Functionalized nerve conduits for peripheral nerve regeneration: A literature review

Regas, Inès; Loisel, François; Haight, Harrison; Menu, Gauthier; Obert, L.; Pluvy, I.

doi:10.1016/j.hansur.2020.05.007

Cited by 21 publications

(11 citation statements)

References 76 publications

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“…Since Millesi et al published the successful reconstruction of peripheral nerve defects with ANG, no other reconstruction concept was able to show superiority [ 1 , 2 , 14 ]. At best, artificial nerve conduits or alternative concepts, such as processed allografts of human nerves, led to functional results such as ANG [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Closing the Gap: Bridging Peripheral Sensory Nerve Defects with a Chitosan-Based Conduit a Randomized Prospective Clinical Trial

Aman

Kneser

Harhaus

et al. 2022

JPM

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Introduction: If tensionless nerve coaptation is not possible, bridging the resulting peripheral nerve defect with an autologous nerve graft is still the current gold standard. The concept of conduits as an alternative with different materials and architectures, such as autologous vein conduits or bioartificial nerve conduits, could not replace the nerve graft until today. Chitosan, as a relatively new biomaterial, has recently demonstrated exceptional biocompatibility and material stability with neural lineage cells. The purpose of this prospective randomized clinical experiment was to determine the efficacy of chitosan-based nerve conduits in regenerating sensory nerves in the hand. Materials and methods: Forty-seven patients with peripheral nerve defects up to 26 mm distal to the carpal tunnel were randomized to receive either a chitosan conduit or an autologous nerve graft with the latter serving as the control group. Fifteen patients from the conduit group and seven patients from the control group were available for a 12-month follow-up examination. The primary outcome parameter was tactile gnosis measured with two-point discrimination. The secondary outcome parameters were Semmens Weinstein Monofilament Testing, self-assessed pain, and patient satisfaction. Results: Significant improvement (in static two-point discrimination) was observed six months after trauma (10.7 ± 1.2 mm; p < 0.05) for chitosan-based nerve conduits, but no further improvement was observed after 12 months of regeneration (10.9 ± 1.3 mm). After six months and twelve months, the autologous nerve graft demonstrated comparable results to the nerve conduit, with a static two-point discrimination of 11.0 ± 2.0 mm and 7.9 ± 1.1 mm. Semmes Weinstein Filament Testing in the nerve conduit group showed a continuous improvement over the regeneration period by reaching from 3.1 ± 0.3 after three months up to 3.7 ± 0.4 after twelve months. Autologous nerve grafts presented similar results: 3.3 ± 0.4 after three months and 3.7 ± 0.5 after twelve months. Patient satisfaction and self-reported pain levels were similar between the chitosan nerve conduit and nerve graft groups. One patient required revision surgery due to complications associated with the chitosan nerve tube. Conclusion: Chitosan-based nerve conduits are safe and suitable for bridging nerve lesions up to 26 mm in the hand. Tactile gnosis improved significantly during the early regeneration period, and functional outcomes were similar to those obtained with an autologous nerve graft. Thus, chitosan appears to be a sufficient substitute for autologous nerve grafts in the treatment of small nerve defects in the hand.

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Section: Discussionmentioning

confidence: 99%

Closing the Gap: Bridging Peripheral Sensory Nerve Defects with a Chitosan-Based Conduit a Randomized Prospective Clinical Trial

Aman

Kneser

Harhaus

et al. 2022

JPM

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“…In recent years, the combination of stem cell biology, biomaterial science, and tissue engineering technologies has shed light on developing different cell-based TE/RM products for efficacious therapy of PNIs [ 12 , 13 ]. Due to the critical role in peripheral nerve repair/regeneration following injury, primary autologous or allogeneic Schwann cells may represent the most effective type of supportive cells to aid regeneration after they are transplanted to the nerve injury site [ 5 , 8 ].…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, much progress has been made in fabricating functionalized nerve guidance conduits loaded with different types of bioactive noncellular or cellular components, particularly the combination with multipotent mesenchymal stem cells (MSCs) of different tissue origins, including dental tissues [ 12 , 13 ]. Accumulating evidence has shown that MSC-based tissue engineering and regenerative therapy holds great promise to promote nerve regeneration because of the potent immunomodulatory/anti-inflammatory functions and multifaced trophic effects of MSCs, such as neurotrophic or neuroprotective, pro-angiogenic, antioxidant, and anti-fibrotic effects due to their paracrine secretion of a myriad of biological factors [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Implantation of a nerve protector embedded with human GMSC-derived Schwann-like cells accelerates regeneration of crush-injured rat sciatic nerves

et al. 2022

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Background Peripheral nerve injuries (PNIs) remain one of the great clinical challenges because of their considerable long-term disability potential. Postnatal neural crest-derived multipotent stem cells, including gingiva-derived mesenchymal stem cells (GMSCs), represent a promising source of seed cells for tissue engineering and regenerative therapy of various disorders, including PNIs. Here, we generated GMSC-repopulated nerve protectors and evaluated their therapeutic effects in a crush injury model of rat sciatic nerves. Methods GMSCs were mixed in methacrylated collagen and cultured for 48 h, allowing the conversion of GMSCs into Schwann-like cells (GiSCs). The phenotype of GiSCs was verified by fluorescence studies on the expression of Schwann cell markers. GMSCs encapsulated in the methacrylated 3D-collagen hydrogel were co-cultured with THP-1-derived macrophages, and the secretion of anti-inflammatory cytokine IL-10 or inflammatory cytokines TNF-α and IL-1β in the supernatant was determined by ELISA. In addition, GMSCs mixed in the methacrylated collagen were filled into a nerve protector made from the decellularized small intestine submucosal extracellular matrix (SIS-ECM) and cultured for 24 h, allowing the generation of functionalized nerve protectors repopulated with GiSCs. We implanted the nerve protector to wrap the injury site of rat sciatic nerves and performed functional and histological assessments 4 weeks post-surgery. Results GMSCs encapsulated in the methacrylated 3D-collagen hydrogel were directly converted into Schwann-like cells (GiSCs) characterized by the expression of S-100β, p75NTR, BDNF, and GDNF. In vitro, co-culture of GMSCs encapsulated in the 3D-collagen hydrogel with macrophages remarkably increased the secretion of IL-10, an anti-inflammatory cytokine characteristic of pro-regenerative (M2) macrophages, but robustly reduced LPS-stimulated secretion of TNF-1α and IL-1β, two cytokines characteristic of pro-inflammatory (M1) macrophages. In addition, our results indicate that implantation of functionalized nerve protectors repopulated with GiSCs significantly accelerated functional recovery and axonal regeneration of crush-injured rat sciatic nerves accompanied by increased infiltration of pro-regenerative (M2) macrophages while a decreased infiltration of pro-inflammatory (M1) macrophages. Conclusions Collectively, these findings suggest that Schwann-like cells converted from GMSCs represent a promising source of supportive cells for regenerative therapy of PNI through their dual functions, neurotrophic effects, and immunomodulation of pro-inflammatory (M1)/pro-regenerative (M2) macrophages.

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“…6,7 Therefore, development of artificial nerve guidance conduits (NGCs) with biodegradable and biocompatible properties is considered a promising alternative to nerve autografts. [8][9][10][11] The extracellular matrix (ECM) plays several crucial roles in the development, regeneration, and maintenance of the PNS 12 and may be of value for engineering NGCs. Laminins are prominent components of the ECM in the PNS and have been shown to support axon growth as well as Schwann cell migration in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, limited availability and loss of function at the donor site restrict the use of autografts 6,7 . Therefore, development of artificial nerve guidance conduits (NGCs) with biodegradable and biocompatible properties is considered a promising alternative to nerve autografts 8–11 …”

Section: Introductionmentioning

confidence: 99%

Artificial spider silk supports and guides neurite extension in vitro

et al. 2021

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Functionalized nerve conduits for peripheral nerve regeneration: A literature review

Cited by 21 publications

References 76 publications

Closing the Gap: Bridging Peripheral Sensory Nerve Defects with a Chitosan-Based Conduit a Randomized Prospective Clinical Trial

Closing the Gap: Bridging Peripheral Sensory Nerve Defects with a Chitosan-Based Conduit a Randomized Prospective Clinical Trial

Implantation of a nerve protector embedded with human GMSC-derived Schwann-like cells accelerates regeneration of crush-injured rat sciatic nerves

Artificial spider silk supports and guides neurite extension in vitro

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