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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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A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

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Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon C.Daeschler Katelyn J.W.So Konstantin Feinberg Marina Manoraj Jenny Cheung Jennifer Zhang Kaveh Mirmoeini JPaul Santerre Tessa Gordon Gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA division of plastic and reconstructive surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

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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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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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Contemporary approach to soft-tissue reconstruction of the lower extremity after trauma

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Burns & Trauma 2021年第1期9卷 351-363页

作者： Matthew R.Zeiderman Lee L.Q.Pu division of plastic&reconstructive surgery Department of SurgeryUniversity of CaliforniaDavisSacramentoCAUSA

The complex lower extremity wound is frequently encountered by orthopedic and plastic *** in wound care,soft tissue coverage and surgical fixation techniques allow for improved functional outcomes in this patient population with highly morbid *** this review,the principles of reconstruction of complex lower extremity traumatic wounds are *** principles include appropriate initial evaluation of the patient and mangled extremity,as well as appropriate patient selection for limb *** authors emphasize proper planning for reconstruction,timing of reconstruction and the importance of an understanding of the most appropriate reconstructive *** role of different reconstructive and wound care modalities is discussed,notably negative pressure wound therapy and dermal *** role of pedicled flaps and microvascular free-tissue transfer are discussed,as are innovations in understanding of perforator anatomy and perforator flap surgery that have broadened the reconstruction surgeon’s ***,the importance of a multidisciplinary team is highlighted via the principle of the orthoplastic approach to management of complex lower extremity *** completion of this review,the reader should have a thorough understanding of the principles of contemporary lower extremity reconstruction.

关键词： Lower extremity Soft tissue Reconstruction Trauma Surgical approach

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Surgical solutions to the problem of massive weight loss

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World Journal of Gastroenterology 2006年第41期12卷 6602-6607页

作者： Jason A Spector Steven M Levine Nolan S Karp division of plastic surgery Weill Medicine College of Cornell University New YorkNY 10021United States Institute of reconstructive and plastic surgery Division of Plastic SurgeryNew York University School of MedicineNew YorkNY 10016United States

In response to the global rise in obesity, bariatric surgery has become increasingly more popular and successful As a result, the demand for body contouring following massive weight loss is rapidly growing. Although bariatric procedures may produce impressive weight loss, people who achieve massive weight loss are often unhappy with the hanging folds of skin and subcutaneous tissue that remain. This review examines the nature of the post-bariatric deformity in each body region and briefly reviews common approaches to their treatment.

关键词： Weight loss Bariatric surgery Body contour surgery

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Does crossover innervation really affect the clinical outcome？ A comparison of outcome between unilateral and bilateral digital nerve repair

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Neural Regeneration Research 2016年第9期11卷 1499-1505页

作者： Melike Oruc Kadri Ozer Ozlem Colak Yüksel Kankaya Ugur Kocer Ankara Training and Research Hospital Plastic Reconstructive and Aesthetic Surgery Clinic Ankara Turkey Aydin State Hospital Plastic Reconstructive and Aesthetic Surgery Clinic Aydin Turkey Istanbul Okmeydani Training and Research Hospital Plastic Reconstructive and Aesthetic Surgery Clinic Istanbul Turkey

Digital nerve injuries are the mostly detected nerve injury in the upper extremity. However, since the clinical phenomenon of crossover innervation at some degree from uninjured digital nerve to the in- jured side occurs after digital nerve injuries is sustained, one could argue that this concept might even result in the overestimation of the outcome of the digital nerve repair. With this knowledge in mind, this study aimed to present novel, pure, focused and valuable clinical data by comparing the outcomes of bilateral and unilateral digital nerve repair. A retrospective review of 28 fingers with unilateral or bilateral digital nerve repair using end-to-end technique in 19 patients within 2 years was performed. Weber＇s two-point discrimination, sharp/dull discrimination, warm/cold sensation and Visual Analog Scale scoring were measured at final 12-month follow ups in all patients. There was no significant difference in recovery of sensibility after unilateral and bilateral digital nerve repairs. Though there is crossover innervation microscopically, it is not important in the clinical evaluation period. According to clinical findings from this study, crossover innervations appear to be negligible in the estimation of outcomes of digital neurorrhaphy.

关键词： nerve regeneration digital nerve repair unilateral bilateral crossover innervation sensibility neurorrhaphy nerve sprouting neural regeneration

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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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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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Lower extremity nerve transfers:an underappreciated reconstructive approach

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plastic and Aesthetic Research 2023年第1期10卷 475-484页

作者： Jenny L.Yu Christopher S.Crowe Angelo B.Lipira Ravi F.Sood division of plastic and reconstructive surgery Department of SurgeryUniversity of WashingtonSeattleWA 98195USA division of plastic and reconstructive surgery Department of SurgeryOregon Health&Science UniversityPortlandOR 97239USA division of plastic and reconstructive surgery Department of SurgeryUniversity of California DavisSacramentoCA 95817USA

Lower extremity peripheral nerve injuries can be highly morbid to patients and challenging problems for reconstructive surgeons to *** transfers have recently emerged as a promising technique in the treatment of these *** nerve-transfer paradigm is predicated on the use of an expendable,unaffected nerve as a donor of axons to restore motor or sensory function in the target end *** transfers close to the end motor or sensory organ may allow for earlier and more robust reinnervation compared to more proximal primary repair or ***,as clinical data on outcomes and rigorous comparative studies remain scarce,reconstructive surgeons must rely on principle-based treatment including a detailed understanding of lower extremity neuromuscular anatomy,gait mechanics,and nerve physiology to develop an appropriate treatment plan for each patient with the goal of functional limb restoration and independent *** this article,we review current concepts of lower extremity nerve transfers,including techniques and outcomes according to indication.

关键词： Lower extremity nerve injury nerve transfer peripheral nerve surgery

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