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Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

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Neural Regeneration research 2025年第6期20卷 1789-1800页

作者： Carina Hromada Patrick Heimel Markus Kerbl LászlóGál Sylvia Nürnberger Barbara Schaedl James Ferguson Nicole Swiadek Xavier Monforte Johannes C.Heinzel Antal Nógrádi Andreas H.Teuschl-Woller David Hercher department Life Science Engineering University of Applied Sciences Technikum WienViennaAustria Austrian Cluster for Tissue Regeneration ViennaAustria Ludwig Boltzmann Institute for Traumatology The Research Center in Cooperation with AUVAViennaAustria University Clinic of Dentistry Medical University of ViennaViennaAustria department of plastic Reconstructive and Aesthetic SurgeryLandesklinikum Wiener Neustadt2700 Wiener NeustadtAustria department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Medical University of Vienna Department of Orthopedics and Trauma SurgeryDevision of Trauma SurgeryViennaAustria department of Hand- PlasticReconstructive and Burn SurgeryBG Unfallklinik TuebingenUniversity of TuebingenTuebingenGermany

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimizatio

关键词： axon regeneration blood vessel functional recovery macroporous nerve lesion peripheral nerve repair sciatic nerve silk-based nerve guidance conduit vascularization

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End-to-end and end-to-side neurorrhaphy between thick donor nerves and thin recipient nerves:an axon regeneration study in a rat model

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Neural Regeneration research 2018年第4期13卷 699-703页

作者： Tohru Tateshita Kazuki Ueda Akiyoshi Kajikawa department of plastic and reconstructive surgery St.Marianna Medical University department of plastic and reconstructive surgery Fukushima Medical University

During nerve reconstruction,nerves of different thicknesses are often sutured together using end-to-side neurorrhaphy and end-to-end neurorrhaphy *** this study,the effect of the type of neurorrhaphy on the number and diameter of regenerated axon fibers was studied in a rat facial nerve repair *** inflow-type end-to-side and end-to-end neurorrhaphy model with nerve stumps of different thicknesses（2：1 diameter ratio） was created in the facial nerve of 14 adult male Sprague-Dawley *** 6 and 12 weeks,nerve regeneration was evaluated in the rats using the following outcomes：total number of myelinated axons,average minor axis diameter of the myelinated axons in the central and peripheral sections,and axon regeneration ***-to-end neurorrhaphy resulted in a significantly greater number of regenerated myelinated axons and rate of regeneration after 6 weeks than end-to-side neurorrhaphy;however,no such differences were observed at 12 *** the regenerated axons were thicker at 12 weeks than at 6 weeks,no significant differences in axon fiber thickness were detected between end-to-end and end-toside ***,end-to-end neurorrhaphy resulted in greater numbers of regenerated axons and increased axon regeneration rate during the early postoperative *** rapid reinnervation is one of the most important factors influencing the restoration of target muscle function,we conclude that end-to-end neurorrhaphy is desirable when suturing thick nerves to thin nerves.

关键词： epineural window transplantation nerve reconstruction suturing facial nerve repair axonal repair neurosurgery peripheral nerve neural regeneration

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Delayed peripheral nerve repair: methods, including surgical ‘cross-bridging' to promote nerve regeneration

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Neural Regeneration research 2015年第10期10卷 1540-1544页

作者： Tessa Gordon Placheta Eva Gregory H.Borschel department of surgery Division of Plastic Reconstructive Surgery the Hospital for Sick Children

Despite the capacity of Schwann cells to support peripheral nerve regeneration, functional recovery after nerve injuries is frequently poor, especially for proximal injuries that require regenerating axons to grow over long distances to reinnervate distal targets. Nerve transfers, where small fascicles from an adjacent intact nerve are coapted to the nerve stump of a nearby denervated muscle, allow for functional return but at the expense of reduced numbers of innervating nerves. A 1-hour period of 20 Hz electrical nerve stimulation via electrodes proximal to an injury site accelerates axon outgrowth to hasten target reinnervation in rats and humans, even after delayed surgery. A novel strategy of enticing donor axons from an otherwise intact nerve to grow through small nerve grafts（cross-bridges） into a denervated nerve stump, promotes improved axon regeneration after delayed nerve repair. The efficacy of this technique has been demonstrated in a rat model and is now in clinical use in patients undergoing cross-face nerve grafting for facial paralysis. In conclusion, brief electrical stimulation, combined with the surgical technique of promoting the regeneration of some donor axons to ‘protect＇ chronically denervated Schwa nn cells, improves nerve regeneration and, in turn, functional outcomes in the management of peripheral nerve injuries.

关键词： peripheral nerve injury nerve repair nerve regeneration Schwann cells electrical nerve stimulation axon regeneration

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New autologous material for the frontalis suspension technique:superficial temporal fascia

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International Journal of Ophthalmology(English edition) 2016年第2期9卷 315-317页

作者： Elif Sari Hulda Rifat Ozakpinar Ali Teoman Tellioglu department of plastic Reconstructive and Aesthetic Surgery Kirikkale University Faculty of Medicine Clinic of plastic Reconstructive and Aesthetic SurgeryDiskapi Yildirim Beyazit Education and Research Hospital department of plastic Reconstructive and Aesthetic Surgery Yildirim Beyazit University Faculty of Medicine

The frontalis suspension technique, which is a well-known surgical procedure, has been used for congenital ptosis for many years [1]. Several autologous and foreign grafts or materials have been preferred for this suspension, such as collagen, tensor fascia lata, palmaris longus tendon, deep temporal fascia, catgut, prolene, silicone, stainless steel, and supramid suture . Each of these have their own advantages and disadvantages; however, the superficial temporal fascia has not been used for the frontalis suspension method before.

关键词： Figure New autologous material for the frontalis suspension technique

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A self-made, low-cost infrared system for evaluating the sciatic functional index in mice

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Neural Regeneration research 2016年第5期11卷 829-834页

作者： Lukas Fricker Vincenzo Penna Florian Lampert G.Bjoern Stark Christian Witzel Georgios Koulaxouzidis department of plastic and Hand surgery University of Freiburg Medical Center plastic and reconstructive surgery Charité – Universit?tsmedizin Berlin

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 2nd, 4th and 6th days after injury, and then every day up to the 23rd day after injury. We compared two SFI evaluation methods, i.e., conventional inkand-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.

关键词： nerve regeneration sciatic nerve crush frustrated total internal reflection infrared ladder beamwalking test error rate mouse peripheral nerve injury neural regeneration

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Perforator-based flaps for the treatment of burn scar contractures: a review

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Burns & Trauma 2017年第1期5卷 9-16页

作者： C.M.Stekelenburg R.E.Marck P.D.H.M.Verhaegen K.W.Marck P.P.M.van Zuijlen Burn Center and department of plastic Reconstructiveand Hand SurgeryRed Cross HospitalVondellaan 131942 LE BeverwijkThe Netherlands department of plastic Reconstructiveand Hand SurgeryUniversity Medical CenterUtrechtThe Netherlands department of plastic Reconstructiveand Hand SurgeryAcademical Medical CenterAmsterdamThe Netherlands department of plastic Reconstructiveand Hand SurgeryMOVE Research InstituteVU University Medical CenterAmsterdamThe Netherlands department of plastic Reconstructiveand Hand SurgeryIsalaZwolleThe Netherlands department of plastic surgery Medisch Centrum LeeuwardenLeeuwardenThe Netherlands.

Patients with burn scars often experience functional problems because of scar contractures. Surgical treatment may be indicated for those burn scar contractures. If the contractures are small and linear, the contraction bands can be treated with local transposition flaps like the Z-plasty. Broader, diffuse contractures are more challenging and require a different surgical approach, such as the use of local tissue. The use of perforator-based flaps is promising;however, their true clinical significance for this type of burn reconstructions still needs to be determined. Therefore, we performed a review to evaluate the role of perforator-based flaps for burn scar contracture treatment. Electronic databases were searched using a predefined search strategy. Studies evaluating the long-term outcome of perforator-based flaps for the treatment of burn scar contractures were included. The methodological quality was tested and data was summarized. Five hundred and ten papers were identified of which eleven met the inclusion criteria. One study was a randomized controlled trial;ten were cohort studies of a pre-postoperative design. The papers described outcomes of free flaps and local flaps. Most studies had methodological shortcomings and used inappropriate statistical methods. Perforator-based interposition flaps appear to be highly relevant for burn scar contracture treatment. However, due to the paucity and low quality of the studies that were assessed, no definitive conclusions about the true clinical significance could be reached. And therefore, only recommendations could be given for improvement of the quality of further primary research on the effectiveness of perforator-based flaps for burn scar contracture release.

关键词： Burn Scar Contracture Perforator flap

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Fibrin glue repair leads to enhanced axonal elongation during early peripheral nerve regeneration in an in vivo mouse model

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Neural Regeneration research 2015年第7期10卷 1166-1171页

作者： Georgios Koulaxouzidis Gernot Reim Christian Witzel department of plastic and Hand surgery University of Freiburg Medical Centre plastic and reconstructive surgery – Interdisciplinary Breast Center Charité–Universit?tsmedizin Berlin

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.

关键词： nerve regeneration fibrin glue peripheral nerve regeneration thy-1-YFP mice sciatic nerve branching arborisation neural regeneration

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Promoting axonal regeneration following nerve surgery： a perspective on ultrasound treatment for nerve injuries

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Neural Regeneration research 2018年第9期13卷 1530-1533页

作者： Konstantin D. Bergmeister Simeon C. Daeschler Patrick Rhodius Philipp Schoenle Arne Bocker Ulrich Kneser Leila Harhaus department of Hand Plastic and Reconstructive Surgery Burn Center Department of Plastic and Hand Surgery University of Heidelberg BG Trauma Hospital Ludwigshafen Ludwigshafen Germany

Nerve injury is often associated with limited axonal regeneration and thus leads to delayed or incomplete axonal *** a consequence of slow nerve regeneration,target muscle function is often insufficient and leads to a lifelong ***,the diagnosis of nerve injuries has been improved and likewise surgical reconstruction has undergone significant ***,the problem of slow nerve regeneration has not been *** a recent meta-analysis,we have shown that the application of low-intensity ultrasound promotes nerve regeneration experimentally and thereby can improve functional *** we want to demonstrate the experimental effect of low intensity ultrasound on nerve regeneration,the current state of investigations and its possible future clinical applications.

关键词： peripheral nerve injuries nerve regeneration reinnervation experimental studies low-intensityultrasound adjunct treatment nerve reconstruction nerve surgery axonal injury

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Influence of immobilization and sensory re-education on the sensory recovery after reconstruction of digital nerves with direct suture or muscle-in-vein conduits

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Neural Regeneration research 2016年第2期11卷 338-344页

作者： Theodora Manoli Jennifer Lynn Schiefer Lukas Schulz Thomas Fuchsberger Hans-Eberhard Schaller department of Hand Plastic and Reconstructive Surgery Burn Unit BG Trauma Center University of Tuebingen

The influence of duration of immobilization and postoperative sensory re-education on the final outcome after reconstruction of digital nerves with direct suture or muscle-in-vein conduits was investigated. The final sensory outcome of 35 patients with 41 digital nerve injuries, who either underwent a direct suture（DS） or a nerve reconstruction with muscle-in-vein conduits（MVC）, was assessed the earliest 12 months postoperatively using static and moving two-point discrimination as well as Semmes-Weinstein monofilaments. There was no significant difference in sensory recovery in cases with an immobilization of 3–7 days versus 10 days in the DS or MVC group. Moreover, no statistically significant difference in sensory recovery was found in cases receiving postoperative sensory re-education versus those not receiving in the DS or MVC group. An early mobilization does not seem to have a negative impact on the final outcome after digital nerve reconstruction. The effect of sensory re-education after digital nerve reconstruction should be reconsidered.

关键词： nerve regeneration peripheral nerve digital nerve sensory re-education immobilization digital direct suture muscle-in-vein conduits

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Sutureless vascular anastomotic approaches and their potential impacts

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Bioactive Materials 2024年第8期38卷 73-94页

作者： Joseph G.Ribaudo Kevin He Sarah Madira Emma R.Young Cameron Martin Tingying Lu Justin M.Sacks Xiaowei Li Division of plastic and reconstructive surgery Department of SurgeryWashington University in St.LouisMO63110USA department of plastic surgery Johns Hopkins School of MedicineBaltimoreMD21287USA

Sutureless anastomotic devices present several advantages over traditional suture anastomosis,including expanded global access to microvascular surgery,shorter operation and ischemic times,and reduced ***,their adaptation for arterial use remains a *** review aims to provide a comprehensive overview of sutureless anastomotic approaches that are either FDA-approved or under *** approaches include extraluminal couplers,intraluminal devices,and methods assisted by lasers or vacuums,with a particular emphasis on tissue *** analyze these devices for artery compatibility,material composition,potential for intimal damage,risks of thrombosis and restenosis,and complications arising from their deployment and ***,we discuss the challenges faced in the development and clinical application of sutureless anastomotic ***,a sutureless anastomotic device or technique should eliminate the need for vessel eversion,mitigate thrombosis through either biodegradation or the release of antithrombotic drugs,and be easily deployable for broad *** transformative potential of sutureless anastomotic approaches in microvascular surgery highlights the necessity for ongoing innovation to expand their applications and maximize their benefits.

关键词： Vascular Anastomotic device Tissue adhesive Patency OUTLINE

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