This article selects 7 original studies published from 2007 to 2025, covering teams from the United States, Singapore, China, Brazil, and other regions, with a focus on peripheral nerve repair. The article is a narrative review of representative literature and does not combine different defect models or outcome measures into a unified conclusion on efficacy.
01What Tasks Must Nerve Repair Materials Accomplish?
Fibrous materials for nerve repair can take different forms: planar aligned substrates for cell culture, conduits for bridging defects, and guiding sheets or fiber bundles placed inside the lumen. These three address, respectively, whether cells respond to directional cues, whether the conduit wall can maintain a patently open channel, and whether regenerating tissue can traverse the defect and reestablish connections with target tissue.1,2,3,4
| Sample morphology | Problems to Be Addressed | Corresponding evaluations are required |
|---|---|---|
| Aligned Fiber Culture Substrates | Providing Directional Cues for Neurites and Support Cells | Cell Viability, Migration, Neurite Length, and Alignment 1,2 |
| Tubular Nerve Guidance Conduits | Establishing and Maintaining a Bridging Space | Wet-State Lumen, Conduit Wall Stability, Suturing Procedures, and Tissue Response 3 |
| Internal Fibers and Functional Composite Layers of the Conduit | Combining Morphological Guidance with Local Biological Effects | Axons and Myelin Sheaths, Neuroelectrophysiology, Muscle, and Motor Performance 4,7 |
These tasks are interrelated but not equivalent. Cells growing along fibers on a planar surface provide evidence of guidance; when the material is rolled into a conduit, the inner diameter, wall thickness, pores, seams, and available space for cell entry must also be considered. Conduit materials cannot be evaluated solely by tensile strength; maintaining patency after wetting and bending is equally important.3,6
02How to Combine Aligned Fibers and Tubular Structures
Polyesters such as polylactic acid (PLLA), polycaprolactone (PCL), polylactic acid-caprolactone copolymers (PLCL), and PLGA, as well as natural components such as chitosan and gelatin, have all appeared in relevant studies. Material selection affects fiber formation, surface cell interactions, wet-state mechanics, and degradation; fiber orientation adds spatial cues to which cells can respond.1,2,3,5,6
Designing Internal Guidance and External Support Separately
One design approach arranges axially aligned fibers on the inner lumen while using randomly oriented fibers externally to maintain structural integrity. Another approach first prepares a planar membrane, then rolls it up or places it within an existing tube. Different pathways require separate examination of inner-wall orientation, seams, and interlayer bonding; orientation statistics from planar membranes cannot substitute for structural assessment after tubular formation.3,4
Surface Treatment Must Be Evaluated Together with Wet-State Stability
Natural polymers or surface treatments may alter cell adhesion, as well as fiber diameter, swelling, and alignment. Studies of gelatin-treated PLGA and genipin-crosslinked chitosan both demonstrate that, after functionalization, the complete sample should be re-examined rather than assuming that pre-treatment geometry remains unchanged.5,6
03Whether Orientation Is Useful: First Examine Cellular Responses
In a 2007 study by Corey et al., PLLA fibers with varying degrees of alignment were compared, and dorsal root ganglion explants were cultured. After contacting the fibers, neurites extended along the fiber direction, and substrates with higher alignment supported longer neurites in this experiment. This provides in vitro evidence of direct morphological guidance; however, the subjects evaluated were ex vivo neural tissues, not patients undergoing repair surgery.1
In human Schwann cell cultures studied by Chew and others in 2008, aligned PCL fibers were observed to cause cells to elongate and align along the fiber axis, while also altering the expression of certain myelin-related genes. This work extended orientation research from neurons to support cells, but human cell experiments remain in vitro studies and cannot be labeled as human nerve repair trials.2
04Conduit Design Must Balance Axial Guidance and Structural Retention
In a 2011 study by Zhu et al., a seamless dual-layer conduit was prepared by one-step electrospinning, with longitudinally aligned fibers on the inner layer and randomly oriented fibers on the outer layer. It was compared with randomly fibrous conduits and autografts in a rat sciatic nerve defect model. The study combined histomorphology, electrophysiology, and behavioral observations, demonstrating the potential of layered structures for nerve regeneration. The design value lies in constructing the guiding interface together with the overall conduit wall; this result cannot be used to conclude that all dual-layer conduits will achieve the same outcome.3
In a 2018 study by Lau et al., genipin treatment was investigated to improve the stability of chitosan fibers in physiological environments. Treated fibers exhibited improved resistance to swelling, enzymatic degradation, and morphological change, and their guiding performance was evaluated in Schwann cell and dorsal root ganglion explant experiments. This work represents material and in vitro evaluation, demonstrating that maintaining directional cues requires first maintaining wet-state structure.5
05Functional Composite Structures Combine Guidance with Local Effects
In a 2007 study by Chew et al., glial cell line-derived neurotrophic factor (GDNF) was incorporated into electrospun PCLEEP copolymer fibers, which were then combined with a conduit structure to study rat 15 mm sciatic nerve defects. The authors observed bridging of regenerating tissue and electrophysiological recovery in some animals, indicating that incorporating the factor into fibers offers the possibility of combining spatial guidance with biochemical cues. Successful bridging and complete functional recovery should be understood as distinct outcomes and not treated as interchangeable.4
In a 2025 study by Song et al., a helical conductive PLCL/HEC-PEDOT conduit was prepared with an internal aligned fiber membrane. The study examined Schwann cell and PC12 cell behavior and reported improvements in regeneration, angiogenesis, and function-related outcomes in a sciatic nerve defect animal model. The relevant takeaway here is the integrated design of internal conduit structure, electrical properties, and biological evaluation; the results derive from a specific composite system and cannot be interpreted as demonstrating that “conductivity” is universally effective for repair.7
Such composite approaches require separate description of the fiber framework, functional components, and post-treatments. If proteins or conductive layers are introduced, active ingredient retention, release or electrical stability, component distribution, and local tissue response should also be verified, rather than selecting a design based solely on dry-state morphology or a single conductivity measurement.4,7
06How to Distinguish Between Biocompatibility and Nerve Function Recovery
In a 2021 study by Pozzobon et al., aligned PLGA fibers were prepared and gelatin-treated to form a nerve conduit. Cells remained viable and proliferated over 7 days of culture, but the sciatic nerve function index observed at 8 weeks in the rat injury model was similar to that of the injury control group, showing no significant functional improvement. This result indicates that cell growth does not necessarily mean the conduit has resolved defect bridging or functional recovery.6
The materials, defect lengths, observation periods, and functional endpoints used in the above studies differ. When comparing approaches, axonal morphology, myelin sheaths, electrophysiology, muscle status, and motor performance should be interpreted within their respective models. The evidence selected for this article is confined to in vitro and animal stages and cannot be used to claim that a specific electrospun nerve conduit has obtained human efficacy validation.1,2,3,4,5,6,7
07From Oriented Membranes to Reproducible Conduit Samples
Clarify whether the intended product is a membrane sheet or a complete nerve guidance conduit
Planar oriented samples can be used to screen materials and assess cellular responses; complete nerve guidance conduits require advance specification of inner diameter, length, wall thickness, inner-wall fiber orientation, and operational requirements. Equipment configuration should be discussed in relation to these sample specifications, including oriented collection, rotating mandrels, layer-by-layer deposition, and fluid supply stability.
Maintaining orientation does not mean indefinitely increasing the collection speed
Collection conditions can be compared alongside fiber diameter, alignment distribution, pore structure, and wet-state mechanical properties. After changing the collector or sample dimensions, axial and circumferential deposition differences should be reconfirmed; multilayer samples also require checking the orientation and connection of each layer, rather than measuring only the total thickness.3,5,6
Include post-processing in the process record
Crosslinking, surface modification, drying, demolding, and sterilization may affect the final structure. These steps can be correlated with batch, wet-state dimensions, and biological testing; the equipment is responsible for controllable fiber formation and collection, while the performance of the nerve guidance conduit still needs to be established through specific materials and product validation.
08Common issues in nerve guidance conduit development
Are finer fibers always more beneficial for nerve repair?
Diameter alone cannot be used for ranking. Alignment, density, cellular access space, wet-state structure, and surface properties jointly influence outcomes and should be compared within the same model.1,2,3,5
Do experiments using human Schwann cells constitute human studies?
No. They indicate the response of human cells to materials under experimental conditions and must still be distinguished from animal implantation and patient studies.2
Can planar oriented membranes be directly rolled into conduits?
This preparation approach is reported in the literature, but after rolling, seams, lumen, inner-wall orientation, and wet-state integrity must be checked. Direct tube formation and layer-by-layer collection can also be discussed; their respective suitability should be determined by sample validation.3,6
References
The following are the original studies used in this document. TONGLI independently summarizes the literature and does not reproduce original figures or tables; the listed authors and institutions are not presented as TONGLI client cases. The scope and validation stage of each conclusion should be understood according to the main text and original publications.
Bibliographic records retain the original publication language for accurate lookup.
Corey JM, Lin DY, Mycek KB, et al. Aligned electrospun nanofibers specify the direction of dorsal root ganglia neurite growth. Journal of Biomedical Materials Research Part A, 2007, 83(3):636–645.
DOI：10.1002/jbm.a.31285 ↗Scope of reading: PubMed original study abstracts and bibliographies
Chew SY, Mi R, Hoke A, Leong KW. The effect of the alignment of electrospun fibrous scaffolds on Schwann cell maturation. Biomaterials, 2008, 29(6):653–661.
DOI：10.1016/j.biomaterials.2007.10.025 ↗Scope of reading: PubMed original abstracts and bibliographies; year of formal publication 2008
Zhu Y, Wang A, Patel S, et al. Engineering bi-layer nanofibrous conduits for peripheral nerve regeneration. Tissue Engineering Part C: Methods, 2011, 17(7):705–715.
DOI：10.1089/ten.tec.2010.0565 ↗Scope of reading: publicly available excerpts from methods and discussions in the original papers PMC; bibliography PubMed
Chew SY, Mi R, Hoke A, Leong KW. Aligned protein–polymer composite fibers enhance nerve regeneration: A potential tissue-engineering platform. Advanced Functional Materials, 2007, 17(8):1288–1296.
DOI：10.1002/adfm.200600441 ↗Scope of reading: publicly available abstracts, results, and conclusions from the original papers PMC
Lau YT, Kwok LF, Tam KW, et al. Genipin-treated chitosan nanofibers as a novel scaffold for nerve guidance channel design. Colloids and Surfaces B: Biointerfaces, 2018, 162:126–134.
DOI：10.1016/j.colsurfb.2017.11.061 ↗Scope of reading: locally extracted original text PDF, including the homepage and results; online version 2017 and published version 2018
Pozzobon LG, Sperling LE, Teixeira CE, Malysz T, Pranke P. Development of a conduit of PLGA-gelatin aligned nanofibers produced by electrospinning for peripheral nerve regeneration. Chemico-Biological Interactions, 2021, 348:109621.
DOI：10.1016/j.cbi.2021.109621 ↗Scope of reading: locally extracted original text PDF, including the homepage and methods; retain negative in vivo results
Song J, Wu S, Liao C, et al. Spiral-structured electrospun conductive conduits filled with aligned nanofibers for peripheral nerve regeneration. Chemical Engineering Journal, 2025, 508:160899.
DOI：10.1016/j.cej.2025.160899 ↗Scope of reading: original study abstracts and bibliographies from the publisher
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