Assembly and Application of a Three‐Dimensional Human Corneal Tissue Model

McKay, Tina B.; Ford, Andrew; Wang, Siran; Cairns, Dana M.; Parker, Rachael N.; Deardorff, Phillip; Ghezzi, Chiara E.; Kaplan, David L.

doi:10.1002/cptx.84

Cited by 11 publications

(7 citation statements)

References 34 publications

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“…Alternatively, ongoing work to generate tissue mimics for in vitro analysis of cell responses to pharmaceuticals or therapeutics is making great strides. Bioreactors enabling air liquid interface culture, as well as multilayer mimics [ 111 , 173 ], allow for exploration of hypotheses related to cell-cell interaction, protein production and paracrine signaling. Overall, innovations and advances in recent years highlight the complexity in translating exciting and promising technology from the laboratory to the clinic.…”

Section: Discussionmentioning

confidence: 99%

Recent Advances in Natural Materials for Corneal Tissue Engineering

et al. 2021

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Given the incidence of corneal dysfunctions and diseases worldwide and the limited availability of healthy, human donors, investigators are working to generate engineered cellular and acellular therapeutic approaches as alternatives to corneal transplants from human cadavers. These engineered strategies aim to address existing complications with human corneal transplants, including graft rejection, infection, and complications resulting from surgical methodologies. The main goals of these research endeavors are to (1) determine ideal mechanical properties, (2) devise methodologies to improve the efficacy of engineered corneal grafts and cell-based therapies, and (3) optimize transplantation of engineered tissue structures in the eye. Thus, recent innovations have sought to address these challenges through both in vitro and in vivo studies. This review covers recent work aimed at evaluating engineered materials, potential therapeutic cells, and the resulting cell-material interactions that lead to optimal corneal graft properties. Furthermore, we discuss promising strategies in corneal tissue engineering techniques and in vivo studies in animal models.

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Section: Discussionmentioning

confidence: 99%

Recent Advances in Natural Materials for Corneal Tissue Engineering

et al. 2021

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“…Silk protein was chosen because of its structural and mechanical properties and inertness. Silk is a versatile, biocompatible, and biodegradable material with tunable mechanical properties and is extensively used in tissue engineering for mimicking soft and high-strength human tissues [23][24][25][26] . In our model, silk was used in a sponge format to replicate the soft architecture of the nasal tissue with a controlled pore size.…”

Section: Discussionmentioning

confidence: 99%

In VitroNasal Tissue Model for the Validation of Nasopharyngeal and Mid-turbinate Swabs for SARS-CoV-2 Testing

Hartigan

Adelfio

Shutt

et al. 2021

Preprint

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Large-scale population testing is a key tool to mitigate the spread of respiratory pathogens, as in the current COVID-19 pandemic, where swabs are used to collect samples in the upper airways (e.g. nasopharyngeal and mid-turbinate nasal cavities) for diagnostics. However, the high volume of supplies required to achieve large-scale population testing has posed unprecedented challenges for swab manufacturing and distribution, resulting in a global shortage that has heavily impacted testing capacity world-wide and prompted the development of new swabs suitable for large-scale production. Newly designed swabs require rigorous pre-clinical and clinical validation studies that are costly and time consuming (i.e. months to years long); reducing the risks associated with swab validation is therefore paramount for their rapid deployment. To address these shortages, we developed a 3D-printed tissue model that mimics the nasopharyngeal and mid-turbinate nasal cavities, and we validated its use as a new tool to rapidly test swab performance. In addition to the nasal architecture, the tissue model mimics the soft nasal tissue with a silk-based sponge lining, and the physiological nasal fluid with asymptomatic and symptomatic viscosities of synthetic mucus. We performed several assays comparing standard flocked and injection-molded swabs. We quantified the swab pick-up and release, and determined the effect of viral load and mucus viscosity on swab efficacy by spiking the synthetic mucus with heat-inactivated SARS-CoV-2 virus. By molecular assays, we found that injected molded swabs performed similarly or superiorly in comparison to standard flocked swabs and we underscored a viscosity-dependent difference in cycle threshold values between the asymptomatic and symptomatic mucus for both swabs. To conclude, we developed an in vitro nasal tissue model, that corroborated previous swab performance data from clinical studies, with the potential of providing researchers with a clinically relevant, reproducible, safe, and cost-effective validation tool for the rapid development of newly designed swabs.

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“…Their advantage is that cells are extracted from tissues or from biopsies and seeded on semipermeable membranes after few passages [ 57 , 58 ]. In the appropriate cell culture media with growth factors and other supplements, the cells differentiate and acquire some organotypic phenotype, wherein cell-cell or cell-matrix interactions can be studied, as well as pathogenesis of e.g., viral infection [ 54 , 57 , 58 , 59 , 60 , 61 , 62 , 63 ]. Therefore, the following sections first describe the current 3D models for each compartment individually.…”

Section: Development Of 3d Cell Culture Modelsmentioning

confidence: 99%

The Communication between Ocular Surface and Nasal Epithelia in 3D Cell Culture Technology for Translational Research: A Narrative Review

Aydin

Dietrich

Witt

et al. 2021

IJMS

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There is a lack of knowledge regarding the connection between the ocular and nasal epithelia. This narrative review focuses on conjunctival, corneal, ultrastructural corneal stroma, and nasal epithelia as well as an introduction into their interconnections. We describe in detail the morphology and physiology of the ocular surface, the nasolacrimal ducts, and the nasal cavity. This knowledge provides a basis for functional studies and the development of relevant cell culture models that can be used to investigate the pathogenesis of diseases related to these complex structures. Moreover, we also provide a state-of-the-art overview regarding the development of 3D culture models, which allow for addressing research questions in models resembling the in vivo situation. In particular, we give an overview of the current developments of corneal 3D and organoid models, as well as 3D cell culture models of epithelia with goblet cells (conjunctiva and nasal cavity). The benefits and shortcomings of these cell culture models are discussed. As examples for pathogens related to ocular and nasal epithelia, we discuss infections caused by adenovirus and measles virus. In addition to pathogens, also external triggers such as allergens can cause rhinoconjunctivitis. These diseases exemplify the interconnections between the ocular surface and nasal epithelia in a molecular and clinical context. With a final translational section on optical coherence tomography (OCT), we provide an overview about the applicability of this technique in basic research and clinical ophthalmology. The techniques presented herein will be instrumental in further elucidating the functional interrelations and crosstalk between ocular and nasal epithelia.

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Assembly and Application of a Three‐Dimensional Human Corneal Tissue Model

Cited by 11 publications

References 34 publications

Recent Advances in Natural Materials for Corneal Tissue Engineering

Recent Advances in Natural Materials for Corneal Tissue Engineering

In VitroNasal Tissue Model for the Validation of Nasopharyngeal and Mid-turbinate Swabs for SARS-CoV-2 Testing

The Communication between Ocular Surface and Nasal Epithelia in 3D Cell Culture Technology for Translational Research: A Narrative Review

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