Modern Trends for Peripheral Nerve Repair and Regeneration: Beyond the Hollow Nerve Guidance Conduit

Carvalho, Cristiana R.; Oliveira, Joaquim M.; Reis, Rui L.

doi:10.3389/fbioe.2019.00337

Cited by 297Nerve injury and regenerationTissue Engineering and Regenerative MedicineNeuroscience and Neural Engineering

Modern Trends for Peripheral Nerve Repair and Regeneration: Beyond the Hollow Nerve Guidance Conduit

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Carvalho, Cristiana R., Oliveira, Joaquim M., Reis, Rui L.·2019·Frontiers in Bioengineering and Biotechnology

DOI 10.3389/fbioe.2019.00337PMC PMC6882937

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Abstract

Peripheral nerve repair and regeneration remains among the greatest challenges in tissue engineering and regenerative medicine. Even though peripheral nerve injuries (PNIs) are capable of some degree of regeneration, frail recovery is seen even when the best microsurgical technique is applied. PNIs are known to be very incapacitating for the patient, due to the deprivation of motor and sensory abilities. Since there is no optimal solution for tackling this problem up to this day, the evolution in the field is constant, with innovative designs of advanced nerve guidance conduits (NGCs) being reported every day. As a basic concept, a NGC should act as a physical barrier from the external environment, concomitantly acting as physical guidance for the regenerative axons across the gap lesion. NGCs should also be able to retain the naturally released nerve growth factors secreted by the damaged nerve stumps, as well as reducing the invasion of scar tissue-forming fibroblasts to the injury site. Based on the neurobiological knowledge related to the events that succeed after a nerve injury, neuronal subsistence is subjected to the existence of an ideal environment of growth factors, hormones, cytokines, and extracellular matrix (ECM) factors. Therefore, it is known that multifunctional NGCs fabricated through combinatorial approaches are needed to improve the functional and clinical outcomes after PNIs. The present work overviews the current reports dealing with the several features that can be used to improve peripheral nerve regeneration (PNR), ranging from the simple use of hollow NGCs to tissue engineered intraluminal fillers, or to even more advanced strategies, comprising the molecular and gene therapies as well as cell-based therapies.

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PNS exhibits greater reparative capacity and more favorable prognosis, providing promising application scenario for tissue engineering materials.
“Consequently, the PNS exhibits greater reparative capacity and a more favorable prognosis, which also provides a promising application scenario for tissue engineering materials [178].”
From Application of PLCL as a biodegradable polymer in biomedical engineering (2026) · cites this paper as [178]
The Introduction (page unavailable) describes peripheral nerves’ capacity to regenerate, and the Tissue Engineering and Regenerative Medicine Concepts for PNR section discusses biomaterial scaffolds for their repair. The paper does not establish the claimed greater reparative capacity or more favorable prognosis relative to the CNS; its Introduction cautions that treatments ensuring complete recovery are rare. (LLM, conf=0.83)
Experimental — accuracy not yet measured
Peripheral nervous system injury typically does not directly damage neuronal cell body but involves axonal breakage and myelin destruction.
“Injury to the PNS typically does not directly damage the neuronal cell body but rather involves axonal breakage and myelin destruction [178].”
From Application of PLCL as a biodegradable polymer in biomedical engineering (2026) · cites this paper as [178]
The Introduction describes axons collapsing and Schwann cells discarding their myelin after peripheral nerve injury; Figure 2 also describes axonal disintegration and myelin degradation. It does not specifically establish that injury typically spares the neuronal cell body. Its statement that cells in the distal nerve stump were not initially injured does not identify those cells as neuronal cell bodies. (LLM, conf=0.85)
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Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics
Carnicer-Lombarte, A., Chen, S.-T., Malliaras, G. G., & Barone, D. G. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.622524 · Cited by 454 · see citing works
“The field of surgical nerve repair already employs implants actively modulating biological processes (Carvalho et al., 2019), and may be a useful source for the development of new-generation nerve neuroprosthetics.”
Background
Multifunctional GelMA platforms with nanomaterials for advanced tissue therapeutics
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Exosomes as a Promising Therapeutic Strategy for Peripheral Nerve Injury
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Electroactive nanomaterials in the peripheral nerve regeneration
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Fabrication and in vitro evaluation of 3D composite scaffold based on collagen/hyaluronic acid sponge and electrospun polycaprolactone nanofibers for peripheral nerve regeneration
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Angiogenesis in Disease
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Bridging Gaps in Peripheral Nerves: From Current Strategies to Future Perspectives in Conduit Design
Stocco, E., Barbon, S., Emmi, A., Tiengo, C., Macchi, V., De, R., & Porzionato, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24119170 · Cited by 78 · see citing works
Interaction between Schwann cells and other cells during repair of peripheral nerve injury
Tian, H., Chen, B., Li, R., Qu, W., Zhu, Z., Liu, J., Song, D.-B., & Deng, L. (2020) · Neural Regeneration Research · doi:10.4103/1673-5374.286956 · Cited by 76 · see citing works
Biofabrication of aligned structures that guide cell orientation and applications in tissue engineering
Lu, K., Qian, Y., Gong, J., Zhu, Z., Yin, J., Ma, L., Yu, M., & Wang, H. (2021) · Bio-Design and Manufacturing · doi:10.1007/s42242-020-00104-5 · Cited by 73 · see citing works
Physical stimuli-emitting scaffolds: The role of piezoelectricity in tissue regeneration
Alvarez‐Lorenzo, C., Zarur, M., Seijo-Rabina, A., Blanco‐Fernandez, B., Rodríguez‐Moldes, I., & Concheiro, Á. (2023) · Materials Today Bio · doi:10.1016/j.mtbio.2023.100740 · Cited by 67 · see citing works
Advances in Biomimetic Nerve Guidance Conduits for Peripheral Nerve Regeneration
Mankavi, F., Ibrahim, R., & Wang, H. (2023) · Nanomaterials · doi:10.3390/nano13182528 · Cited by 64 · see citing works
Repair of peripheral nerve injuries using a prevascularized cell-based tissue-engineered nerve conduit
Thibodeau, A., Galbraith, T., Fauvel, C. M., Khuong, H. T., & Berthod, F. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.121269 · Cited by 58 · see citing works
Chitosan nanoparticles, as biological macromolecule-based drug delivery systems to improve the healing potential of artificial neural guidance channels: A review
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A hyaluronic acid granular hydrogel nerve guidance conduit promotes regeneration and functional recovery of injured sciatic nerves in rats
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3D Gelatin Microsphere Scaffolds Promote Functional Recovery after Spinal Cord Hemisection in Rats
Ke, H., Yang, H., Zhao, Y., Li, T., Xin, D., Gai, C., Jiang, Z., & Wang, Z. (2022) · Advanced Science · doi:10.1002/advs.202204528 · Cited by 54 · see citing works
Combining a Density Gradient of Biomacromolecular Nanoparticles with Biological Effectors in an Electrospun Fiber‐Based Nerve Guidance Conduit to Promote Peripheral Nerve Repair
Jin, B., Yu, Y., Lou, C., Zhang, X., Gong, B., Chen, J., Chen, X., Zhou, Z., Zhang, L., Xiao, J., et al. (2022) · Advanced Science · doi:10.1002/advs.202203296 · Cited by 54 · see citing works
Use of the CatWalk gait analysis system to assess functional recovery in rodent models of peripheral nerve injury – a systematic review
Heinzel, J. C., Laengle, G., Oberhauser, V., Hausner, T., Kolbenschlag, J., Prahm, C., Grillari, J., & Hercher, D. (2020) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2020.108889 · Cited by 50 · see citing works
Cryogel biomaterials for neuroscience applications
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Li–Mg–Si bioceramics provide a dynamic immuno-modulatory and repair-supportive microenvironment for peripheral nerve regeneration
Sun, Y., Zhang, H., Zhang, Y., Liu, Z., He, D., Xu, W., Li, S., Zhang, C., & Zhang, Z. (2023) · Bioactive Materials · doi:10.1016/j.bioactmat.2023.05.013 · Cited by 50 · see citing works
Advancing Peripheral Nerve Regeneration: 3D Bioprinting of GelMA-Based Cell-Laden Electroactive Bioinks for Nerve Conduits
Das, S., Jegadeesan, J. T., & Basu, B. (2024) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.3c01226 · Cited by 49 · see citing works
The progress of biomaterials in peripheral nerve repair and regeneration
Wang, Y., Zhang, Y., Li, X., & Zhang, Q. (2020) · Journal of Neurorestoratology · doi:10.26599/jnr.2020.9040022 · Cited by 47 · see citing works
Simultaneous Regeneration of Bone and Nerves Through Materials and Architectural Design: Are We There Yet?
Wan, Q., Qin, W., Shen, M., Ma, Y., Li, B., Liu, S., Tay, F. R., Jiao, K., & Niu, L. (2020) · Advanced Functional Materials · doi:10.1002/adfm.202003542 · Cited by 46 · see citing works
Electroceuticals for peripheral nerve regeneration
Maeng, W., Tseng, W., Li, S., Koo, J., & Hsueh, Y. (2022) · Biofabrication · doi:10.1088/1758-5090/ac8baa · Cited by 45 · see citing works
Additive Manufacturing of Polyhydroxyalkanoate-Based Blends Using Fused Deposition Modelling for the Development of Biomedical Devices
Gregory, D. A., Fricker, A. T. R., Mitrev, P., Ray, M., Asare, E., Sim, D., Larpnimitchai, S., Zhang, Z., Ma, J., Tetali, S. S. V., et al. (2023) · Journal of Functional Biomaterials · doi:10.3390/jfb14010040 · Cited by 45 · see citing works
Silk-based biomaterials for tissue engineering
Zhang, T., Zhang, R., Zhang, Y., Kannan, P. R., Li, Y., Lv, Y., Zhao, R., & Kong, X. (2025) · Advances in Colloid and Interface Science · doi:10.1016/j.cis.2025.103413 · Cited by 44 · see citing works
Additive manufacturing of peripheral nerve conduits – Fabrication methods, design considerations and clinical challenges
Zennifer, A., Thangadurai, M., Sundaramurthi, D., & Sethuraman, S. (2023) · SLAS TECHNOLOGY · doi:10.1016/j.slast.2023.03.006 · Cited by 43 · see citing works
Beyond the limiting gap length: peripheral nerve regeneration through implantable nerve guidance conduits
Riva, E. R., Özkan, M., Contreras, E., Pawar, S., Zinno, C., Escarda‐Castro, E., Kim, J., Wieringa, P. A., Stellacci, F., Micera, S., et al. (2024) · Biomaterials Science · doi:10.1039/d3bm01163a · Cited by 43 · see citing works
Electrical aligned polyurethane nerve guidance conduit modulates macrophage polarization and facilitates immunoregulatory peripheral nerve regeneration
Sun, Y., Zhang, Y., Guo, Y., He, D., Xu, W., Fang, W., Zhang, C., Zuo, Y., & Zhang, Z. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02507-3 · Cited by 43 · see citing works
Defining the regenerative effects of native spider silk fibers on primary Schwann cells, sensory neurons, and nerve‐associated fibroblasts
Millesi, F., Weiss, T., Mann, A., Haertinger, M., Semmler, L., Supper, P., Pils, D., Naghilou, A., & Radtke, C. (2020) · The FASEB Journal · doi:10.1096/fj.202001447r · Cited by 39 · see citing works
Combined Use of Chitosan and Olfactory Mucosa Mesenchymal Stem/Stromal Cells to Promote Peripheral Nerve Regeneration In Vivo
Alvites, R., Branquinho, M., Sousa, A. C., Amorim, I., Magalhães, R. M., João, F., Almeida, D., Amado, S., Prada, J., Pires, I. C. R., et al. (2021) · Stem Cells International · doi:10.1155/2021/6613029 · Cited by 41 · see citing works
Schwann cell delivery via a novel 3D collagen matrix conduit improves outcomes in critical length nerve gap repairs
Burks, S. S., Diaz, A., Haggerty, A. E., de la Oliva, N., Midha, R., & Levi, A. D. (2021) · Journal of neurosurgery · doi:10.3171/2020.8.jns202349 · Cited by 41 · see citing works
Human umbilical cord mesenchymal stem cell-derived exosomes loaded into a composite conduit promote functional recovery after peripheral nerve injury in rats
Tang, H., Li, J., Wang, H., Ren, J., Ding, H., Shang, J., Wang, M., Wei, Z., & Feng, S. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.380911 · Cited by 41 · see citing works
State of the Art and Current Challenges on Electroactive Biomaterials and Strategies for Neural Tissue Regeneration
Marques‐Almeida, T., Lanceros-Méndez, S., & Ribeiro, C. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202301494 · Cited by 40 · see citing works
Natural polysaccharides and their derivatives as potential medical materials and drug delivery systems for the treatment of peripheral nerve injuries
Solomevich, S. O., Oranges, C. M., Kalbermatten, D. F., Schwendeman, A. A., & Madduri, S. (2023) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2023.120934 · Cited by 39 · see citing works
Synthetic materials in craniofacial regenerative medicine: A comprehensive overview
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Conductive Hydroxyethyl Cellulose/Soy Protein Isolate/Polyaniline Conduits for Enhancing Peripheral Nerve Regeneration via Electrical Stimulation
Wu, P., Zhao, Y., Chen, F., Xiao, A., Du, Q., Dong, Q., Ke, M., Liang, X., Zhou, Q., & Chen, Y. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00709 · Cited by 38 · see citing works
Carboxymethylchitosan hydrogel manufactured by radiation-induced crosslinking as potential nerve regeneration guide scaffold
Wach, R. A., Adamus-Włodarczyk, A., Olejnik, A. K., Matusiak, M., Tranquilan‐Aranilla, C., & Ulański, P. (2020) · Reactive and Functional Polymers · doi:10.1016/j.reactfunctpolym.2020.104588 · Cited by 36 · see citing works
Typical and atypical properties of peripheral nerve allografts enable novel strategies to repair segmental-loss injuries
Bittner, G. D., Bushman, J. S., Ghergherehchi, C. L., Roballo, K. C. S., Shores, J. T., & Smith, T. A. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02395-0 · Cited by 37 · see citing works
Silk‐in‐Silk Nerve Guidance Conduits Enhance Regeneration in a Rat Sciatic Nerve Injury Model
Semmler, L., Naghilou, A., Millesi, F., Wolf, S., Mann, A., Stadlmayr, S., Mero, S., Ploszczanski, L., Greutter, L., Wöehrer, A., et al. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202203237 · Cited by 35 · see citing works
Experimental Study on Repairing Peripheral Nerve Defects with Novel Bionic Tissue Engineering
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Authors: Carvalho, C. R., Oliveira, J. M., & Reis, R. L.
Affiliations: 3B's Research Group (PT)
Corresponding author: Oliveira, Joaquim M.
ORCID: Carvalho, Cristiana R.
Oliveira, Joaquim M.
Reis, Rui L.
Venue: Frontiers in Bioengineering and Biotechnology
Publisher: Frontiers Media SA
Published: 2019-11-22
Volume: 7
Pages: 337-337
ISSN: 2296-4185 (ISSN-L)
DOI: 10.3389/fbioe.2019.00337
PMC: PMC6882937
OpenAlex: W2990818690
Cited by: 297
References: 244
Citations by year: 2026: 32 · 2025: 34 · 2024: 45 · 2023: 64 · 2022: 54 · 2021: 44 · 2020: 23 · 2019: 1
FWCI: 4.05
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Frontiers in Bioengineering and Biotechnology (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by-nc-nd)
Funders: Horizon 2020 Framework Programme
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
Keywords: peripheral nerve repair, peripheral nerve regeneration, nerve conduits, peripheral nerve injury, nerve growth factor, scar formation, extracellular matrix, gene therapy, cell therapy, tissue engineering

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Modern Trends for Peripheral Nerve Repair and Regeneration: Beyond the Hollow Nerve Guidance Conduit

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