Peripheral Nerve Tissue Engineering Research Articles

Advanced Functional Materials Solutions to Engineering the Neural Interface

Advanced Functional Materials Solutions to Engineering the Neural Interface

An allogeneic \u2018off the shelf\u2019 therapeutic strategy for peripheral nerve tissue engineering using clinical grade human neural stem cells

Artificial tissues constructed from therapeutic cells offer a promising approach for improving the treatment of severe peripheral nerve injuries. In this study the effectiveness of using CTX0E03, a conditionally immortalised human neural stem cell line, as a source of allogeneic cells for constructing living artificial nerve repair tissue was tested. CTX0E03 cells were differentiated then combined with collagen to form engineered neural tissue (EngNT-CTX), stable aligned sheets of cellular hydrogel. EngNT-CTX sheets were delivered within collagen tubes to repair a 12 mm sciatic nerve injury model in athymic nude rats. Autologous nerve grafts (autografts) and empty tubes were used for comparison. After 8 weeks functional repair was assessed using electrophysiology. Further, detailed histological and electron microscopic analysis of the repaired nerves was performed. Results indicated that EngNT-CTX supported growth of neurites and vasculature through the injury site and facilitated reinnervation of the target muscle. These findings indicate for the first time that a clinically validated allogeneic neural stem cell line can be used to construct EngNT. This provides a potential ‘off the shelf’ tissue engineering solution for the treatment of nerve injury, overcoming the limitations associated with nerve autografts or the reliance on autologous cells for populating repair constructs.

3D Manufacture of Gold Nanocomposite Channels Facilitates Neural Differentiation and Regeneration

AbstractConductive nerve guidance channels are promising alternative therapies in peripheral nerve tissue engineering because they have excellent biocompatibility, biodegradation, and electrical conductivity. Gold, a kind of conductive material, is investigated widely concerning its potential roles in promoting peripheral nerve repair. In the present study, a polydopamine‐coated gold/polycaprolactone nanoscaffold is fabricated via a multilayer molding method and its proliferative, adhesive, and neural differentiation potential for bone marrow mesenchymal stem cells (BMSCs) and Schwann cells (SCs) in vitro is evaluated. Functional, electrophysiological evaluation, and morphological assessment all exhibit satisfactory recovery of sciatic nerves with increased thickness and number of myelinated fibers in vivo. In addition, increased microvessels are confirmed in gold nanocomposite channels, indicating their potential benefits in angiogenesis. Functional regeneration is further enhanced by neurotrophic growth factors released from BMSC and SC loading. The gold nanocomposite channel will have great potential in peripheral nerve restoration.

Electrodeposition to construct mechanically robust chitosan-based multi-channel conduits.

A series of electrodeposited chitosan-based multi-channel conduits (ECMC) with potential for peripheral nerve tissue engineering were constructed using a novel electrodeposition method combined with homemade molds. The structural and mechanical properties of the ECMC were characterized by scanning electron microscopy, Fourier-transformed infrared spectroscopy, X-ray diffraction patterns and mechanical testing. The results showed that the electrodeposition process did not change the chemical structure of the chitosan molecules, but endowed the ECMC with high levels of flexibility and elasticity. Hemocompatibility and cytocompatibility of the ECMC were evaluated by hemolysis assay, MTT assay and live/dead assay. The results indicated that the ECMC had a low hemolysis rate, and can promote cell proliferation and support cell adhesion. This work provides a safe and feasible electrodeposition method to construct chitosan-based conduits with potential applications for peripheral nerve tissue engineering.

Dual Contribution of Mesenchymal Stem Cells Employed for Tissue Engineering of Peripheral Nerves: Trophic Activity and Differentiation into Connective-Tissue Cells.

Adult peripheral nerves in vertebrates can regrow their axons and re-establish function after crush lesion. However, when there is extensive loss of a nerve segment, due to an accident or compressive damage caused by tumors, regeneration is strongly impaired. In order to overcome this problem, bioengineering strategies have been employed, using biomaterials formed by key cell types combined with biodegradable polymers. Many of these strategies are successful, and regenerated nerve tissue can be observed 12 weeks after the implantation. Mesenchymal stem cells (MSCs) are one of the key cell types and the main stem-cell population experimentally employed for cell therapy and tissue engineering of peripheral nerves. The ability of these cells to release a range of different small molecules, such as neurotrophins, growth factors and interleukins, has been widely described and is a feasible explanation for the improvement of nerve regeneration. Moreover, the multipotent capacity of MSCs has been very often challenged with demonstrations of pluripotency, which includes differentiation into any neural cell type. In this study, we generated a biomaterial formed by EGFP-MSCs, constitutively covering microstructured filaments made of poly-ε-caprolactone. This biomaterial was implanted in the sciatic nerve of adult rats, replacing a 12-mm segment, inside a silicon tube. Our results showed that six weeks after implantation, the MSCs had differentiated into connective-tissue cells, but not into neural crest-derived cells such as Schwann cells. Together, present findings demonstrated that MSCs can contribute to nerve-tissue regeneration, producing trophic factors and differentiating into fibroblasts, endothelial and smooth-muscle cells, which compose the connective tissue.

Tissue-Engineered Peripheral Nerve Interfaces.

Research on neural interfaces has historically concentrated on development of systems for the brain; however, there is increasing interest in peripheral nerve interfaces (PNIs) that could provide benefit when peripheral nerve function is compromised, such as for amputees. Efforts focus on designing scalable and high-performance sensory and motor peripheral nervous system interfaces. Current PNIs face several design challenges such as undersampling of signals from the thousands of axons, nerve-fiber selectivity, and device-tissue integration. To improve PNIs, several researchers have turned to tissue engineering. Peripheral nerve tissue engineering has focused on designing regeneration scaffolds that mimic normal nerve extracellular matrix composition, provide advanced microarchitecture to stimulate cell migration, and have mechanical properties like the native nerve. By combining PNIs with tissue engineering, the goal is to promote natural axon regeneration into the devices to facilitate close contact with electrodes; in contrast, traditional PNIs rely on insertion or placement of electrodes into or around existing nerves, or do not utilize materials to actively facilitate axon regeneration. This review presents the state-of-the-art of PNIs and nerve tissue engineering, highlights recent approaches to combine neural-interface technology and tissue engineering, and addresses the remaining challenges with foreign-body response.

Fabrication and characterization of electrospun laminin-functionalized silk fibroin/poly(ethylene oxide) nanofibrous scaffolds for peripheral nerve regeneration.

The peripheral nerve regeneration is still one of the major clinical problems, which has received a great deal of attention. In this study, the electrospun silk fibroin (SF)/poly(ethylene oxide) (PEO) nanofibrous scaffolds were fabricated and functionalized their surfaces with laminin (LN) without chemical linkers for potential use in the peripheral nerve tissue engineering. The morphology, surface chemistry, thermal behavior and wettability of the scaffolds were examined to evaluate their performance by means of scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and water contact angle (WCA) measurements, respectively. The proliferation and viability of Schwann cells onto the surfaces of SF/PEO nanofibrous scaffolds were investigated using SEM and thiazolyl blue (MTT) assay. The results showed an improvement of SF conformation and surface hydrophilicity of SF/PEO nanofibers after methanol and O2 plasma treatments. The immunostaining observation indicated a continuous coating of LN on the scaffolds. Improving the surface hydrophilicity and LN functionalization significantly increased the cell proliferation and this was more prominent after 5 days of culture time. In conclusion, the obtained results revealed that the electrospun LN-functionalized SF/PEO nanofibrous scaffold could be a promising candidate for peripheral nerve tissue regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1595-1604, 2018.

Electrospun nerve guide scaffold of poly(ε-caprolactone)/collagen/nanobioglass: an in vitro study in peripheral nerve tissue engineering.

Among various methods, nerve tissue engineering (NTE) is one of the applicable methods to reconstruct damaged nerve tissues. Electrospinning technique and biomaterials are often considered to fabricate fibrous tissue engineered conduits which have great similarity to the extracellular matrix on fiber structure. Polymer blending is one of the most effective methods for the production of new materials with outstanding features. In this study, conduit structures as main part of the peripheral nerve regeneration based on polymer blend nanocomposites poly(ε-caprolactone)/collagen/nanobioglass (PCL/collagen/NBG) were manufactured by electrospinning technique. Various properties of electrospun mats were investigated by using contact angle, tensile, degradation time, porosity, scanning electron microscopy (SEM), Fourier-transform infrared (FTIR), and wide-angle X-ray scattering (WAXS). The SEM analysis was shown that size range and average pore size of polymer blend nanocomposite nanofibers were about 250-400 nm and 0.7 µm, respectively, with an optimum porosity of 62.5%. The XRD result was shown that synthesized nanoparticles of NBG had amorphous structures. Also, FTIR analysis indicated that good interaction between polymer-polymer macromolecules and polymer particles. The contact angle and tensile tests were indicated that electrospun webs showed good hydrophilicity and toughness properties. According to SEM, MTT assay and DAPI staining technique, the ability to support cell attachment and viability of samples were characterized. In vitro study indicated electrospun collagen/PCL/NBG nanofibrous conduit promoted Human Endometrial Stem cells (hEnSCs) adhesion and proliferation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1960-1972, 2017.

Novel flexible nerve conduits made of water-based biodegradable polyurethane for peripheral nerve regeneration.

Peripheral nerve conduits were fabricated from biodegradable polyurethane (PU) which was synthesized by a waterborne process. The biodegradable PU was based on poly(ε-caprolactone) diol and polyethylene butylene adipate diol (2:3 molar ratio) as the soft segment. Conduits formed by the freeze-drying process had asymmetric microporous structure. The PU nerve conduits were used to bridge a 10-mm gap in rat sciatic nerve. Nerve regeneration was evaluated by walking track analysis, magnetic resonance imaging (MRI), electrophysiological, and histological analyses. Results demonstrated that after 6 weeks, walking function was recovered by 40%. MR images showed that the transected nerve was reconnected after 3 weeks and the diameter of the regenerated nerve increased from 3 to 6 weeks. The nerve conduction velocity of the regenerated nerve reached 50% of the normal value after 6 weeks. Histological examination revealed that the cross-sectional area of the regenerated nerve at the midconduit was 0.24 mm2 after 6 weeks. The efficacy of PU nerve conduits based on functional recovery and histology was superior to that of commercial conduits (Neurotube). The PU nerve conduit developed in this study may be a potential candidate for clinical peripheral nerve tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1383-1392, 2017.

Fabrication and characterization of Antheraea pernyi silk fibroin-blended P(LLA-CL) nanofibrous scaffolds for peripheral nerve tissue engineering

Electrospun nanofibers have gained widespreading interest for tissue engineering application. In the present study, ApF/P(LLA-CL) nanofibrous scaffolds were fabricated via electrospinning. The feasibility of the material as tissue engineering nerve scaffold was investigated in vitro. The average diameter increased with decreasing the blend ratio of ApF to P(LLA-CL). Characterization of 13C NMR and FTIR clarified that there is no obvious chemical bond reaction between ApF and P(LLA-CL). The tensile strength and elongation at break increased with the content increase of P(LLA-CL). The surface hydrophilic property of nanofibrous scaffolds enhanced with the increased content of ApF. Cell viability studies with Schwann cells demonstrated that ApF/P(LLA-CL) blended nanofibrous scaffolds significantly promoted cell growth as compare to P(LLA-CL), especially when the weight ratio of ApF to P(LLA-CL) was 25:75. The present work provides a basis for further studies of this novel nanofibrous material (ApF/P(LLA-CL)) in peripheral nerve tissue repair or regeneration.

Combining Gene and Stem Cell Therapy for Peripheral Nerve Tissue Engineering.

Despite a substantially increased understanding of neuropathophysiology, insufficient functional recovery after peripheral nerve injury remains a significant clinical challenge. Nerve regeneration following injury is dependent on Schwann cells, the supporting cells in the peripheral nervous system. Following nerve injury, Schwann cells adopt a proregenerative phenotype, which supports and guides regenerating nerves. However, this phenotype may not persist long enough to ensure functional recovery. Tissue-engineered nerve repair devices containing therapeutic cells that maintain the appropriate phenotype may help enhance nerve regeneration. The combination of gene and cell therapy is an emerging experimental strategy that seeks to provide the optimal environment for axonal regeneration and reestablishment of functional circuits. This review aims to summarize current preclinical evidence with potential for future translation from bench to bedside.

Electrospun polycaprolactone/chitosan scaffolds for nerve tissue engineering: physicochemical characterization and Schwann cell biocompatibility

Electrospun polycaprolactone (PCL)/chitosan (CH) blend scaffolds with different CH weight ratios were prepared to study the effect of scaffold composition on its physicochemical and biological properties. Scanning electron microscopy showed bead-free homogeneous randomly arranged nanofibers whose average diameter decreased from 240 to 110 nm with increasing CH content. The infrared spectra of the PCL/CH blends were very similar to the neat PCL scaffold. Energy-dispersive x-ray spectroscopy analysis confirmed the presence of carbon, oxygen and nitrogen in the scaffolds, although fluorine—from chemicals used as solvent—was also detected. The water contact angle decreased from 113° (for PCL) to 52° with increasing chitosan content. The biocompatibility was evaluated using fibroblasts and Schwann cell (SC) cultures. Cytotoxicity assays using fibroblasts demonstrated that electrospun scaffolds could be considered as non-cytotoxic material. Biocompatibility tests also revealed that the SCs adhered to scaffolds with different CH content, although the formulation containing CH at 5 wt% exhibited the highest proliferation on days 1 and 3. A better cell distribution was observed in the CH/PCL blends than in the neat PCL or CH scaffolds, where the cells were clustered. Immunochemistry analysis confirmed that SCs expressed the specific p75 cell marker on the scaffolds, suggesting that PCL/CH scaffolds would be good candidates for peripheral nerve tissue engineering.

Prospects of peripheral nerve tissue engineering using nerve guide conduits based on silk fibroin protein and other biopolymers

ABSTRACTPeripheral nerve injuries face some clinical obstacles and unsatisfactory functional outcomes. The slow regeneration rate of defected nerve delays functional recovery. To date, various therapeutic agents are used to enhance the survival and regeneration capacity of damaged neurons. Among these, nerve guide conduits held promise for peripheral nerve regeneration, through the physical guidance of the injured nerve across the lesions. Many natural and synthetic polymers are used to produce nerve conduits. Biopolymer-based biomaterials offer important options in control of structure, morphology, and chemistry as reasonable substitutes or mimics of extracellular matrix systems. Silk protein fibroin as a biocompatible natural polymer, possesses biodegradability, tunable mechanical properties, process ability, and suitable for the peripheral nerve conduits. This review highlights recent advances in the use of silk-based conduits for peripheral nerve regeneration. Further, the development of nerve conduits based on other biopolymers, including chitosan, alginate, collagen, and gelatin is discussed and compared.

Covalent binding of placental derived proteins to silk fibroin improves schwann cell adhesion and proliferation.

Schwann cells play a key role in peripheral nerve regeneration. Failure in sufficient formation of Büngner bands due to impaired Schwann cell proliferation has significant effects on the functional outcome after regeneration. Therefore, the growth substrate for Schwann cells should be considered with highest priority in any peripheral nerve tissue engineering approach. Due to its excellent biocompatibility silk fibroin has most recently attracted considerable interest as a biomaterial for use as conduit material in peripheral nerve regeneration. In this study we established a protocol to covalently bind collagen and laminin, which have been isolated from human placenta, to silk fibroin utilizing carbodiimide chemistry. Altered adhesion, viability and proliferation of Schwann cells were evaluated. A cell adhesion assay revealed that the functionalization with both, laminin or collagen, significantly improved Schwann cell adhesion to silk fibroin. Moreover laminin drastically accelerated adhesion. Schwann cell proliferation and viability assessed with BrdU and MTT assay, respectively, were significantly increased in the laminin-functionalized groups. The results suggest beneficial effects of laminin on both, cell adhesion as well as proliferative behaviour of Schwann cells. To conclude, the covalent tailoring of silk fibroin drastically enhances its properties as a cell substratum for Schwann cells, which might help to overcome current hurdles bridging long distance gaps in peripheral nerve injuries with the use of silk-based nerve guidance conduits.

Assessment of degradation and biocompatibility of electrodeposited chitosan and chitosan-carbon nanotube tubular implants.

Designing three-dimensional tubular materials made of chitosan is still a challenging task. Availability of such forms is highly desired by tissue engineering, especially peripheral nerve tissue engineering. Aiming at this problem, we use an electrodeposition phenomenon in order to obtain chitosan and chitosan-carbon nanotube hydrogel tubular implants. The in vitro biocompatibility of the fabricated structures is assessed using a mouse hippocampal cell line (mHippoE-18). As both implants do not induce significant cytotoxicity, they are next subjected to in vitro degradation studies in the environment simulating in vivo conditions for specified periods of time: 7, 14, and 28 days. The mass loss of implants indicates their stability at the tested time period; therefore, the materials are subcutaneously implanted in Sprague Dawley rats. The explants are collected after 7, 14, and 28 days. The assessment of composition and changes in tissues surrounding the implanted materials is made in respect to surrounding tissue thickness as well as the number of blood vessels, macrophages, lymphocytes, and neutrophils. No symptoms of acute inflammation are noticed at any point in time. The observed regular healing process allows concluding that both chitosan and chitosan-carbon hydrogel tubular implants are biocompatible with high application potential in tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2701-2711, 2016.

Design and fabrication of a nanofibrous polycaprolactone tubular nerve guide for peripheral nerve tissue engineering using a two-pole electrospinning system

Nerve guidance conduits are considered to be the new generation of scaffolds designed for nerve disorders. A tubular construct with a highly aligned fibrous structure, mimicking the endoneurium layer surrounding inner axons of a nerve fascicle, is a suitable candidate for a nerve guide. In this paper a new approach for the fabrication of 3D tubular nerve guides is introduced using simulation of a two-pole electrospinning system and describing its mechanism. The structure of this scaffold is then optimized using the Taguchi statistical method and after morphological studies by scanning electron microscopy, the crystallinity, tensile strength and protein adsorption of these highly aligned fibres are investigated, comparing them with semi-aligned and random fibres produced via conventional mandrel electrospinning. Cell attachment, proliferation and migration of PC12 neuronal like cells are studied on highly aligned, semi aligned and random structures, and morphological change and elongation are observed in PC12 cells. The results of these studies suggest that conduits fabricated using two-pole electrospinning are a suitable and promising scaffold for peripheral and even spinal nerve regeneration. This nerve guide has a great potential for further advanced modifications and regeneration in higher levels.

Electroactive biodegradable polyurethane significantly enhanced Schwann cells myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering

Myelination of Schwann cells (SCs) is critical for the success of peripheral nerve regeneration, and biomaterials that can promote SCs' neurotrophin secretion as scaffolds are beneficial for nerve repair. Here we present a biomaterials-approach, specifically, a highly tunable conductive biodegradable flexible polyurethane by polycondensation of poly(glycerol sebacate) and aniline pentamer, to significantly enhance SCs' myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering. SCs are cultured on these conductive polymer films, and the biocompatibility of these films and their ability to enhance myelin gene expressions and sustained neurotrophin secretion are successfully demonstrated. The mechanism of SCs' neurotrophin secretion on conductive films is demonstrated by investigating the relationship between intracellular Ca2+ level and SCs' myelination. Furthermore, the neurite growth and elongation of PC12 cells are induced by adding the neurotrophin medium suspension produced from SCs-laden conductive films. These data suggest that these conductive degradable polyurethanes that enhance SCs' myelin gene expressions and sustained neurotrophin secretion perform great potential for nerve regeneration applications.

Application of marrow mesenchymal stem cell-derived extracellular matrix in peripheral nerve tissue engineering.

To advance molecular and cellular therapy into the clinic for peripheral nerve injury, modification of neural scaffolds with the extracellular matrix (ECM) of peripheral nerves has been established as a promising alternative to direct inclusion of support cells and/or growth factors within a neural scaffold, while cell-derived ECM proves to be superior to tissue-derived ECM in the modification of neural scaffolds. Based on the fact that bone marrow mesenchymal stem cells (BMSCs), just like Schwann cells, are adopted as support cells within a neural scaffold, in this study we used BMSCs as parent cells to generate ECM for application in peripheral nerve tissue engineering. A chitosan nerve guidance conduit (NGC) and silk fibroin filamentous fillers were respectively prepared for co-culture with purified BMSCs, followed by decellularization to stimulate ECM deposition. The ECM-modified NGC and lumen fillers were then assembled into a chitosan-silk fibroin-based, BMSC-derived, ECM-modified neural scaffold, which was implanted into rats to bridge a 10 mm-long sciatic nerve gap. Histological and functional assessments after implantation showed that regenerative outcomes achieved by our engineered neural scaffold were better than those achieved by a plain chitosan-silk fibroin scaffold, and suggested the benefits of BMSC-derived ECM for peripheral nerve repair. Copyright © 2016 John Wiley & Sons, Ltd.

Application of bone marrow mesenchymal stem cell-derived extracellular matrix in peripheral nerve tissue engineering

Event Abstract Back to Event Application of bone marrow mesenchymal stem cell-derived extracellular matrix in peripheral nerve tissue engineering Yun Gu1, Zhenmeiyu Li1, Chenbin Xue1, Shen Yi1 and Xiaosong Gu1 1 Nantong University, Jiangsu Key Laboratory of Neuroregeneration, China Objective: To advance molecular and cellular therapy into the clinic for peripheral nerve injury, modification of neural scaffolds with the extracellular matrix (ECM) of peripheral nerves has been established as a promising alternative to direct inclusion of support cells and/or growth factors within a neural scaffold, while the cell-derived ECM proves to be superior to the tissue-derived ECM in modification of neural scaffolds. Based on the fact that bone marrow mesenchymal stem cells (BMSCs), just like Schwann cells, are adopted as support cells within a neural scaffold, in this study, we used BMSCs as parent cells to generate ECM for application in peripheral nerve tissue engineering. Methods: A chitosan nerve guidance conduit (NGC) and silk fibroin filamentous fillers were respectively prepared for co-culture with purified BMSCs respectively, followed by decellularization to stimulate ECM deposition. The ECM modified NGC and lumen fillers were then assembled into a chitosan/silk fibroin-based, BMSC-derived ECM modified neural scaffold, which was implanted into rats to bridge a 10-mm long sciatic nerve gap. After nerve grafting 12 weeks, a series of histological and functional assessments were conducted to compare the regenerative outcomes between MSC-ECM and Scaffold groups. Results: (1) Light and electron micrography were used to observe the topological structure of the BMSC-derived ECM, and immunostaining was performed to identify the protein composition of the BMSC-derived ECM. These results showed that the ECM ultrastructure consistied of a dense meshwork of filamentous and granular materials. (2)A animal model of peripheral nerve injury was adopted in this study to investigate the performances of the BMSC-derived ECM modified neural scaffolds. Anti-NF immunostaining demonstrated that the length or the number of regenerating nerve fibers was significantly greater in MSC-ECM group than in Scaffold group. Electrophysiological assessments were used to evaluate the effects of BMSC-derived ECM modified neural scaffolds on functional recovery. In this study, we noted that the regenerative outcomes were significantly larger in MSC-ECM group than in Scaffold group, suggesting that BMSC-derived ECM had promoting effects on motor function restoration. Finally, morphological observation of regenerated nerve fibers under TEM and the related morphometric analysis revealed that myelin sheath formation was promoted by BMSC-derived ECM modified scaffolds as compared to that by plain scaffolds. Collectively, the comprehensive data from histological and functional examinations suggest that regenerative outcomes achieved by our engineered neural scaffold were better than those by a plain chitosan/silk fibroin scaffold, and suggested the benefits of BMSC-derived ECM for peripheral nerve repair. Conclusion: We have prepared a novel neural scaffold for peripheral nerve repair. A chitosan NGC and silk fibroin filamentous fillers were respectively prepared, and then co-cultured with purified BMSCs respectively, followed by decellularization to stimulate ECM deposition. The ECM modified NGC and lumen fillers were assembled into a chitosan/SF-based, BMSC-derived ECM modified neural scaffold, which was used to bridge a 10 mm long sciatic nerve gap in rats. Histological and functional assessments after scaffold grafting showed that regenerative outcomes achieved by our developed scaffold were better than those by a plain chitosan/silk fibroin scaffold. National Natural Science Foundation of China (Grant Nos. 81200932 and 81471255); Basic Research Program of Jiangsu Education Department (Grant No. 14KJA310004)

Tissue-engineered rhesus monkey nerve grafts for the repair of long ulnar nerve defects: similar outcomes to autologous nerve grafts.

Acellular nerve allografts can help preserve normal nerve structure and extracellular matrix composition. These allografts have low immunogenicity and are more readily available than autologous nerves for the repair of long-segment peripheral nerve defects. In this study, we repaired a 40-mm ulnar nerve defect in rhesus monkeys with tissue-engineered peripheral nerve, and compared the outcome with that of autograft. The graft was prepared using a chemical extract from adult rhesus monkeys and seeded with allogeneic Schwann cells. Pathomorphology, electromyogram and immunohistochemistry findings revealed the absence of palmar erosion or ulcers, and that the morphology and elasticity of the hypothenar eminence were normal 5 months postoperatively. There were no significant differences in the mean peak compound muscle action potential, the mean nerve conduction velocity, or the number of neurofilaments between the experimental and control groups. However, outcome was significantly better in the experimental group than in the blank group. These findings suggest that chemically extracted allogeneic nerve seeded with autologous Schwann cells can repair 40-mm ulnar nerve defects in the rhesus monkey. The outcomes are similar to those obtained with autologous nerve graft.