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Neural Regeneration Research 2014年第22期9卷 1943-1948页

作者： Alba C.de Luca Stephanie P.Lacour Wassim Raffoul Pietro G.di Summa EPFL Centre for NeuroprostheticsLaboratory for Soft Bioelectronic InterfacesStation 171015 LausanneSwitzerland Department of Plastic Reconstructive and Hand SurgeryUniversity Hospital of Lausanne (CHUV)LausanneSwitzerland

peripheral nerve injury is a serious problem affecting signiifcantly patients’ life. Autografts are the“gold standard” used to repair the injury gap, however, only 50% of patients fully recover from the trauma. Artiifcial conduits are a valid alternative to repairing peripheral nerve. They aim at conifning the nerve environment throughout the regeneration process, and providing guidance to axon outgrowth. Biocompatible materials have been carefully designed to reduce inlfamma-tion and scar tissue formation, but modiifcations of the inner lumen are still required in order to optimise the scaffolds. Biomicking the native neural tissue with extracellular matrix ifllers or coatings showed great promises in repairing longer gaps and extending cell survival. In addition, extracellular matrix molecules provide a platform to further bind growth factors that can be released in the system over time. Alternatively, conduit ifllers can be used for cell transplantation at the injury site, reducing the lag time required for endogenous Schwann cells to proliferate and take part in the regeneration process. This review provides an overview on the importance of ex-tracellular matrix molecules in peripheral nerve repair.

关键词： peripheral nerve repair extracellular matrix nerve conduits surface modification fillers growth factors

Tissue-engineered constructs for peripheral nerve repair:current research concepts and future perspectives

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Plastic and Aesthetic Research 2015年第1期2卷 213-219页

作者： Alba C.de Luca Wassim Raffoul Francesco Giacalone Maddalena Bertolini Pietro G.di Summa EPFL Centre for NeuroprostheticsLaboratory for Soft Bioelectronic Interfaces1015 LausanneSwitzerland Department of Plastic Reconstructive and Hand SurgeryUniversity Hospital of Lausanne(Centre Hospitalier Universitaire Vaudois)1011 LausanneSwitzerland Department of Hand Surgery and Microsurgery CTO-Maria Adelaide Trauma Center10126 TorinoItaly

Traumatic injuries resulting in peripheral nerve lesions lead to important morbidity with devastating social and economic *** the lesioned nerve cannot be sutured directly,a nerve graft is generally required to bridge the *** autologous nerve grafting is still the first choice for reconstruction,it has the severe disadvantage of the sacrifice of a functional *** in tissue engineering and nerve regeneration may have a dramatic impact on clinical and surgical treatment of such nerve *** authors review the latest concepts in tissue engineering for nerve repair,including scaffold engineering of neural guides,biomaterial modification,cell therapy,growth factors delivery,and electrical *** literature is reviewed in detail,pointing out the most interesting present achievements and perspectives for future clinical *** search of the literature was performed using MEDLINE,Embase,and the Cochrane Library to identify research studies on peripheral nerve regeneration through tissue-engineered *** following medical subject headings were used to carry out a systematic search of the literature:“nerve regeneration”,“stem cells”,“biomaterial”,“extracellular matrix”,“functional regeneration”,“growth factors”and“microchannels”.Included literature was published between 1991 and *** reference lists from the retrieved articles were also reviewed for additional *** total,76 articles were included in this study.

关键词： Cell transplantation extracellular matrix growth factors nerve guidance conduit peripheral nerve repair surface modification

Use of nerve conduits for peripheral nerve injury repair:A Web of Science-based literature analysis

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Neural Regeneration Research 2012年第35期7卷 2826-2833页

作者： Jinniang Nan Xuguang Hu Hongxiu Li Xiaonong Zhang Renjing Piao Department of General Surgery Second People's Hospital of Panjin

OBJECTIVE： To identify global research trends in the use of nerve conduits for peripheral nerve injury repair. DATA RETRIEVAL： Numerous basic and clinical studies on nerve conduits for peripheral nerve injury repair were performed between 2002-2011. We performed a bibliometric analysis of the institutions, authors, and hot topics in the field, from the Web of Science, using the key words peripheral nerve and conduit or tube. SELECTION CRITERIA： Inclusion criteria： peer-reviewed published articles on nerve conduits for peripheral nerve injury repair, indexed in the Web of Science; original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. Exclusion criteria： articles requiring manual searching or telephone access; documents not published in the public domain; and several corrected papers. MAIN OUTCOME MEASURES：（a） Annual publication output; （b） publication type; （c） publication by research field; （d） publication by journal; （e） publication by funding agency; （f） publication by author; （g） publication by country and institution; （h） publications by institution in China; （i） most-cited papers. RESULTS： A total of 793 publications on the use of nerve conduits for peripheral nerve injury repair were retrieved from the Web of Science between 2002-2011. The number of publications gradually increased over the 10-year study period. Articles constituted the main type of publication. The most prolific journals were Biomaterials, Microsurge and Joumal of Biomedical Materials Research PartA. The National Natural Science Foundation of China supported 27 papers, more than any other funding agency. Of the 793 publications, almost half came from American and Chinese authors and institutions. CONCLUSION： nerve conduits have been studied extensively for peripheral nerve regeneration; however, many problems remain in this field, which are difficult for researchers to reach a consensus.

关键词： nerve conduit biomaterial axon neurotrophic factor stem cell extracellular matrix peripheralnerve injury peripheral nerve repair degradation biocompatibility neural regeneration

An update–tissue engineered nerve grafts for the repair of peripheral nerve injuries

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Neural Regeneration Research 2018年第5期13卷 764-774页

作者： Nitesh P.Patel Kristopher A.Lyon Jason H.Huang Texas A&M College of Medicine Temple TX USA Department of Neurosurgery Baylor Scott & White Healthcare Temple TX USA

peripheral nerve injuries（PNI） are caused by a range of etiologies and result in a broad spectrum of disability. While nerve autografts are the current gold standard for the reconstruction of extensive nerve damage, the limited supply of autologous nerve and complications associated with harvesting nerve from a second surgical site has driven groups from multiple disciplines, including biomedical engineering, neurosurgery, plastic surgery, and orthopedic surgery, to develop a suitable or superior alternative to autografting. Over the last couple of decades, various types of scaffolds, such as acellular nerve grafts（ANGs）, nerve guidance conduits, and non-nervous tissues, have been filled with Schwann cells, stem cells, and/or neurotrophic factors to develop tissue engineered nerve grafts（TENGs）. Although these have shown promising effects on peripheral nerve regeneration in experimental models, the autograft has remained the gold standard for large nerve gaps. This review provides a discussion of recent advances in the development of TENGs and their efficacy in experimental models. Specifically, TENGs have been enhanced via incorporation of genetically engineered cells, methods to improve stem cell survival and differentiation, optimized delivery of neurotrophic factors via drug delivery systems（DDS）, co-administration of platelet-rich plasma（PRP）, and pretreatment with chondroitinase ABC（Ch-ABC）. Other notable advancements include conduits that have been bioengineered to mimic native nerve structure via cell-derived extracellular matrix（ECM） deposition, and the development of transplantable living nervous tissue constructs from rat and human dorsal root ganglia（DRG） neurons. Grafts composed of non-nervous tissues, such as vein, artery, and muscle, will be briefly discussed.

关键词： peripheral nerve injury peripheral nerve repair tissue engineered nerve graft nerve conduit stem cells Schwann cells dorsal root ganglia neurons axon stretch-growth autologous tissue graft

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

peripheral nerve regeneration through nerve conduits evokes differential expression of growth-associated protein-43 in the spinal cord

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Neural Regeneration Research 2023年第8期18卷 1852-1856页

作者： Jesús Chato-Astrain Olga Roda David Sánchez-Porras Esther Miralles Miguel Alaminos Fernando Campos Óscar Darío García-García Víctor Carriel Department of Histology(Tissue Engineering Group) University of GranadaInstituto de Investigación Biosanitaria ibs.GRANADAGranadaSpain Department of Human Anatomy and Embryology University of GranadaGranadaSpain Unit of Clinical Neurophysiology University Hospital San CecilioGranadaSpain

Growth-associated protein 43 plays a key role in neurite outgrowth through cytoskeleton *** have previously demonstrated that structural damage of peripheral nerves induces growth-associated protein 43 upregulation to promote growth cone ***,the limited regenerative capacity of the central nervous system due to an inhibitory environment prevents major changes in neurite outgrowth and should be presumably associated with low levels of growth-associated protein 43 ***,central alterations due to peripheral nerve damage have never been assessed using the growthassociated protein 43 *** this study,we used the tubulization technique to repair 1 cm-long nerve gaps in the rat nerve injury/repair model and detected growth-associated protein 43 expression in the peripheral and central nervous ***,histological analysis of the regeneration process confirmed an active regeneration process of the nerve gaps through the conduit from 10 days *** growth-associated protein 43 expression profile varied across regions and follow-up times,from a localized expression to an abundant and consistent expression throughout the regeneration tissue,confirming the presence of an active nerve regeneration ***,spinal cord changes were also histologically assessed,and no apparent changes in the structural and cellular organization were observed using routine staining ***,remarkable differences and local changes appeared in growth-associated protein 43 expression at the spinal cord level,in particular at 20 days post-repair and ***-associated protein 43 protein was first localized in the gracile fasciculus and was homogeneously distributed in the left posterior *** findings differed from the growth-associated protein 43 pattern observed in the healthy control,which did not express growth-associated protein 43 at these *** results revealed a differential expression in growth-associate

关键词： growth-associated protein 43(GAP-43) immunohistochemistry nerve guide nerve tissue regeneration peripheral nerve repair spinal cord tissue engineering

peripheral nerve allograft:how innovation has changed surgical practice

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Plastic and Aesthetic Research 2022年第1期9卷 154-170页

作者： Gregory Buncke The Buncke Clinic San FranciscoCA 94114USA

The landscape of available technology and surgical technique has changed over the last several decades,thus leading to changes in the peripheral nerve repair surgical *** is a common procedure;however,it is well recognized that nerve repair should be performed tensionless,thus preventing the ability to perform direct repair with a nerve ***,nerve gaps were repaired with ***,autograft surgery has been associated with complications such as numbness and chronic pain,which left surgeons searching for *** allografts were first utilized in the 1800s but failed due to the immune *** the modern era,they were again utilized in the 1980s,but did not gain popularity because of the need for the use of *** was evident through the 1990s that continued innovation in peripheral nerve repair was needed,as studies showed that only approximately 50% of patients with nerve gap repair achieved good or excellent *** the 2000s,the advent of an engineered nerve allograft(Avance■nerve Graft)changed the landscape of peripheral nerve *** clinical evaluation of Avance showed that adequate sensation was able to be achieved in nerve gaps up to 30 mm,providing an alternative to *** engineered nerve allograft use became more conventional,studies showed 87.3% meaningful recovery in nerve gaps up to 50 ***,recent studies have shown that gaps between 50-70 mm have shown 69% meaningful *** technology and surgical technique continue to improve,these results are promising for large nerve gap repair.

关键词： peripheral nerve repair nerve autograft nerve allograft nerve conduit

Modification of tubular chitosan-based peripheral nerve implants: applications for simple or more complex approaches

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Neural Regeneration Research 2020年第8期15卷 1421-1431页

作者： Nina Dietzmeyer Maria F?rthmann Claudia Grothe Kirsten Haastert-Talini Institute of Neuroanatomy and Cell Biology Hannover Medical School Center for Systems Neuroscience (ZSN) Hannover

Surgical treatment of peripheral nerve injuries is still a major challenge in human *** to now,none of the well-developed microsurgical treatment options is able to guarantee a complete restoration of nerve *** restriction is also effective for novel clinically approved artificial nerve *** this review,we compare surgical repair techniques primarily for digital nerve injuries reported with relatively high prevalence to be valuable attempts in clinical digital nerve repair and point out their advantages and *** furthermore discuss the use of artificial nerve grafts with a focus on chitosan-based nerve guides,for which our own studies contributed to their approval for clinical *** the second part of this review,very recent future perspectives for the enhancement of tubular(commonly hollow)nerve guides are discussed in terms of their clinical translatability and ability to form three-dimensional constructs that biomimick the natural nerve *** includes materials that have already shown their beneficial potential in in vivo studies like fibrous intraluminal guidance structures,hydrogels,growth factors,and approaches of cell ***,we highlight upcoming future perspectives comprising co-application of stem cell *** our overview,we conclude that already simple attempts are highly effective to increase the regeneration supporting properties of nerve guides in experimental *** for bringing nerve repair with bioartificial nerve grafts to the next level,*** of defects>3 cm in human patients,more complex intraluminal guidance structures such as innovatively manufactured hydrogels and likely supplementation of stem cells or their secretome for therapeutic purposes may represent promising future perspectives.

关键词： bioartificial nerve graft biological nerve graft cell transplantation cellular products luminal structures peripheral nerve repair

Gene expression profiles of human adipose-derived mesenchymal stem cells dynamically seeded on clinically available processed nerve allografts and collagen nerve guides

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Neural Regeneration Research 2021年第8期16卷 1613-1621页

作者： Femke Mathot Nadia Rbia Roman Thaler Allan B.Dietz Andre Jvan Wijnen Allen T.Bishop Alexander Y.Shin Department of Orthopedic Surgery Mayo ClinicRochesterMNUSA Department of Plastic Surgery RadboudumcNijmegenThe Netherlands Department of Dermatology Erasmus Medical CenterRotterdamThe Netherlands Department of Biochemistry and Molecular Biology Mayo ClinicRochesterMNUSA Department of Laboratory Medicine and Pathology Mayo ClinicRochesterMNUSA

It was hypothesized that mesenchymal stem cells(MSCs) could provide necessary trophic factors when seeded onto the surfaces of commonly used nerve graft substitutes. We aimed to determine the gene expression of MSCs when influenced by Avance■ nerve Grafts or Neura Gen■ nerve Guides. Human adipose-derived MSCs were cultured and dynamically seeded onto 30 Avance■ nerve Grafts and 30 Neura Gen■ nerve Guides for 12 hours. At six time points after seeding, quantitative polymerase chain reaction analyses were performed for five samples per group. Neurotrophic [nerve growth factor(NGF), glial cell line-derived neurotrophic factor(GDNF), pleiotrophin(PTN), growth associated protein 43(GAP43) and brain-derived neurotrophic factor(BDNF)], myelination [peripheral myelin protein 22(PMP22) and myelin protein zero(MPZ)], angiogenic [platelet endothelial cell adhesion molecule 1(PECAM1/CD31) and vascular endothelial cell growth factor alpha(VEGFA)], extracellular matrix(ECM) [collagen type alpha I(COL1A1), collagen type alpha III(COL3A1), Fibulin 1(FBLN1) and laminin subunit beta 2(LAMB2)] and cell surface marker cluster of differentiation 96(CD96) gene expression was quantified. Unseeded Avance■ nerve Grafts and Neura Gen■ nerve Guides were used to evaluate the baseline gene expression, and unseeded MSCs provided the baseline gene expression of MSCs. The interaction of MSCs with the Avance■ nerve Grafts led to a short-term upregulation of neurotrophic(NGF, GDNF and BDNF), myelination(PMP22 and MPZ) and angiogenic genes(CD31 and VEGFA) and a long-term upregulation of BDNF, VEGFA and COL1A1. The interaction between MSCs and the Neura Gen■ nerve Guide led to short term upregulation of neurotrophic(NGF, GDNF and BDNF) myelination(PMP22 and MPZ), angiogenic(CD31 and VEGFA), ECM(COL1A1) and cell surface(CD96) genes and long-term upregulation of neurotrophic(GDNF and BDNF), angiogenic(CD31 and VEGFA), ECM genes(COL1A1, COL3A1, and FBLN1) and cell surface(CD96) genes. Analysis demonstrat

关键词： Avance■nerve Grafts dynamic seeding mesenchymal stem cell NeuraGen■nerve Guides peripheral nerve repair qPCR

Scaffoldless tissue-engineered nerve conduit promotes peripheral nerve regeneration and functional recovery after tibial nerve injury in rats

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Neural Regeneration Research 2017年第9期12卷 1529-1537页

作者： Aaron M.Adams Keith W.VanDusen Tatiana Y.Kostrominova Jacob P.Mertens Lisa M.Larkin Department of Molecular and Integrated Physiology University of Michigan Department of Anatomy and Cell Biology Indiana University School of Medicine Department of Biomedical Engineering University of Michigan

Damage to peripheral nerve tissue may cause loss of function in both the nerve and the targeted muscles it innervates. This study compared the repair capability of engineered nerve conduit （ENC）, engineered fibroblast conduit （EFC）, and autograft in a 10-mm tibial nerve gap. ENCs were fabricated utilizing primary fibroblasts and the nerve cells of rats on embryonic day 15 （E 15）. EFCs were fabricated utilizing primary fi- broblasts only. Following a 12-week recovery, nerve repair was assessed by measuring contractile properties in the medial gastrocnemius muscle, distal motor nerve conduction velocity in the lateral gastrocnemius, and histology of muscle and nerve. The autografts, ENCs and EFCs reestablished 96%, 87% and 84% of native distal motor nerve conduction velocity in the lateral gastrocnemius, 100%, 44% and 44% of native specific force of medical gastrocnemius, and 63%, 61% and 67% of native medial gastrocnemius mass, re- spectively. Histology of the repaired nerve revealed large axons in the autograft, larger but fewer axons in the ENC repair, and many smaller axons in the EFC repair. Muscle histology revealed similar muscle fiber cross-sectional areas among autograft, ENC and EFC repairs. In conclusion, both ENCs and EFCs promot- ed nerve regeneration in a 10-mm tibial nerve gap repair, suggesting that the El5 rat nerve cells may not be necessary for nerve regeneration, and EFC alone can suffice for peripheral nerve injury repair.

关键词： nerve regeneration peripheral nerve repair neural conduit tissue engineering fibroblasts neuralcells