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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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PI3K/AKT signaling and neuroprotection in ischemic stroke:molecular mechanisms and therapeutic perspectives

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Neural Regeneration Research 2025年第10期20卷 2758-2775页

作者： Tianlong Liu Xiaolin Li Xiaowei Zhou Wei Chen Aidong Wen Minna Liu Yi Ding department of Pharmacy Xijing HospitalFourth Military Medical UniversityXi’anShaanxi ProvinceChina department of Pharmacy The 940 Hospital of Joint Logistics Support Forces of Chinese PLALanzhouGansu ProvinceChina department of Pharmacy The 944 Hospital of Joint Logistics Support Forces of Chinese PLAJiuquanGansu ProvinceChina department of Nephrology The 940 Hospital of Joint Logistics Support Forces of Chinese PLALanzhouGansu ProvinceChina

It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic *** a result,the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from *** article reviews the pathological mechanisms and advancements in research related to the signaling pathways in ischemic stroke,with a focus on the PI3K/AKT signaling *** key findings include the following:(1)The complex pathological mechanisms of ischemic stroke can be categorized into five major types:excitatory amino acid toxicity,Ca^(2+)overload,inflammatory response,oxidative stress,and apoptosis.(2)The PI3K/AKT-mediated signaling pathway is closely associated with the occurrence and progression of ischemic stroke,which primarily involves the NF-κB,NRF2,BCL-2,mTOR,and endothelial NOS signaling pathways.(3)Natural products,including flavonoids,quinones,alkaloids,phenylpropanoids,phenols,terpenoids,and iridoids,show great potential as candidate substances for the development of innovative anti-stroke medications.(4)Recently,novel therapeutic techniques,such as electroacupuncture and mesenchymal stem cell therapy,have demonstrated the potential to improve stroke outcomes by activating the PI3K/AKT signaling pathway,providing new possibilities for the treatment and rehabilitation of patients with ischemic *** investigations should focus on the direct regulatory mechanisms of drugs targeting the PI3K/AKT signaling pathway and their clinical translation to develop innovative treatment strategies for ischemic stroke.

关键词： apoptosis autophagy inflammation ischemic stroke neuroprotection oxidative stress pathogenesis phosphatidylinositol 3-kinase protein kinase B therapeutics

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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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Tranylcypromine upregulates Sestrin 2 expression to ameliorate NLRP3-related noise-induced hearing loss

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Neural Regeneration Research 2025年第5期20卷 1483-1494页

作者： Xihang Chen Zhifeng Chen Menghua Li Weiwei Guo Shuolong Yuan Liangwei Xu Chang Lin Xi Shi Wei Chen Shiming Yang Senior department of Otolaryngology Head and Neck surgery Chinese PLA General HospitalChinese PLA Medical SchoolBeijingChina State Key Laboratory of Hearing and Balance Science BeijingChina National Clinical Research Center for Otolaryngologic Diseases BeijingChina Key Laboratory of Hearing Science Ministry of EducationBeijingChina Beijing Key Laboratory of Hearing Impairment Prevention and Treatment BeijingChina department of Otorhinolaryngology Head and Neck surgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina department of Otolaryngology Head and Neck surgery The 940th Hospital of Joint Logistics Support Force of Chinese PLALanzhouGansu ProvinceChina Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikouHainan ProvinceChina Academician Workstation of Hainan University School of Pharmaceutical SciencesYazhou BaySanyaHainan ProvinceChina

Noise-induced hearing loss is the primary non-genetic factor contributing to auditory ***,there are currently no effective pharmacological interventions for patients with noise-induced hearing ***,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory *** established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 *** found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with *** noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with *** findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell ***,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy *** treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)*** conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing *** findings suggest that inhibiting lysine-specific demethylase 1 is a

关键词： 4-hydroxynonenal apoptosis autophagy cleaved caspase-3 inflammation NOD-like receptor family pyrin domain-containing 3(NLRP3) noise-induced hearing loss oxidative stress Sestrin2 tranylcypromine

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Brachioradialis tendon transfer and palmaris longus tendon graft for thumb avulsion:A case report and review of literature

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World Journal of Clinical Cases 2025年第4期13卷 48-55页

作者： Pierre Curings Sonia Ramos-Pascual Kinga Michalewska Nicolas Gibert Lionel Erhard Mo Saffarini AlexisNogier department of Hand surgery Clinique TrenelSainte-Colombe 69560France Medical Research ReSurg SANyon 1260VaudSwitzerland department of Hand surgery Hand and Upper Limb Surgical InstituteVilleurbanne 69100France department of Orthopaedics Clinique TrenelSainte-Colombe 69560France

BACKGROUND Thumb replantation following complete traumatic avulsion requires complex techniques to restore function,especially in cases of avulsion at the level of the metacarpophalangeal joint(MCP I)and avulsion of the flexor pollicis longus(FPL)at the musculotendinous *** treatments include direct tendon suture or tendon transfer,most commonly from the ring *** optimize function and avoid donor finger complications,we performed thumb replantation with flexion restoration using brachioradialis(BR)tendon transfer with palmaris longus(PL)tendon *** SUMMARY A 20-year-old left-handed male was admitted for a complete traumatic left thumb amputation following an accident while sliding from the top of a *** patient presented with skin and bone avulsion at the MCP I,avulsion of the FPL tendon at the musculotendinous junction(zone 5),avulsion of the extensor pollicis longus tendon(zone T3),and avulsion of the thumb’s collateral arteries and *** patient was treated with two stage thumb *** first intervention consisted of thumb replantation with MCP I arthrodesis,resection of avulsed FPL tendon and implantation of a silicone tendon *** second intervention consisted of PL tendon graft and BR tendon ***-up at 10 months showed good outcomes with active interphalangeal flexion of 70°,grip strength of 45 kg,key pinch strength of 15 kg and two-point discrimination threshold of 4 *** Flexion restoration after complete thumb amputation with FPL avulsion at the musculotendinous junction can be achieved using BR tendon transfer with PL tendon graft.

关键词： Brachioradialis tendon transfer Flexor pollicis longus Palmaris longus tendon graft Replantation Thumb amputation Thumb avulsion Case report

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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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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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Dynamic culture of a thermosensitive collagen hydrogel as an extracellular matrix improves the construction of tissue-engineered peripheral nerve

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Neural Regeneration Research 2014年第14期9卷 1371-1378页

作者： Lanfeng Huang Rui Li Wanguo Liu Jin Dai Zhenwu Du Xiaonan Wang Jianchao Ma Jinsong Zhao department of joint surgery Orthopedics Hospital of the Second Hospital of Jilin University Centre of Hand & Foot surgery and Reparative & reconstructive surgery Orthopedics Hospital of the Second Hospital of Jilin University department of Orthopedics surgery the Third Hospital of Jilin University Institute of Orthopedics the Second Hospital of Jilin University department of Ophthalmology the Second Hospital of Jilin University

Tissue engineering technologies offer new treatment strategies for the repair of peripheral nerve injury, hut cell loss between seeding and adhesion to the scaffold remains inevitable. A thermosensitive collagen hydrogel was used as an extracellular matrix in this study and combined with bone marrow mesenchymal stem cells to construct tissue-engineered peripheral nerve composites in vitro. Dynamic culture was performed at an oscillating frequency of 0.5 Hz and 35° swing angle above and below the horizontal plane. The results demonstrated that bone marrow mesenchymal stem cells formed membrane-like structures around the poly-L-lactic acid scaffolds and exhibited regular alignment on the composite surface. Collagen was used to fill in the pores, and seeded cells adhered onto the poly-L-lactic acid fibers. The DNA content of the bone marrow mesenchymal stem cells was higher in the composites constructed with a thermosensitive collagen hydrogel compared with that in collagen I scaffold controls. The cellular DNA content was also higher in the thermosensitive collagen hydrogel composites constructed with the thermosensitive collagen hydrogel in dynamic culture than that in static culture. These results indicate that tissue-engineered composites formed with thermosensitive collagen hydrogel in dynamic culture can maintain larger numbers of seeded cells by avoiding cell loss during the initial adhe-sion stage. Moreover, seeded cells were distributed throughout the material.

关键词： nerve regeneration peripheral nerve biomaterials extracellular matrix tissueengineering nerve scaffold bone marrow mesenchymal stem cells thermosensitive collagen hydrogel poly-L-lactic acid dynamic culture NSFC grant neural regeneration

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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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