ArticlePloS one2017
3D Functional Corneal Stromal Tissue Equivalent Based on Corneal Stromal Stem Cells and Multi-Layered Silk Film Architecture.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Keratocyte Gene Expression Shaped by ECM Dimensionality: Evidence for Enhanced Quiescence in 3D Culture.Bioengineering (Basel, Switzerland) · 2026Article
- Seeing through collagen: integrative pro-regenerative corneal implants for clearer future.NPJ Regenerative medicine · 2026Review
- Bioinspired Tissue Transparency: Achieving Sclera-to-Cornea Transplantation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- A Bioengineered Model of the Human Cornea for Preclinical Assessment of Human Ocular Exposure to Environmental Toxicants.Advanced healthcare materials · 2025Article
- Lentiviral Vector-MediatedHuman gene therapy · 2024Article
- Dimensionality Matters: Exploiting UV-Photopatterned 2D and Two-Photon-Printed 2.5D Contact Guidance Cues to Control Corneal Fibroblast Behavior and Collagen Deposition.Bioengineering (Basel, Switzerland) · 2024Article
- Regenerative Therapy for Corneal Scarring Disorders.Biomedicines · 2024Review
- Current microfluidic platforms for reverse engineering of cornea.Materials today. Bio · 2023Review
- Micropattern Silk Fibroin Film Facilitates Tendon RepairStem cells international · 2023Article
- Alginate-Based Composites for Corneal Regeneration: The Optimization of a Biomaterial to Overcome Its Limits.Gels (Basel, Switzerland) · 2022Review
- Preclinical Validation of a Novel Injection-Molded Swab for the Molecular Assay Detection of SARS-CoV-2.Diagnostics (Basel, Switzerland) · 2022Article
- Fiber-Based Biopolymer Processing as a Route toward Sustainability.Advanced materials (Deerfield Beach, Fla.) · 2022Review
- Tissue Models forFrontiers in cellular and infection microbiology · 2022Review
- Recent Advances in Natural Materials for Corneal Tissue Engineering.Bioengineering (Basel, Switzerland) · 2021Review
- Mechanical Properties of Bioengineered Corneal Stroma.Advanced healthcare materials · 2021Review
- Current perspectives of limbal-derived stem cells and its application in ocular surface regeneration and limbal stem cell transplantation.Stem cells translational medicine · 2021Review
- Silk Film Stiffness Modulates Corneal Epithelial Cell Mechanosignaling.Macromolecular chemistry and physics · 2021Article
- The Human Tissue-Engineered Cornea (hTEC): Recent Progress.International journal of molecular sciences · 2021Review
- The anti-scarring effect of corneal stromal stem cell therapy is mediated by transforming growth factor β3.Eye and vision (London, England) · 2020Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
The worldwide need for human cornea equivalents continues to grow. Few clinical options are limited to allogenic and synthetic material replacements. We hypothesized that tissue engineered human cornea systems based on mechanically robust, patterned, porous, thin, optically clear silk protein films, in combination with human corneal stromal stem cells (hCSSCs), would generate 3D functional corneal stroma tissue equivalents, in comparison to previously developed 2D approaches. Silk film contact guidance was used to control the alignment and distribution of hCSSCs on RGD-treated single porous silk films, which were then stacked in an orthogonally, multi-layered architecture and cultured for 9 weeks. These systems were compared similar systems generated with human corneal fibroblasts (hCFs). Both cell types were viable and preferentially aligned along the biomaterial patterns for up to 9 weeks in culture. H&E histological sections showed that the systems seeded with the hCSSCs displayed ECM production throughout the entire thickness of the constructs. In addition, the ECM proteins tested positive for keratocyte-specific tissue markers, including keratan sulfate, lumican, and keratocan. The quantification of hCSSC gene expression of keratocyte-tissue markers, including keratocan, lumican, human aldehyde dehydrogenase 3A1 (ALDH3A1), prostaglandin D2 synthase (PTDGS), and pyruvate dehydrogenase kinase, isozyme 4 (PDK4), within the 3D tissue systems demonstrated upregulation when compared to 2D single silk films and to the systems generated with the hCFs. Furthermore, the production of ECM from the hCSSC seeded systems and subsequent remodeling of the initial matrix significantly improved cohesiveness and mechanical performance of the constructs, while maintaining transparency after 9 weeks.
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