Repair of extended peripheral nerve lesions in rhesus monkeys using acellular allogenic nerve grafts implanted with autologous mesenchymal stem cells

Despite intensive efforts in the field of peripheral nerve injury and regeneration, it remains difficult in humans to achieve full functional recovery following extended peripheral nerve lesions. Optimizing repair of peripheral nerve injuries has been hindered by the lack of viable and reliable biologic or artificial nerve conduits for bridging extended gaps. In this study, we utilized chemically extracted acellular allogenic nerve segments implanted with autologous non-hematopoietic mesenchymal stem cells (MSCs) to repair a 40 mm defect in the rhesus monkey ulnar nerve. We found that severely damaged ulnar nerves were structurally and functionally repaired within 6 months following placement of the MSC seeded allografts in all animals studied (6 of 6, 100%). Furthermore, recovery with the MSC seeded allografts was similar to that observed with Schwann cell seeded allografts and autologous nerve grafts. The findings presented here are the first demonstration of the successful use of autologous MSCs, expanded in culture and implanted in a biological conduit, to repair a peripheral nerve gap in primates. Given the difficulty in isolating and purifying sufficient quantities of Schwann cells for peripheral nerve regeneration, the use of MSCs to seed acellular allogenic nerve grafts may prove to be a novel and promising therapeutic approach for repairing severe peripheral nerve injuries in humans.     

Combining acellular nerve allografis with brain- derived neurotrophic factor transfected bone marrow mesenchymal stem cells restores sciatic nerve injury better than either intervention alone

In this study, we chemically extracted acellular nerve allografts from bilateral sciatic nerves, and repaired 10-mm sciatic nerve defects in rats using these grafts and brain-derived neurotrophic factor transfected bone marrow mesenchymal stem cells. Experiments were performed in three groups： the acellular nerve allograft bridging group, acellular nerve allograft ＋ bone marrow mesenchymal stem cells group, and the acellular nerve allograft ＋ brain-derived neurotrophic factor transfected bone marrow mesenchyrnal stem cells group. Results showed that at 8 weeks after bridging, sciatic functional index, triceps wet weight recovery rate, myelin thickness, and number of myelinated nerve fibers were significantly changed in the three groups. Variations were the largest in the acellular nerve allograft ＋ brain-derived neurotrophic factor transfected bone marrow mesenchymal stem cells group compared with the other two groups. Experimental findings suggest that chemically extracted acellular nerve allograft combined nerve factor and mesenchymal stem cells can promote the restoration of sciatic nerve defects. The repair effect seen is better than the single application of acellular nerve allograft or acellular nerve allograft combined mesenchymal stem cell transplantation.     

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

Acellular nerve allogratfs can help preserve normal nerve structure and extracellular matrix composition. These allogratfs have low immu-nogenicity 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 autogratf. The gratf was prepared using a chemical extract from adult rhesus monkeys and seeded with allogeneic Schwann cells. Pathomo-rphology, electromyogram and immunohistochemistry ifndings 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 signiifcant differences in the mean peak compound muscle action potential, the mean nerve conduction velocity, or the number of neuroiflaments between the experimental and control groups. However, outcome was signiifcantly better in the experimental group than in the blank group. These ifndings 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 gratf.     

富血小板血浆诱导骨髓间充质干细胞修复坐骨神经缺损：并与自体神经修复的效果相比较

目的：通过植入经PRP诱导的BMSCs结合化学萃取的去细胞神经修复坐骨神经缺损,观察其对周围神经的修复作用。 方法：32只新西兰大耳白兔,随机分成4组,即单纯的化学萃取的去细胞神经、BMSCs结合化学萃取的去细胞神经、经PRP诱导的BMSCs结合化学萃取的去细胞神和自体神经修复坐骨神经缺损,检测指标包括形态学观察、靶肌肉肌湿重恢复率、运动神经传导速度（MNCV）及轴突直径和髓鞘厚度等。 结果：结果显示,靶肌肉肌湿重恢复率、MNCV、轴突直径和髓鞘厚度和形态学观察在经PRP诱导的BMSCs结合化学萃取的去细胞神经组明显优于单纯的化学萃取的去细胞神经组和BMSCs结合化学萃取的去细胞神经组,而与自体神经修复组结果相似。 结论：经诱导后的BMSCs在体内具有SC的部分功能,可作为组织工程化外周神经的种子细胞,用于周围神经缺损的修复。     

富血小板血浆诱导骨髓间充质干细胞结合化学萃取去细胞神经修复坐骨神经缺损

背景：周围神经损伤早期许旺细胞尚未大量分裂增殖,此时由于解剖连续性的中断,通过轴浆逆向运输提供的营养因子骤减,缺乏神经营养因子支持的神经元有可能死亡,从而使周围神经不能再生或再生乏力。 目的：观察植入经富血小板血浆诱导的骨髓间充质干细胞结合去细胞神经修复坐骨神经缺损的效果。 方法：取新西兰大耳白兔制备坐骨神经缺损模型,随机抽签法分成4组：去细胞神经组,移植同种异体去细胞神经;骨髓间充质干细胞组,移植同种异体骨髓间充质干细胞结合化学萃取的同种异体去细胞神经：经诱导骨髓间充质干细胞组,移植经富血小板血浆诱导的同种异体骨髓间充质干细胞结合化学萃取的同种异体去细胞神经;自体神经组,移植自体神经。术后进行形态学观察与靶肌肉肌湿质量恢复率、运动神经传导速度、轴突直径和髓鞘厚度的检测。 结果与结论：经富血小板血浆诱导的骨髓间充质干细胞结合化学萃取的去细胞神经移植修复神经的靶肌肉肌湿质量恢复率、运动神经传导速度、轴突直径和髓鞘厚度及形态学观察明显优于移植单纯化学萃取的去细胞神经与骨髓间充质干细胞结合化学萃取的去细胞神经的效果,而与移植自体神经修复结果相似。说明经诱导后的骨髓间充质干细胞在体内具有许旺细胞的部分功能,可作为组织工程化外周神经的种子细胞,用于周围神经缺损的修复。     

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.     

Sciatic nerve repair by acellular nerve xenografts implanted with BMSCs in rats xenograft combined with BMSCs

Acellular nerves possess the structural and biochemical features similar to those of naive endoneurial tubes, and have been proved bioactive for allogeneil graft in nerve tissue engineering. However, the source of allogenic donators is restricted in clinical treatment. To explore sufficient substitutes for acellular nerve allografts (ANA), we investigated the effectiveness of acellular nerve xenografts (ANX) combined with bone marrow stromal cells (BMSCs) on repairing peripheral nerve injuries. The acellular nerves derived from Sprague-Dawley rats and New Zealand rabbits were prepared, respectively, and BMSCs were implanted into the nerve scaffolds and cultured in vitro. All the grafts were employed to bridge 1 cm rat sciatic nerve gaps. Fifty Wistar rats were randomly divided into five groups (n = 10 per group): ANA group, ANX group, BMSCs-laden ANA group, BMSCs-laden ANX group, and autologous nerve graft group. At 8 weeks post-transplantation, electrophysiological study was performed and the regenerated nerves were assayed morphologically. Besides, growth-promoting factors in the regenerated tissues following the BMSCs integration were detected. The results indicated that compared with the acellular nerve control groups, nerve regeneration and functional rehabilitation for the xenogenic nerve transplantation integrated with BMSCs were advanced significantly, and the rehabilitation efficacy was comparable with that of the autografting. The expression of neurotrophic factors in the regenerated nerves, together with that of brain-derived neurotrophic factor (BDNF) in the spinal cord and muscles were elevated largely. In conclusion, ANX implanted with BMSCs could replace allografts to promote nerve regeneration effectively, which offers a reliable approach for repairing peripheral nerve defects.     

Acellular allogeneic nerve grafting combined with bone marrow mesenchymal stem cell transplantation for the repair of long-segment sciatic nerve defects:biomechanics and validation of mathematical models

We hypothesized that a chemically extracted acellular allogeneic nerve graft used in combination with bone marrow mesenchymal stem cell transplantation would be an effective treatment for long-segment sciatic nerve defects. To test this, we established rabbit models of 30 mm sciatic nerve defects, and treated them using either an autograft or a chemically decellularized allogeneic nerve graft with or without simultaneous transplantation of bone marrow mesenchymal stem cells. We compared the tensile properties, electrophysiological function and morphology of the damaged nerve in each group. Sciatic nerves repaired by the allogeneic nerve graft combined with stem cell trans-plantation showed better recovery than those repaired by the acellular allogeneic nerve graft alone, and produced similar results to those observed with the autograft. These ifndings conifrm that a chemically extracted acellular allogeneic nerve graft combined with transplanta-tion of bone marrow mesenchymal stem cells is an effective method of repairing long-segment sciatic nerve defects.     

Repair of peripheral nerve defects with chemically extracted acellular nerve allografts loaded with neurotrophic factors-transfected bone marrow mesenchymal stem cells

Chemically extracted acellular nerve allografts loaded with brain-derived neurotrophic factor-transfected or ciliary neurotrophic factor-transfected bone marrow mesenchymal stem cells have been shown to repair sciatic nerve injury better than chemically extracted acellular nerve allografts alone, or chemically extracted acellular nerve allografts loaded with bone marrow mesenchymal stem cells. We hypothesized that these allografts compounded with both brain-derived neurotrophic factor- and ciliary neurotrophic factor-transfected bone marrow mesenchymal stem cells may demonstrate even better effects in the repair of peripheral nerve injury. We cultured bone marrow mesenchymal stem cells expressing brain-derived neurotrophic factor and/or ciliary neurotrophic factor and used them to treat sciatic nerve injury in rats. We observed an increase in sciatic functional index, triceps wet weight recovery rate, myelin thickness, number of myelinated nerve fibers, amplitude of motor-evoked potentials and nerve conduction velocity, and a shortened latency of motor-evoked potentials when allografts loaded with both neurotrophic factors were used, compared with allografts loaded with just one factor. Thus, the combination of both brain-derived neurotrophic factor and ciliary neurotrophic factor-transfected bone marrow mesenchymal stem cells can greatly improve nerve injury.     

Synergistic effects of G‐CSF and bone marrow stromal cells on nerve regeneration with acellular nerve xenografts

Peripheral nerve defects result in severe denervation presenting sensory and motor functional incapacitation. Currently, a satisfactory therapeutic treatment promoting the repair of injured nerves is not available. As shown in our previous study, acellular nerve xenografts (ANX) implanted with bone marrow stromal cells (BMSCs) replaced allografts and promoted nerve regeneration. Additionally, granulocyte‐colony stimulating factor (G‐CSF) has been proven to mobilize supplemental cells and enhance vascularization in the niche. Thus, the study aimed to explore whether the combination of G‐CSF and BMSC‐laden ANX exhibited a synergistic effect. Adult Sprague‐Dawley (SD) rats were randomly divided into five groups: ANX group, ANX combined with G‐CSF group, BMSCs‐laden ANX group, BMSCs‐laden ANX combined with G‐CSF group and autograft group. Electrophysiological parameters and weight ratios of tibialis anterior muscles were detected at 8 weeks post‐transplantation. The morphology of the regenerated nerves was assayed, and growth‐promoting factors present in the nerve grafts following G‐CSF administration or BMSCs seeding were also investigated. Nerve regeneration and functional rehabilitation induced by the combination therapy were significantly advanced, and the rehabilitation efficacy was comparable with autografting. Moreover, the expression of Schwann cell markers, neurotrophic factors and neovessel markers in the nerve grafts was substantially increased. In conclusion, G‐CSF administration and BMSCs transplantation synergistically promoted the regeneration of ANX‐bridged nerves, which offers a superior strategy to replace autografts in repairing peripheral nerve injuries.     

Chemically extracted aceUular allogeneic nerve graft combined with ciliary neurotrophic factor promotes sciatic nerve repair

A chemically extracted acellular allogeneic nerve graft can reduce postoperative immune rejection, similar to an autologous nerve graft, and can guide neural regeneration. However, it remains poorly understood whether a chemically extracted acellular allogeneic nerve graft combined with neurotrophic factors provides a good local environment for neural regeneration. This study investigated the repair of injured rat sciatic nerve using a chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor. An autologous nerve anastomosis group and a chemical acellular allogeneic nerve bridging group were prepared as controls. At 8 weeks after repair, sciatic functional index, evoked potential amplitude of the soleus muscle, triceps wet weight recovery rate, total number of myelinated nerve fibers and myelin sheath thickness were measured. For these indices, values in the three groups showed the autologous nerve anastomosis group 〉 chemically extracted acellular nerve graft ＋ ciliary neurotrophic factor group 〉 chemical acellular allogeneic nerve bridging group. These results suggest that chemically extracted acellular nerve grafts combined with ciliary neurotrophic factor can repair sciatic nerve defects, and that this repair is inferior to autologous nerve anastomosis, but superior to chemically extracted acellular allogeneic nerve bridging alone.     

化学去细胞异体神经进趋化性再生的作用

Acellular nerve allograft preserves the basilar membrane tube and extracellular matrix, which pro-motes selective regeneration of neural defects via bridging. In the present study, a Sprague Dawley rat sciatic nerve was utilized to prepare acellular nerve allografts through the use of the chemical extraction method. Subsequently, the allograft was transplanted into a 10-mm sciatic nerve defect in Wistar rats, while autologous nerve grafts from Wistar rats served as controls. Compared with autologous nerve grafts, the acellular nerve allografts induced a greater number of degenerated nerve fibers from sural nerves, as well as a reduced misconnect rate in motor fibers, fewer acetyl-choline esterase-positive sural nerves, and a greater number of carbonic anhydrase-positive sen-sory nerve fibers. Results demonstrated that the acellular nerve allograft exhibited significant neural selective regeneration in the process of bridging nerve defects.     

Combining acellular nerve allografts with brainderived neurotrophic factor transfected bone marrow mesenchymal stem cells restores sciatic nerve injury better than either intervention alone

In this study,we chemically extracted acellular nerve allografts from bilateral sciatic nerves,and repaired 10-mm sciatic nerve defects in rats using these grafts and brain-derived neurotrophic factor transfected bone marrow mesenchymal stem cells.Experiments were performed in three groups: the acellular nerve allograft bridging group,acellular nerve allograft + bone marrow mesenchymal stem cells group,and the acellular nerve allograft + brain-derived neurotrophic factor transfected bone marrow mesenchymal stem cells group.Results showed that at 8 weeks after bridging,sciatic functional index,triceps wet weight recovery rate,myelin thickness,and number of myelinated nerve fibers were significantly changed in the three groups.Variations were the largest in the acellular nerve allograft + brain-derived neurotrophic factor transfected bone marrow mesenchymal stem cells group compared with the other two groups.Experimental findings suggest that chemically extracted acellular nerve allograft combined nerve factor and mesenchymal stem cells can promote the restoration of sciatic nerve defects.The repair effect seen is better than the single application of acellular nerve allograft or acellular nerve allograft combined mesenchymal stem cell transplantation.     

Chemoattractive capacity of different lengths of nerve fragments bridging regeneration chambers for the repair of sciatic nerve defects

A preliminary study by our research group showed that 6-mm-long regeneration chamber bridging is equivalent to autologous nerve transplantation for the repair of 12-mm nerve defects. In this study, we compared the efficacy of different lengths (6, 8, 10 mm) of nerve fragments bridging 6-mm regeneration chambers for the repair of 12-mm-long nerve defects. At 16 weeks after the regeneration chamber was implanted, the number, diameter and myelin sheath thickness of the regenerated nerve fibers, as well as the conduction velocity of the sciatic nerve and gastrocnemius muscle wet weight ratio, were similar to that observed with autologous nerve transplantation. Our results demonstrate that 6-, 8-and 10-mm-long nerve fragments bridging 6-mm regeneration chambers effec-tively repair 12-mm-long nerve defects. Because the chemoattractive capacity is not affected by the length of the nerve fragment, we suggest adopting 6-mm-long nerve fragments for the repair of peripheral nerve defects.     

Acellular nerve allografts in peripheral nerve regeneration: a comparative study

Introduction: Processed nerve allografts offer a promising alternative to nerve autografts in the surgical management of peripheral nerve injuries where short deficits exist. Methods: Three established models of acellular nerve allograft (cold‐preserved, detergent‐processed, and AxoGen‐processed nerve allografts) were compared with nerve isografts and silicone nerve guidance conduits in a 14‐mm rat sciatic nerve defect. Results: All acellular nerve grafts were superior to silicone nerve conduits in support of nerve regeneration. Detergent‐processed allografts were similar to isografts at 6 weeks postoperatively, whereas AxoGen‐processed and cold‐preserved allografts supported significantly fewer regenerating nerve fibers. Measurement of muscle force confirmed that detergent‐processed allografts promoted isograft‐equivalent levels of motor recovery 16 weeks postoperatively. All acellular allografts promoted greater amounts of motor recovery compared with silicone conduits. Conclusion: These findings provide evidence that differential processing for removal of cellular constituents in preparing acellular nerve allografts affects recovery in vivo. Muscle Nerve, 2011     

Nerve guides seeded with autologous schwann cells improve nerve regeneration

This study evaluates the ability of Schwann cells (SCs) transplanted into a nerve guide to improve regeneration and reinnervation after sciatic nerve resection and repair, leaving a 6-mm gap, in the mouse. SCs were isolated from predegenerated adult sciatic nerves and expanded in culture using a chemically defined medium. Syngeneic, isogeneic, and autologous SCs were suspended in Matrigel and seeded in resorbable, permeable poly(l-lactide-co-epsilon-caprolactone) guides at 150,000 cells/tube. Guides containing SCs were compared to guides filled with Matrigel alone and with peroneal nerve autografts. Functional reinnervation was assessed by noninvasive methods to determine recovery of sweating, nociceptive, sensory, and motor functions in the hindpaw during 4 months postoperation. Morphological analysis of the regenerated nerves was performed at the end of follow-up. The group with an autograft achieved faster and higher levels of reinnervation and higher number of regenerated myelinated fibers than groups repaired by tubulization. The immunogenicity of transplanted SCs influenced the outcome of nerve regeneration. Transplants of autologous SCs resulted in slightly lower levels of reinnervation than autografts, but higher recovery and number of regenerated fibers reaching the distal nerve than transplants of isologous and syngeneic SCs, although most of the differences were not statistically significant. Syngeneic SCs did not improve regeneration with respect to acellular guides. Prelabeled transplanted SCs were found to survive into the guide 1-3 months after implantation, to a larger number when they were autologous than syngeneic. Cellular prostheses composed of a resorbable guide seeded with autologous SCs appear as an alternative for repairing long gaps in injured nerves, approaching the success of autografts.     

Combination of BMSCs‐laden acellular nerve xenografts transplantation and G‐CSF administration promotes sciatic nerve regeneration

Peripheral nerve gaps often lead to interrupted innervation, manifesting as severe sensory and motor dysfunctions. The repairs of the nerve injuries have not achieved satisfactory curative effects in clinic. The transplantation of bone marrow stromal cells (BMSCs)‐laden acellular nerve xenografts (ANX) has been proven more effective than the acellular nerve allografting. Besides, granulocyte colony‐stimulating factor (G‐CSF) can inhibit inflammation and apoptosis, and thus is conducive to the microenvironmental improvement of axonal regeneration. This study aims to investigate the joint effect of BMSCs‐seeded ANX grafting and G‐CSF administration, and explore the relevant mechanisms. Adult SD rats were divided into five groups randomly: ANX group, ANX combined with G‐CSF group, BMSCs‐laden ANX group, BMSCs‐laden ANX combined with G‐CSF group, and autograft group. Eight weeks after transplantation, the detection of praxiology and neuroelectrophysiology was conducted, and then the morphology of the regenerated nerves was analyzed. The inflammatory response and apoptosis in the nerve grafts as well as the expression of the growth‐promoting factors in the regenerated tissues were further assayed. G‐CSF intervention and BMSCs implanting synergistically promoted peripheral nerve regeneration and functional recovery following ANX bridging, and the restoration effect was matchable with that of the autologous nerve grafting. Moreover, local inflammation was alleviated, the apoptosis of the seeded BMSCs was decreased, and the levels of the neuromodulatory factors were elevated. In conclusion, the union application of BMSCs‐implanted ANX and G‐CSF ameliorated the niche of neurotization and advanced nerve regeneration substantially. The strategy achieved the favorable effectiveness as an alternative to the autotransplantation.     

Advances in the repair of segmental nerve injuries and trends in reconstruction

Despite advances in surgery, the reconstruction of segmental nerve injuries continues to pose challenges. In this review, current neurobiology regarding regeneration across a nerve defect is discussed in detail. Recent findings include the complex roles of nonneuronal cells in nerve defect regeneration, such as the role of the innate immune system in angiogenesis and how Schwann cells migrate within the defect. Clinically, the repair of nerve defects is still best served by using nerve autografts with the exception of small, noncritical sensory nerve defects, which can be repaired using autograft alternatives, such as processed or acellular nerve allografts. Given current clinical limits for when alternatives can be used, advanced solutions to repair nerve defects demonstrated in animals are highlighted. These highlights include alternatives designed with novel topology and materials, delivery of drugs specifically known to accelerate axon growth, and greater attention to the role of the immune system.     

Immunohistochemical assessment of rat nerve isografts and immunosuppressed allografts

Objective: Autologous peripheral nerve grafts are commonly used clinically as a treatment for peripheral nerve injuries. However, in research using an autologous graft is not always feasible due to loss of function, which in many cases is assessed to determine the efficacy of the peripheral nerve graft. In addition, using allografts for research require the use of an immunosuppressant, which creates unwanted side effects and another variable within the experiment that can affect regeneration. The objective of this study was to analyze graft rejection in peripheral nerve grafts and the effects of cyclosporine A (CSA) on axonal regeneration.

Methods: Peripheral nerve grafts in inbred Lewis rats were compared with Sprague-Dawley (SD) rats to assess graft rejection, CSA side effects, immune responses, and regenerative capability. Macrophages and CD8+ cells were labeled to determine graft rejection, and neurofilaments were labeled to determine axonal regeneration.

Results: SD rats without CSA had significantly more macrophages and CD8+ cells compared to Lewis autografts, Lewis isografts, and SD allografts treated with CSA. Lewis autografts, Lewis isografts, and SD autografts had significantly more regenerated axons than SD rat allografts. Moreover, allografts in immunosuppressed SD rats had significantly less axons than Lewis rat autograft and isografts.

Discussion: Autografts have long been the gold standard for treating major nerve injuries and these data suggest that even though CSA is effective at reducing graft rejection, axon regeneration is still superior in autografts versus immunosuppressed allografts.     

Biological conduits combining bone marrow mesenchymal stem cells and extracellular matrix to treat long-segment sciatic nerve defects

The transplantation of polylactic glycolic acid conduits combining bone marrow mesenchymal stem cells and extracellular matrix gel for the repair of sciatic nerve injury is effective in some respects, but few data comparing the biomechanical factors related to the sciatic nerve are available. In the present study, rabbit models of 10-mm sciatic nerve defects were prepared. The rabbit models were repaired with autologous nerve, a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells, or a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel. After 24 weeks, mechanical testing was performed to determine the stress relaxation and creep parameters. Following sciatic nerve injury, the magnitudes of the stress decrease and strain increase at 7,200 seconds were largest in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group, followed by the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group, and then the autologous nerve group. Hematoxylin-eosin staining demonstrated that compared with the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group and the autologous nerve group, a more complete sciatic nerve regeneration was found, including good myelination, regularly arranged nerve fibers, and a completely degraded and resorbed conduit, in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group. These results indicate that bridging 10-mm sciatic nerve defects with a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel construct increases the stress relaxation under a constant strain, reducing anastomotic tension. Large elongations under a constant physiological load can limit the anastomotic opening and shift, which is beneficial for the regeneration and functional reconstruction of sciatic nerve. Better regeneration was found with the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel grafts than with the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells grafts and the autologous nerve grafts.