Mechanobiology of the corneal epithelium

Masterton, Sophia; Ahearne, Mark

doi:10.1016/j.exer.2018.08.001

Cited by 60 publications

(57 citation statements)

References 107 publications

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“…The scaffolds must be sufficiently stiff and strong to be able to withstand suturing without tearing and withstand physiological forces applied to it postimplantation such as intraocular pressure, eyelid motion, and tear film motion. [44] If the scaffold is insufficiently stiff or strong, it could undergo deformation or failure, respectively. The scaffold stiffness should also not be too high, as this would reduce its ability to deform in the same way as the surrounding tissue when under stress and potentially lead to a mismatch in strain.…”

Section: Scaffold Physical Propertiesmentioning

confidence: 99%

Designing Scaffolds for Corneal Regeneration

Ahearne

Fernández‐Pérez

Masterton

et al. 2020

Adv Funct Materials

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121

109

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Corneal blindness is one of the most common causes of vision loss worldwide, affecting millions of people. To treat these patients, researchers have been examining different approaches to engineer corneal scaffolds suitable for transplantation. Scaffolds have been developed to replace part or all of the cornea depending on the patient requirements. Both acellular and cell-seeded scaffolds have been tested in animal models. Materials that have been under investigation for manufacturing scaffolds include collagen, silk fibroin, amniotic membrane, decellularized cornea, fibrin, chitosan, gelatin, agarose, alginate, and hyaluronic acid in addition to several synthetic polymers. Different combinations of materials, fiber crosslinking techniques, and incorporation of bioactive molecules have also been examined. Factors such as the physical properties, cytocompatibility, degradation behavior, and optical characteristics have to be considered when selecting a suitable scaffold material. Recent advancements in materials fabrication techniques such as bioprinting, electrospinning, and different collagen alignment techniques, allow scaffolds to be generated that more accurately mimic the structure of the corneal stroma. A number of scaffolds have commenced clinical trials to determine their suitability for corneal regeneration.

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Section: Scaffold Physical Propertiesmentioning

confidence: 99%

Designing Scaffolds for Corneal Regeneration

Ahearne

Fernández‐Pérez

Masterton

et al. 2020

Adv Funct Materials

Self Cite

121

109

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show abstract

“…The role of tissue biomechanics in corneal function, and in particular as a regulator of LESC behavior, has been the focus of growing research in the past decade. 49 Studies using contact 50 and non-contact 51 analytical tools have demonstrated that the corneal limbus represents a biomechanical niche distinct from its central region. Specifically, the high-resolution characterization of corneal biomechanics shows that the matrix supporting epithelial cells in the limbus is significantly more heterogeneous compared with that supporting the central epithelium, and is comprised of numerous pockets with significantly lower elastic modulus associated with LESC residency.…”

Section: Corneal Biomechanics In Health and Diseasementioning

confidence: 99%

Biomechanical Modulation Therapy—A Stem Cell Therapy Without Stem Cells for the Treatment of Severe Ocular Burns

Gouveia

Connon

2020

Trans. Vis. Sci. Tech.

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Ocular injuries caused by chemical and thermal burns are often unmanageable and frequently result in disfigurement, corneal haze/opacification, and vision loss. Currently, a considerable number of surgical and pharmacological approaches are available to treat such injuries at either an acute or a chronic stage. However, these existing interventions are mainly directed at (and limited to) suppressing corneal inflammation and neovascularization while promoting re-epithelialization. Reconstruction of the ocular surface represents a suitable but last-option recourse in cases where epithelial healing is severely impaired, such as due to limbal stem cell deficiency. In this concise review, we discuss how biomechanical modulation therapy (BMT) may represent a more effective approach to promoting the regeneration of ocular tissues affected by burn injuries via restoration of the limbal stem cell niche. Specifically, the scientific basis supporting this new therapeutic modality is described, along with our growing understanding of the role that tissue biomechanics plays in stem cell fate and function. The potential impact of BMT as a future treatment option for the management of injuries affecting tissue compliance is also further discussed.

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“…Moreover, epithelial stem cell therapies have largely ignored the niche and focused on cell populations to be transplanted, and this neglect leads to a lack of control over stem cell behavior that may contribute to the high failure rates of cell therapies. [ 8–10 ] In addition to mechanical cues, we hypothesized that spatial geometry plays a crucial role in determining stem cell fate. Our aim was to recreate the precise geometry of an epithelial stem cell niche using two‐photon polymerization (2PP) and to determine the role of spatial geometry on stem cell phenotype in a 3D microniche setting.…”

Section: Figurementioning

confidence: 99%

Bioinspired Precision Engineering of Three‐Dimensional Epithelial Stem Cell Microniches

et al. 2020

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Maintenance of the epithelium relies on stem cells residing within specialized microenvironments, known as epithelial crypts. Two‐photon polymerization (2PP) is a valuable tool for fabricating 3D micro/nanostructures for stem cell niche engineering applications. Herein, biomimetic gelatin methacrylate‐based constructs, replicating the precise geometry of the limbal epithelial crypt structures (limbal stem cell “microniches”) as an exemplar epithelial niche, are fabricated using 2PP. Human limbal epithelial stem cells (hLESCs) are seeded within the microniches in xeno‐free conditions to investigate their ability to repopulate the crypts and the expression of various differentiation markers. Cell proliferation and a zonation in cell phenotype along the z‐axis are observed without the use of exogenous signaling molecules. Significant differences in cell phenotype between cells located at the base of the microniche and those situated towards the rim are observed, demonstrating that stem cell fate is strongly influenced by its location within a niche and the geometrical details of where it resides. This study provides insight into the influence of the niche’s spatial geometry on hLESCs and demonstrates a flexible approach for the fabrication of biomimetic crypt‐like structures in epithelial tissues. This has significant implications for regenerative medicine applications and can ultimately lead to implantable synthetic “niche‐based” treatments.

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Mechanobiology of the corneal epithelium

Cited by 60 publications

References 107 publications

Designing Scaffolds for Corneal Regeneration

Designing Scaffolds for Corneal Regeneration

Biomechanical Modulation Therapy—A Stem Cell Therapy Without Stem Cells for the Treatment of Severe Ocular Burns

Bioinspired Precision Engineering of Three‐Dimensional Epithelial Stem Cell Microniches

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