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      Advances in novel biomaterials combined with traditional Chinese medicine rehabilitation technology in treatment of peripheral nerve injury

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          Abstract

          Peripheral nerve injuries (PNI) represent one of the primary neuropathies leading to lifelong disability. Nerve regeneration and targeted muscle atrophy stand as the two most crucial factors influencing functional rehabilitation post peripheral nerve injury. Over time, traditional Chinese medicine (TCM) rehabilitation approaches such as acupuncture, Tuina, and microneedles serve as pivot means to activate the regeneration of injured nerve Schwann cells. By promoting axon regeneration, these approaches can accomplish nerve repair, reconstruction, and functional rehabilitation. Although TCM rehabilitation approaches have clinically demonstrated effectiveness in promoting the repair and regeneration of PNI, the related molecular mechanisms remain unclear. This significantly hampers the application and promotion of TCM rehabilitation in PNI recovery. Therefore, deeply delving into the cellular and molecular mechanisms of TCM rehabilitation technologies to foster nerve regeneration stands as the most pressing issue. On the other hand, in recent years, novel biomaterials represented by hydrogels, microfluidic platforms, and new chitosan scaffolds have showed their unique roles in treating various degrees of nerve injury. These methods exhibit immense potential in conducting high-throughput cell and organoid culture in vitro and synthesizing diverse tissue engineering scaffolds and drug carriers. We believe that the combination of TCM rehabilitation technology and novel biomaterials can more effectively address precise treatment issues such as identification of treatment target and dosage control. Therefore, this paper not only summarizes the molecular mechanisms of TCM rehabilitation technology and novel biomaterials in treating peripheral nerve injury individually, but also explores the research direction of precise treatment by integrating the two at both macro and micro levels. Such integration may facilitate the exploration of cellular and molecular mechanisms related to neurodegeneration and regeneration, providing a scientific and theoretical foundation for the precise functional rehabilitation of PNI in the future.

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          Most cited references90

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          Microneedles for drug and vaccine delivery.

          Microneedles were first conceptualized for drug delivery many decades ago, but only became the subject of significant research starting in the mid-1990's when microfabrication technology enabled their manufacture as (i) solid microneedles for skin pretreatment to increase skin permeability, (ii) microneedles coated with drug that dissolves off in the skin, (iii) polymer microneedles that encapsulate drug and fully dissolve in the skin and (iv) hollow microneedles for drug infusion into the skin. As shown in more than 350 papers now published in the field, microneedles have been used to deliver a broad range of different low molecular weight drugs, biotherapeutics and vaccines, including published human studies with a number of small-molecule and protein drugs and vaccines. Influenza vaccination using a hollow microneedle is in widespread clinical use and a number of solid microneedle products are sold for cosmetic purposes. In addition to applications in the skin, microneedles have also been adapted for delivery of bioactives into the eye and into cells. Successful application of microneedles depends on device function that facilitates microneedle insertion and possible infusion into skin, skin recovery after microneedle removal, and drug stability during manufacturing, storage and delivery, and on patient outcomes, including lack of pain, skin irritation and skin infection, in addition to drug efficacy and safety. Building off a strong technology base and multiple demonstrations of successful drug delivery, microneedles are poised to advance further into clinical practice to enable better pharmaceutical therapies, vaccination and other applications. Copyright © 2012 Elsevier B.V. All rights reserved.
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            The repair Schwann cell and its function in regenerating nerves

            Abstract Nerve injury triggers the conversion of myelin and non‐myelin (Remak) Schwann cells to a cell phenotype specialized to promote repair. Distal to damage, these repair Schwann cells provide the necessary signals and spatial cues for the survival of injured neurons, axonal regeneration and target reinnervation. The conversion to repair Schwann cells involves de‐differentiation together with alternative differentiation, or activation, a combination that is typical of cell type conversions often referred to as (direct or lineage) reprogramming. Thus, injury‐induced Schwann cell reprogramming involves down‐regulation of myelin genes combined with activation of a set of repair‐supportive features, including up‐regulation of trophic factors, elevation of cytokines as part of the innate immune response, myelin clearance by activation of myelin autophagy in Schwann cells and macrophage recruitment, and the formation of regeneration tracks, Bungner's bands, for directing axons to their targets. This repair programme is controlled transcriptionally by mechanisms involving the transcription factor c‐Jun, which is rapidly up‐regulated in Schwann cells after injury. In the absence of c‐Jun, damage results in the formation of a dysfunctional repair cell, neuronal death and failure of functional recovery. c‐Jun, although not required for Schwann cell development, is therefore central to the reprogramming of myelin and non‐myelin (Remak) Schwann cells to repair cells after injury. In future, the signalling that specifies this cell requires further analysis so that pharmacological tools that boost and maintain the repair Schwann cell phenotype can be developed.
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              Schwann Cells: Development and Role in Nerve Repair.

              Schwann cells develop from the neural crest in a well-defined sequence of events. This involves the formation of the Schwann cell precursor and immature Schwann cells, followed by the generation of the myelin and nonmyelin (Remak) cells of mature nerves. This review describes the signals that control the embryonic phase of this process and the organogenesis of peripheral nerves. We also discuss the phenotypic plasticity retained by mature Schwann cells, and explain why this unusual feature is central to the striking regenerative potential of the peripheral nervous system (PNS).
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/1816574/overviewRole: Role:
                URI : https://loop.frontiersin.org/people/2749615/overviewRole: Role:
                Role: Role: Role:
                Role: Role: Role:
                Role: Role: Role:
                Role: Role: Role:
                Role: Role:
                URI : https://loop.frontiersin.org/people/1700795/overviewRole: Role: Role: Role:
                Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/2191268/overviewRole: Role: Role: Role: Role:
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                13 June 2024
                2024
                : 15
                : 1421772
                Affiliations
                [1] 1The Second Rehabilitation Hospital of Shanghai , Shanghai, China
                [2] 2Shanghai University of Traditional Chinese Medicine , Shanghai, China
                [3] 3Department of Acupuncture, Shanghai Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine , Shanghai, China
                Author notes

                Edited by: Guocheng Fang, Nanyang Technological University, Singapore

                Reviewed by: Shi Jia Tang, Nanjing Medical University, China

                Ke Hu, Nanjing Medical University, China

                *Correspondence: Shujie Ma, mashujie86@ 123456163.com

                These authors have contributed equally to this work

                Article
                10.3389/fneur.2024.1421772
                11208681
                38938781
                03bc83d3-5aad-4da6-8054-cb80be37767d
                Copyright © 2024 Liu, Hu, Huang, Hu, Lu, Chen, Xue, Ma, Wan and Hu.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 May 2024
                : 03 June 2024
                Page count
                Figures: 3, Tables: 0, Equations: 0, References: 90, Pages: 11, Words: 9457
                Funding
                The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This publication of this review paper was supported by the Medical Key Specialized Project of Baoshan District (Grant No. BSZK-2023-BZ12), the Science and Technology Foundation Project of Baoshan District (Grant No. 20-E-43), the National Natural Science Foundation of China (Grant Nos 81603713, 82304446).
                Categories
                Neurology
                Review
                Custom metadata
                Neuromuscular Disorders and Peripheral Neuropathies

                Neurology
                novel biomaterials,traditional chinese medicine,rehabilitation,peripheral nerve injury,microfluidic chip

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