Electrospun materials for ophthalmology and corneal repair: cell carriers, transparent structures, and research progress

01First, distinguish the material requirements of the limbal stroma and endothelium

Although both may be called corneal repair membranes, they can actually serve different functions. Carriers for the limbus and ocular surface focus on cell adhesion, spreading, and delivery; stromal scaffolds focus on organizing fibers and extracellular matrix; endothelial carriers must support a cell layer while considering permeability and handling. Clarifying the target tissue layer during early development can prevent applying results from one cell type to another application.^1,2,3,4,5,6

In these applications, electrospinning can either directly form a culture surface or serve as a reinforcing layer for another material. Membrane transparency, cell viability, and the restoration of visual function by an intact cornea represent distinct levels of assessment that require corresponding observation methods and cannot substitute for one another.

02What structural options for corneal materials does electrospinning provide?

Existing studies have constructed fibrous layers using collagen, gelatin, and degradable polymers, altered alignment through collector design, created microstructures using templates, or combined materials with native tissue matrices. The formulation and structure jointly determine the cell contact interface; the membrane's thickness, post-absorption morphology, and post-treatment also influence its eventual application.^1,2,3,4,5,6

Aligned fibers and microstructured templates address different questions

Aligned fibers primarily provide microscopic alignment cues, making them suitable for assessing whether cells and newly formed matrix organize along a specific direction. Templates with microgrooves or microcavities, by contrast, are used to define the spatial arrangement of cells. The two can be studied separately; not all structures need to be incorporated into the first batch of samples.^2,3

Transparency and wet-state stability must be designed together

Reducing thickness may alter handling robustness; adjusting fiber spacing may affect cell coverage and substance transport; crosslinking or blending may change post-absorption morphology. Therefore, a more meaningful comparison involves the final membrane after post-treatment and wetting under actual conditions, rather than merely the dry fibers immediately after collection.^5,6

03Corneal stromal research: from cell alignment to newly formed matrix organization

Phu et al. (2011) compared the behavior of rabbit-derived corneal fibroblasts on aligned versus nonaligned type I collagen fibers, while also examining α-SMA and light scattering associated with the myofibroblast phenotype. Under these in vitro conditions, the aligned scaffold group exhibited lower expression of relevant markers and reduced light scattering. The study indicates that evaluation should not be limited to cell numbers; phenotypic and optical characteristics can also be observed.¹

Wu et al. (2012) cultured human corneal stromal stem cells using aligned polyurethane urea (PEUU) fibers. Cells formed a more organized collagen matrix on the aligned substrates; cells on random fibers or flat membranes also formed matrices, but with different organizational patterns. This in vitro work extended the role of fiber alignment from cell morphology to the materials produced by cells.²

The two studies also highlight that culture conditions and substrate structures should be controlled separately. If aligned and random samples differ simultaneously in surface density or thickness, it becomes difficult to attribute all results solely to directional changes. During preliminary screening, flat membranes and random fiber controls can be retained, with variables such as interlayer angles gradually introduced.

04Corneal limbal cell carriers: from artificial microenvironments to composite membranes

In Ortega et al. (2013), a template with microstructures was first prepared using microstereolithography, followed by deposition of PLGA fibers to obtain a ring-shaped carrier featuring microcyst-like structures. Preliminary evaluation was conducted using rabbit limbal epithelial and stromal cells to attempt construction of an artificial microenvironment capable of accommodating cells. This constitutes a preparation and in vitro study; it does not demonstrate that the material can replace a complete cornea.³

In Zhou et al. (2019), a different approach was adopted: a PCL nanofiber mesh was interface-bonded with decellularized amnion to enhance the material’s mechanical properties and suture retention while preserving the biological functions of the amnion. In a rabbit model of limbal stem cell deficiency caused by alkali burns, the composite membrane supported cell transplantation, and improvements related to re-epithelialization, inflammation, and neovascularization were observed. These repair outcomes represent in vivo animal evidence.⁴

These two approaches correspond to different development starting points: teams with existing cell culture workflows can study templates and cell distribution; teams with existing natural membrane materials can study fiber-reinforced layers and interfacial bonding. The latter group must particularly distinguish between operational improvements resulting from reinforcement and repair effects produced by the cells, avoiding attribution of the entire composite system’s effects to the electrospun layer.

05Why does wet-state stability become a critical issue for corneal carriers?

In Villanueva Navarrete et al. (2026), the integrity and handling of PLGA carriers after wetting were addressed by comparing different PLGA/PCL compositions. Within the systems tested in the paper, a formulation containing 30% PCL better maintained its mechanical performance in both dry and wet states and supported outward cell growth from human and porcine limbal tissue explants. This involves tissue explant culture and material testing; the use of human-derived tissue does not imply that patient transplantation has been performed.⁶

This study concretely identified a problem that is easily overlooked in microscopic images: although cells can grow on a membrane, difficult handling of the membrane after transfer, spreading, or wetting can still limit the carrier’s usability. This composition represents a result obtained under the specified material specifications and experimental conditions; it is not a fixed formula that should be adopted for all PLGA/PCL corneal membrane sheets.⁶

06Endothelial cell carriers: thin films must consider both light transmission and delivery

Song et al. (2024) electrospun gelatin into a nanofiber membrane, then crosslinked it, studying its light transmission, mechanical properties, permeability, and degradation behavior. The authors cultured human and rabbit corneal endothelial cells, observed cell junctions and function-related markers, and conducted delivery and adhesion experiments in fresh enucleated rabbit eyes. The paper demonstrates the feasibility of the membrane as an endothelial cell carrier, but it does not constitute a long-term in vivo efficacy study or a human vision improvement study.⁵

The design objectives of endothelial carriers differ from those of ocular surface coverage membranes: they require coordination among thin-film handling, cell layer retention, and substance exchange. If subsequent evaluation aims to determine whether the cornea’s water-regulation function is restored, corresponding functional tests and disease models are also required; conclusions cannot be drawn solely from marker expression. The studies selected in this paper are insufficient to establish human efficacy conclusions for these electrospun corneal materials.

For ophthalmic material development, the value of ex vivo experiments lies in subjecting culture membranes to spatial and operational testing closer to actual delivery. Compared with simple culture, they answer additional questions but still lack long-term degradation, inflammatory responses, and tissue interactions in vivo; this stage limitation should be acknowledged when reading the work.

07From literature protocols to reproducible ophthalmic fibrous membrane samples

First, define the tasks for the cells and the membrane

Begin by clarifying whether the goal is a culture substrate, a cell-delivery membrane, or a tissue repair scaffold. Then specify the cell type, culture duration, membrane dimensions, and final transfer method. Different objectives influence trade-offs among thickness, degradation, and transparency, and also determine whether a ring-shaped, aligned, or multilayer collection structure is required.

Compare optical and structural properties under identical conditions

Light transmission tests should record sample thickness, dry or wet state, detection wavelength range, and reference standards; when necessary, distinguish between light transmission and light scattering. For samples containing cells, the contributions of the membrane itself versus the cells or newly formed matrix should also be differentiated. A light transmission value reported in the literature cannot be directly converted into a product target without these conditions.^1,5

Link postprocessing to the final sample

Crosslinking, cleaning, drying, and sterilization may alter membrane structure and cell-contact interfaces. Each step can be recorded alongside final thickness, wet-state dimensions, and cell evaluations, with residual substances and biocompatibility verified for the specific material system. After increasing the preparation area, uniformity across the effective region and integrity after cutting must also be checked.

Equipment discussions can focus on stable fluid supply, thin-film deposition, aligned collection, template compatibility, and environmental control. The more specific the sample requirements, the easier it becomes to determine whether electrospinning is responsible for an independent membrane, a reinforcing layer on a natural substrate, or a component within a composite tissue structure.

08Common issues in ophthalmic electrospun material development

Can an electrospun membrane be used for corneal transplantation simply because it supports corneal cell culture?

Cell culture demonstrates compatibility and growth under specific conditions. Delivery, post-implantation responses, and functional recovery require validation at different stages. The matrix culture, ex vivo endothelial delivery, and rabbit ocular surface repair described in this paper address distinct questions, respectively.^2,4,5

Do ophthalmic materials necessarily need to be completely transparent over their entire area?

This should be judged based on the intended placement and function. The design requirements for corneal stroma replacement, ring-shaped limbal carriers, and short-term cell-delivery membranes are not identical. Defining the optical region, retention time, and target function before setting optical evaluation criteria is more meaningful than simply pursuing a transparent appearance for the thin film.^1,2,3,5

Can existing natural membrane materials still be combined with electrospinning?

Fibers can be studied as reinforcing or cell-contact layers. The work involving composite amniotic membrane provides an example, but it is necessary to verify that interfacial bonding, wet-state handling, and biological functions are retained, rather than merely combining two materials.⁴

References

The following are the original studies used in this document. Literature [1,3,5,6] was cross-read with relevant chapters of the full text, and [2,4] was compiled based on the original abstracts and bibliographic information. The study interpretations do not indicate that the paper authors or institutions have any equipment procurement or cooperative relationships with TONGLI.

Bibliographic records retain the original publication language for accurate lookup.

1. Phu D, Wray LS, Warren RV, et al. Effect of Substrate Composition and Alignment on Corneal Cell Phenotype. Tissue Engineering Part A. 2011;17(5–6):799–807.

   DOI：10.1089/ten.tea.2009.0724 ↗

   Scope of review: Original full-text abstracts, methods, and results chapters of PMC

2. Wu J, Du Y, Watkins SC, et al. The engineering of organized human corneal tissue through the spatial guidance of corneal stromal stem cells. Biomaterials. 2012;33(5):1343–1352.

   DOI：10.1016/j.biomaterials.2011.10.055 ↗

   Scope of review: Original abstracts and author-institution literature records of PubMed

3. Ortega Í, Ryan AJ, Deshpande P, et al. Combined microfabrication and electrospinning to produce 3-D architectures for corneal repair. Acta Biomaterialia. 2013;9:5511–5520.

   DOI：10.1016/j.actbio.2012.10.039 ↗

   Scope of review: Local original full-text abstracts, preparation methods, and conclusions

4. Zhou Z, Long D, Hsu CC, et al. Nanofiber-reinforced decellularized amniotic membrane improves limbal stem cell transplantation in a rabbit model of corneal epithelial defect. Acta Biomaterialia. 2019;97:310–320.

   DOI：10.1016/j.actbio.2019.08.027 ↗

   Scope of review: Original abstracts and bibliographic information of PubMed

5. Song E, Chen KM, Margolis MS, et al. Electrospun Nanofiber Membrane for Cultured Corneal Endothelial Cell Transplantation. Bioengineering. 2024;11(1):54.

   DOI：10.3390/bioengineering11010054 ↗

   Scope of review: Original abstracts and publicly available full-text introductions, methods, and conclusions; verified as experiments from ex vivo

6. Villanueva Navarrete D, Sandoval-Castellanos AM, Gunen M, et al. Wet-stable PLGA–PCL electrospun membranes as synthetic scaffolds for corneal applications. Biomedical Materials. 2026;21(2):025033.

   DOI：10.1088/1748-605X/ae57f1 ↗

   Scope of review: Official full-text abstracts, methods, results, and conclusions archived by the author institutions