition to implant-based heterologous breast reconstruction, autologous breast reconstruction using a DIEP flap has been found to be beneficial, particularly for patients who had prior radiotherapy. This study aims to show that DIEP flap reconstruction surgery is the method of choice for autologous breast reconstruction with a low rate of complications. Patients and Methods Autologous breast reconstruction using a DIEP flap was performed in 1124 patients between July 2004 and December 2014. Retrospective study criteria included potential risk factors such as age, BMI, smoking, chemotherapy and/or radiotherapy, and comorbidities as well as outcome parameters such as postoperative complications. Outcomes were evaluated with a mean follow-up of 24 months. Results A total of 1124 patients underwent 1274 free DIEP flap breast reconstructions, of which 150 were bilateral reconstructions. The primary indication was previous mastectomy in 785 cases, followed by prior implant-based reconstruction in 265 cases. The total flap loss rate was 0.6%. Postoperative surgical revision for abdominal wall hernia was required in 0.2% of cases. The group with a higher BMI and the group of smokers had significantly higher complication rates. Elderly patients (> 65 years), patients who had undergone chemo-/radiotherapy and patients with diabetes did not have higher complication rates. Conclusion DIEP flap surgery is an excellent option for autologous breast reconstruction, with a low rate of donor site morbidity and low complication rates. DIEP flap surgery carried out in a specialised interdisciplinary breast centre in a standardised clinical setting after prior careful patient selection to take account of risk factors such as high BMI and smoking is a reliable method with a low complication rate and satisfactory long-term reconstruction results.

Increasing evidence indicates that sialic acid plays an important role during nerve regeneration. Sialic acids can be modified in vitro as well as in vivo using metabolic oligosaccharide engineering of the N-acyl side chain. N-Propionylmannosamine (ManNProp) increases neurite outgrowth and accelerates the reestablishment of functional synapses in vitro. We investigated the influence of systemic ManNProp application using a specific in vivo mouse model. Using mice expressing axonal fluorescent proteins, we quantified the extension of regenerating axons, the number of regenerating axons, the number of arborising axons and the number of branches per axon 5 days after injury. Sciatic nerves from non-expressing mice were grafted into those expressing yellow fluorescent protein. We began a twice-daily intraperitoneal application of either peracetylated ManNProp (200 mg/kg) or saline solution 5 days before injury, and continued it until nerve harvest (5 days after transection). ManNProp significantly increased the mean distance of axonal regeneration (2.49 mm vs. 1.53 mm; P < 0.005) and the number of arborizing axons (21% vs. 16%; P = 0.008) 5 days after sciatic nerve grafting. ManNProp did not affect the number of regenerating axons or the number of branches per arborizing axon. The biochemical glycoengineering of the N-acyl side chain of sialic acid might be a promising approach for improving peripheral nerve regeneration.

Background Electrical stimulation immediately following nerve lesion helps regenerating axons cross the subsequently grafted nerve repair site. However, the results and the mechanisms remain open to debate. Some findings show that stimulation after crush injury increases axonal crossing of the repair site without affecting regeneration speed. Others show that stimulation after transection and fibrin glue repair doubles regeneration distance. Methods Using a sciatic-nerve-transection-graft in vivo model, we investigated the morphological behavior of regenerating axons around the repair site after unilateral nerve stimulation (20 Hz, 1 hour). With mice expressing axonal fluorescent proteins (thy1-YFP), we were able to calculate the following at 5 and 7 days: percentage of regenerating axons and arborizing axons, branches per axon, and regeneration distance and speed. Results Brief stimulation significantly increases the percentage of regenerating axons (5 days: 35.5 vs. 27.3% nonstimulated, p 0.05; 7 days: 43.3 vs. 33.9% nonstimulated, p 0.05), mainly by increasing arborizing axons (5 days: 49.3 [4.4] vs. 33.9 [4.1]% [p 0.001]; 7 days: 42.2 [5.6] vs. 33.2 [3.1]% [p 0.001]). Neither branches per arborizing axon nor regeneration speed were affected. Conclusion Our morphological data analysis revealed that electrical stimulation in this model increases axonal crossing of the repair site and promotes homogeneous perilesional branching, but does not affect regeneration speed.

The sciatic functional index (SFI) is a popular parameter for peripheral nerve evaluation that relies on footprints obtained with ink and paper. Drawbacks include smearing artefacts and a lack of dynamic information during measurement. Modern applications use digitized systems that can deliver results with less analytical effort and fewer mice. However, the systems are expensive (€40,000). This study aimed to evaluate the applicability and precision of a self-made, low-cost infrared system for evaluating SFI in mice. Mice were subjected to unilateral sciatic nerve crush injury (crush group; n = 7) and sham operation (sham group; n = 4). They were evaluated on the day before surgery, the 2(nd), 4(th) and 6(th) days after injury, and then every day up to the 23(rd) day after injury. We compared two SFI evaluation methods, i.e., conventional ink-and-paper SFI (C-SFI) and our infrared system (I-SFI). Our apparatus visualized footprints with totally internally reflected infrared light (950 nm) and a camera that can only detect this wavelength. Additionally we performed an analysis with the ladder beam walking test (LBWT) as a reference test. I-SFI assessment reduced the standard deviation by about 33 percent, from 11.6 to 7.8, and cut the variance around the baseline to 21 percent. The system thus requires fewer measurement repetitions and fewer animals, and cuts the cost of keeping the animals. The apparatus cost €321 to build. Our results show that the process of obtaining the SFI can be made more precise via digitization with a self-made, low-cost infrared system.

Background Systemic alteration of interleukin-6 (IL-6) influences peripheral nerve regeneration. We investigated the potential influences of in situ (at the coaptation site) IL-6 modulation in a peripheral-nerve-transection/sciatic-nerve-graft in vivo model. Methods We quantified the elongation of regenerating axons, the number of arborizing axons, and the number of branches per arborizing axon 7 days after the injury in mice expressing axonal fluorescent proteins (thy-1-YFP mice). Sciatic nerves from nonexpressing mice (C57Bl6 or IL-6 −/− mice) were grafted into those expressing yellow fluorescent protein. We altered the in situ IL-6 concentration by loading a topical gelatin sponge with an inhibiting IL-6 receptor antibody or IL-6 combined with a soluble IL-6 receptor. Sciatic nerves from IL-6 −/− mice were grafted into an additional group. The contralateral sham-operated side served as control in all the groups. Results Axonal elongation increased significantly with the in situ application of the IL-6 receptor antibody, while topical IL-6 significantly reduced the regeneration distance. The number of arborizing axons increased significantly in nerves grafted from IL-6 −/− mice, whereas branches per arborizing axons remained stable. Conclusion In situ IL-6 receptor inhibition and IL-6 −/− nerve grafting enhance early peripheral nerve regeneration in an acute murine injury model.

Background Breast cancer is the commonest form of cancer in women affecting almost a quarter of a million patients in the US annually. 30 percent of these patients and patients with genetic mutations undergo removal of the breast, as highlighted in a high profile celebrity patient. Although breast reconstruction with free microvascular transfer of a DIEAP flap from the abdomen is an ideal form of reconstruction, there have been misgivings about the complexity and potential complications. This study was aimed at clearing these misunderstandings and establishing the value of this form of breast reconstruction. Methods 1036 DIEAP flap breast reconstructions carried out at the University Hospital, Gent (five year period) and at the Sana Kliniken, Dusseldorf (three year period) were included prospectively. Comorbid factors like chemotherapy, radiotherapy, patient age >65 years, BMI >30 and smoking were recorded. Outcomes were evaluated over a mean follow up of 2 years. Results Overall complication rate related to the reconstructed breast and donor abdominal area was 6.8 percent. Total flap loss was seen in only 0.8 percent. The mean operating time was less than five hours. Older age, higher BMI, chemotherapy and radiotherapy did not have a significant influence on complication rates, however smoking resulted in significant delay in wound healing in the breast (p = 0.025) and abdominal wounds (p = 0.019). Conclusion The DIEAP flap is an excellent option for breast reconstruction, with a low level of donor site morbidity and complications. It is an autologous reconstruction that provides a stable long term result.

Currently, autologous breast reconstruction with a free tissue transfer from the lower abdomen is considered to be a safe method that provides a stable long-term solution. The DIEP-flap and the ms-2-TRAM-flap reconstructions have helped reduce donor site morbidity. In order to assess the potential differences between these techniques, we carried out myosonographic evaluations that assessed the muscle dynamics pre- and post-operatively. In addition to investigating the properties of the rectus abdominis muscle post-operatively, this prospective study also allowed us to analyse the muscle preoperatively and to investigate the prospects for harvesting a DIEP-flap as opposed to a TRAM-flap.Sixty patients underwent breast reconstruction with 71 (11 bilateral) free abdominal wall flaps (DIEP-: n = 48; ms-2-TRAM-flap: n = 23). Myosonographic examinations were performed preoperatively and at 3 and 6 months post-operatively. The thickness of the muscle at relaxation and maximum contraction and the difference between the muscle thickness measured at the two states were measured. A general-linear-model (GLM) was used for statistical analysis. The main variable was the surgical method, and the co-variables included BMI and patient age. The decision on whether to harvest a DIEP- or ms-2-TRAM-flap was made intra-operatively and based on the dominant perforator.It shows that the patients who underwent breast reconstruction with a DIEP-flap had significantly better muscle function (p 0.05) in the follow-up. In addition, the analysis revealed that better muscle function before surgery made it more likely that a patient would undergo a DIEP-flap-reconstruction successfully. Patient age also had a highly significant effect on muscle recovery (p 0.0005).This prospective study used a dynamic ultrasound evaluation of the abdominal wall and showed that the DIEP-flap significantly reduces donor site morbidity compared to the ms-2-TRAM-flap. The study also showed that good preoperative muscle function might increase the probability of surgeons performing a DIEP-flap reconstruction.

Summary Sternal wound infections after sternotomy are associated with high morbidity, high mortality and escalating treatment costs. Repeated radical debridement – with the removal of any hardware – and wound conditioning are the prerequisites for reconstruction. Muscle and, less frequently, omentum flaps are usually used for reconstruction. However, these flaps are associated with considerable donor-site morbidity, long operation times and aesthetic impairment. Fasciocutaneous flaps seem to be an alternative. This study presents our experience of using the second intercostal mammary artery fasciocutaneous perforator flap for defect closure in nine patients (mean age: 70.2 years). Following a retrospective chart review, we assessed data on patient demographics, the type of cardiac surgery, the prevalence of deep sternal wound infection (DSWI) risk factors, identified pathogens, surgery duration, hospitalization tim patients had undergone coronary artery bypass surgery, and two had valve replacements. The mean duration of surgery (121.4 ± 39 min) was short. The patients had a mean body mass index (BMI) of 32.8 ± 4.9 kg/m 2 . An average flap size of 124 ± 22 cm 2 sufficiently covered and obliterated each defect. One mediastinal haematoma required revision surgery. One wound dehiscence at the flap and two at the donor site were managed conservatively. Our experience reveals that a fasciocutaneous flap based on the second intercostal perforator of the internal mammary artery can be an alternative, quick-to-prepare flap for covering sternal defects. In adipose patients, it has sufficient bulk, and it is large enough to cover common sternal wounds. It also has low complication and morbidity rates, and it achieves an aesthetically pleasing result.

Microsurgical suturing is the gold standard of nerve coaptation. Although literature on the usefulness of fibrin glue as an alternative is becoming increasingly available, it remains contradictory. Furthermore, no data exist on how both repair methods might influence the morphological aspects (arborization; branching) of early peripheral nerve regeneration. We used the sciatic nerve transplantation model in thy-1 yellow fluorescent protein mice (YFP; n = 10). Pieces of nerve (1cm) were grafted from YFP-negative mice (n = 10) into those expressing YFP. We performed microsuture coaptations on one side and used fibrin glue for repair on the contralateral side. Seven days after grafting, the regeneration distance, the percentage of regenerating and arborizing axons, the number of branches per axon, the coaptation failure rate, the gap size at the repair site and the time needed for surgical repair were all investigated. Fibrin glue repair resulted in regenerating axons travelling further into the distal nerve. It also increased the percentage of arborizing axons. No coaptation failure was detected. Gap sizes were comparable in both groups. Fibrin glue significantly reduced surgical repair time. The increase in regeneration distance, even after the short period of time, is in line with the results of others that showed faster axonal regeneration after fibrin glue repair. The increase in arborizing axons could be another explanation for better functional and electrophysiological results after fibrin glue repair. Fibrin glue nerve coaptation seems to be a promising alternative to microsuture repair.

The key enzyme of sialic acid (Sia) biosynthesis is the bifunctional UDP-N-acetylglucosamine 2-epimerase/ManNAc kinase (GNE/MNK). It metabolizes the physiological precursor ManNAc and N-acyl modified analogues such as N-propionylmannosamine (ManNProp) to the respective modified sialic acid. Polysialic acid (polySia) is a crucial compound for several functions in the nervous system and is synthesized by the polysialyltransferases ST8SIA2 and ST8SIA4. PolySia can be modified in vitro and in vivo by metabolic glycoengineering of the N-acyl side chain of Sia. In vitro studies show that the application of ManNProp increases neurite outgrowth and accelerates the re-establishment of functional synapses. In this study, we investigate in vivo how ManNProp application might benefit peripheral nerve regeneration. In mice expressing axonal fluorescent proteins (thy-1-YFP), we transected the sciatic nerve and then replaced part of it with a sciatic nerve graft from non-expressing mice (wild-type mice or St8sia2 −/− mice). Analyses conducted 5 days after grafting showed that systemic application of ManNProp (200 mg/kg, twice a day, i.p.), but not of physiological ManNAc (1 g/kg, twice a day, i.p.), significantly increased the extent of axonal elongation, the number of arborizing axons and the number of branches per regenerating axon within the grafts from wild-type mice, but not in those from St8sia2 −/− mice. The results demonstrate that the application of ManNProp has beneficial effects on early peripheral nerve regeneration and indicate that the stimulation of axon growth depends on ST8SIA2 activity in the nerve graft.