This article selects 6 original studies published from 2016 to 2024, involving teams and collaborative work from China, the United Kingdom, the United States, Ireland, and South Korea, and presents a narrative review. “Other tissues” are exemplified by skeletal muscle cultures; the selected literature covers materials, in vitro studies, and animal studies, but does not include human efficacy trials.
01Tendons, cartilage, and muscles require different structural solutions
Fibrous structures can be used in all these directions, but they cannot share a single “higher performance is better” criterion. Tendon and ligament research often focuses on axial tensile properties and cell alignment; cartilage research must simultaneously address compression, hierarchical structure, and matrix formation; skeletal muscle research links cell alignment, myotube formation, and coculture with vascular-related cells.1,2,3,4,5,6
| Application | Structural forms in research | Corresponding Evaluations |
|---|---|---|
| Tendon and ligament repair | Oriented membranes, rolled fiber bundles, and woven/electrospun composites | Tensile properties, tissue infiltration, collagen alignment, and repair strength 1,2 |
| Cartilage tissue engineering | Zoned scaffolds, fiber-reinforced matrices, and core-shell carriers | Compression, cell phenotype, cartilage matrix, and defect repair 3,4,5 |
| Skeletal muscle tissue engineering | Oriented fibers and supporting frameworks, with cell coculture | Myocyte alignment, myotube formation, and differentiation markers 6 |
Tendon repair scaffolds should also be distinguished from tendon anti-adhesion barrier membranes. The former aims to enable target cell infiltration and formation of organized tissue, whereas the latter focuses on isolating surrounding tissues and protecting a sliding interface. Even when the same material is used, the pore structures and surface requirements of these two sample types may differ; this article discusses structures for tissue repair.1,2
02Which step does electrospinning perform in composite scaffolds?
The electrospun layer can serve as the main component or merely provide contact guidance, interface regulation, or local delivery. Oriented membranes can be further rolled into bundles and combined with structures woven from coarser yarns; for cartilage applications, electrospun fibers can also be dispersed as short fibers into a printable matrix. Before selecting a process, determine whether the fibers will remain continuous, be bundled, be deposited in layers, or be dispersed as a reinforcing component.1,2,4
Studies combining multiple processes are particularly noteworthy. Woven frameworks or printed structures can provide macroscale shape and support, whereas fine fibers regulate the local environment of cell contact. The final outcome belongs to the entire composite system and requires simultaneous validation of fiber orientation, porosity, interfacial bonding, and wet-state mechanical properties; the overall performance of a composite scaffold cannot be attributed to a single piece of equipment or a single process step.2,3,4,6
03Tendons and Ligaments: From Oriented Membranes to Graded Composite Scaffolds
Using the same PCL, varying the arrangement and bundle-winding methods
Pauly et al. (2016) compared planar membranes made from random or oriented PCL fibers with wound fiber bundles, examining the effects of geometric morphology on mechanical properties and cellular behavior. The study found that different structures exhibited distinct moduli, yielding behaviors, and cell spreading; adipose-derived stem cells remained active and proliferated during 7 days of culture. This materials and in vitro study demonstrates that the organization of fibers is itself a design variable, not merely a matter of polymer formulation.1
The paper correlates certain mechanical indicators with the range observed in natural ligaments, but this does not mean that the fiber bundles can already replace ligaments in the human body. For repair structures subjected to repeated tensile loading over the long term, initial tensile results must also be linked separately to wet-state conditions, fatigue, fixation methods, and tissue integration.1
Gradually opening the support layer while retaining directional cues
Xie et al. (2024) combined a gradient-degradable woven layer composed of PGA and silk yarn with an electrospun layer providing directional guidance. The more rapidly degradable component gradually formed entry channels, while the electrospun layer provided cues for cell and collagen alignment at different stages. The study observed tissue infiltration and alignment in a rat Achilles tendon defect and conducted mechanical evaluation at 8 weeks, reporting improved repair.2
The insight from this animal study is to design “the structure at implantation” and “the structure after degradation” as a continuous process. Simply increasing initial porosity or nanofiber thickness may alter the balance between support and cell entry; thus, the entire composite scaffold must be observed over time.2
04Cartilage Repair: From Zonal Structures to Fiber-Reinforced Matrices
Forming distinct structural zones through process combinations
A UK team (Munir et al., 2019) combined low-temperature printing with electrospinning to construct a multi-zone PCL scaffold featuring different fiber orientations and pore structures. Mesenchymal stem cells adhered and survived during 4 weeks of in vitro culture, retaining glycosaminoglycan-related characteristics. The study supports exploring zonal structures as platforms for cartilage culture; it does not directly demonstrate that articular cartilage has already regained normal function in animals or patients.3
Short electrospun fibers can also serve as reinforcing components in three-dimensional scaffolds
Weiming Chen et al. (2020) reported treating gelatin/PLGA electrospun fibers as dispersed short fibers and incorporating them into cartilage decellularized-matrix printing ink. The resulting scaffold balanced predefined shape, internal pore structure, and wet-state mechanics, and reported improved repair in a rabbit articular cartilage defect. Here, electrospinning primarily provided reinforcing components; the final sample consisted of fibers, decellularized matrix, and subsequent shaping.4
Core-shell fibers introduce local release into cartilage cell studies
Wei Chen et al. (2020) used coaxial electrospinning to encapsulate glucosamine sulfate within PCL fibers, examining structural effects, release behavior, and the in vitro response of rat articular cartilage cells. The results support exploring this material’s ability to promote cell growth under specific culture conditions, but the evidence remains at the cellular level. Its research objective of “cartilage regeneration” cannot be directly stated as having already repaired cartilage defects.5
05Skeletal Muscle Research: Simultaneously Achieving Alignment and Cell Compatibility
A Korean team (Yeo and Kim, 2020) combined cell electrospinning with 3D printing, constructing alginate fibers containing human umbilical vein endothelial cells (HUVECs) on a PCL/ collagen support structure, followed by seeding and coculturing with C2C12 myoblasts. The study observed improvements in cell alignment, myotube-related morphology, and myogenic gene expression, linking fiber-directional cues with coordination among different cell types.6
This is an in vitro skeletal muscle tissue engineering platform. The involvement of endothelial cells in culture cannot be equated with having established perfusable vasculature, nor can myotube markers be used to infer restoration of muscle strength. Its significance for material development lies in proposing separately investigable variables: how the support structure is fixed, how fibers guide cells, which cell types are placed where, and how interactions are evaluated.6
Cell electrospinning also differs from a process in which cell-free fibers are first prepared and then seeded. The former requires specialized design around live-cell conditions, bioinks, and operational environments; process parameters from conventional solvent-based electrospinning cannot be directly transferred to live-cell systems.6
06From Structural Similarity to Tissue Function: Evidence Must Be Linked Gradually
These papers collectively demonstrate the design value of fiber orientation, zonation, and composites, but each addresses different questions. The fiber bundles of Pauly, the multi-zone cartilage scaffold of Munir, the glucosamine sulfate core-shell fibers, and the coculture platform of Yeo are primarily supported by materials or in vitro experiments; the Achilles tendon scaffold of Xie and the cartilage composite scaffold of Weiming Chen further conducted corresponding animal defect studies.1,2,3,4,5,6
The ordered collagen in tendons, glycosaminoglycans or type II collagen in cartilage, and myogenic markers in muscle all help clarify the repair process, but they cannot substitute for one another or independently represent long-term function. When interpreting results, the tissue site, animal species, evaluation period, and control conditions should be retained. The literature selected for this review does not provide human efficacy trials, and no assertion is made about whether other human studies exist in the field as a whole.1,2,3,4,5,6
07Translating Tissue Requirements into Samples That Can Be Fabricated and Tested
For tendons, orientation can first specify whether the sample is a planar patch, a wound fiber bundle, or a woven composite, as well as the primary load-bearing direction and fixation method. For cartilage, orientation can describe thickness, zonation, compressive requirements, and whether fibers are to be combined with hydrogels or decellularized matrix. For skeletal muscle culture, the starting point can be cell type, orientation, and culture support. Different information corresponds to different collection and composite configurations.
For oriented samples, the fiber orientation distribution and axial versus transverse differences should be recorded. For layered scaffolds, interlayer bonding and wet-state deformation should be examined. For short-fiber-reinforced systems, fiber dispersion, length distribution, and subsequent shaping should be evaluated together. When continuously fabricating or scaling up the area, it is also necessary to verify that similar structures are maintained across different locations, avoiding situations where averages mask local variations.
Residual solvents, cleaning, and sterilization effects must be assessed in conjunction with the material system. If proteins, drugs, or live cells are included, their corresponding activity and treatment tolerance must also be validated. Only by correlating process documentation, structural characterization, and biological evaluation can the sources of differences between samples be determined and equipment functionality discussed accordingly.1,2,3,4,5,6
08Common Issues in the Development of Tendons, Cartilage, and Muscle Scaffolds
Does Having Oriented Fibers Guarantee Tendon Regeneration?
Orientation is a valuable structural cue, but it must also be coordinated with cell entry, support retention, and tissue remodeling. In vitro results from planar membranes and the repair of a complete Achilles tendon defect represent different stages of evidence.1,2
Can Electrospinning Only Produce Thin Films?
No. The literature includes wound fiber bundles, three-dimensional scaffolds combined with woven or printed structures, and short fibers used as reinforcing components. The final morphology must be determined according to the intended application and linked to appropriate post-processing steps.1,2,3,4
Must Cartilage Scaffolds Use a Core-Shell Drug-Loading Structure?
Not necessarily. Zonal geometry, fiber reinforcement, and local release represent different research approaches. The priority should be clarifying whether the goal is to address cell distribution, wet-state support, or delivery of biological components, and then selecting a corresponding structure.3,4,5
References
The following are the original studies used in this review, independently summarized by TONGLI. The interpretation of the literature does not imply that the paper authors or research institutions have equipment procurement or cooperative relationships with TONGLI; the specific reading scope is described in each literature entry.
Bibliographic records retain the original publication language for accurate lookup.
Pauly HM, Kelly DJ, Popat KC, et al. Mechanical properties and cellular response of novel electrospun nanofibers for ligament tissue engineering: Effects of orientation and geometry. Journal of the Mechanical Behavior of Biomedical Materials. 2016;61:258–270.
DOI：10.1016/j.jmbbm.2016.03.022 ↗Scope of Review: Local original full text, with verification of PubMed and author-institution records
Xie X, Wang X, Ding D, et al. Multilayer woven scaffolds with gradient degradation and nano guidance properties for tendon reconstruction: Continuously promoting tissue infiltration and inducing tissue alignment. Nano Today. 2024;56:102277.
DOI：10.1016/j.nantod.2024.102277 ↗Scope of Review: Local original full text, with verification of the weaving/electrospinning methods, rat Achilles tendon model, and 8-week mechanical evaluation; journal page verification
Munir N, McDonald A, Callanan A. A combinatorial approach: Cryo-printing and electrospinning hybrid scaffolds for cartilage tissue engineering. Bioprinting. 2019;16:e00056.
DOI：10.1016/j.bprint.2019.e00056 ↗Scope of Review: Local original full text and journal abstract; the local file includes a supplementary correction to the 2020-year conflict-of-interest statement
Chen W, Xu Y, Li Y, et al. 3D printing electrospinning fiber-reinforced decellularized extracellular matrix for cartilage regeneration. Chemical Engineering Journal. 2020;382:122986.
DOI：10.1016/j.cej.2019.122986 ↗Scope of Review: Local original full text, with verification of the journal’s original abstract, methods, and conclusions
Chen W, Wang C, Gao Y, et al. Incorporating chitin derived glucosamine sulfate into nanofibers via coaxial electrospinning for cartilage regeneration. Carbohydrate Polymers. 2020;229:115544.
DOI：10.1016/j.carbpol.2019.115544 ↗Scope of review: local original full texts, with verification of PubMed against journal abstracts; for in vitro chondrocyte experiments
Yeo M, Kim G. Micro/nano-hierarchical scaffold fabricated using a cell electrospinning/3D printing process for co-culturing myoblasts and HUVECs to induce myoblast alignment and differentiation. Acta Biomaterialia. 2020;107:102–114.
DOI：10.1016/j.actbio.2020.02.042 ↗Scope of review: local original full texts and the PubMed abstract; for in vitro cell co-culture
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