Corneal endothelium tissue engineering: An evolution of signaling molecules, cells, and scaffolds toward 3D bioprinting and cell sheets

Khalili, Mostafa; Asadi, Maryam; Kahroba, Houman; Soleyman, Mohammad Reza; André, Helder

doi:10.1002/jcp.30085

Cited by 25 publications

(22 citation statements)

References 268 publications

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“…Typically, a 3D image of the cornea is created via ultrasound or optical coherence tomography (OCT), though a Scheimpflug camera can be used as well [ 12 , 17 ]. The ideal printing medium, referred to as “bioink,” must have the mechanical strength to withstand the shear stress of extrusion through the nozzle, retain adequate transparency, support cell viability, allow diffusion of nutrients and oxygen, be suturable, and be biodegradable [ 1 , 14 ]. They often must be cross-linked to maintain their structure [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

“…They often must be cross-linked to maintain their structure [ 18 ]. Optics is one of the biggest challenges, as the process requires sufficiently high resolution for a smooth surface and involves printing flat layers into a curved structure [ 1 ]. Multiple authors have described promising results in meeting the above parameters, but the ultimate challenge remains in building toward a multilayered and fully replicative structure [ 19 ].…”

Section: Methodsmentioning

confidence: 99%

“…A range of methods have emerged based on various layering techniques and printing materials. These include fused deposition modeling (FDM), inkjet, stereolithography, and microvalve-based and laser-assisted printing [ 1 ]. The technology enables custom-designed products to be created faster, more economically, and more locally than by traditional manufacturing.…”

Section: Introductionmentioning

confidence: 99%

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3D Printing in Eye Care

2021

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Three-dimensional printing enables precise modeling of anatomical structures and has been employed in a broad range of applications across medicine. Its earliest use in eye care included orbital models for training and surgical planning, which have subsequently enabled the design of custom-fit prostheses in oculoplastic surgery. It has evolved to include the production of surgical instruments, diagnostic tools, spectacles, and devices for delivery of drug and radiation therapy. During the COVID-19 pandemic, increased demand for personal protective equipment and supply chain shortages inspired many institutions to 3D-print their own eye protection. Cataract surgery, the most common procedure performed worldwide, may someday make use of custom-printed intraocular lenses. Perhaps its most alluring potential resides in the possibility of printing tissues at a cellular level to address unmet needs in the world of corneal and retinal diseases. Early models toward this end have shown promise for engineering tissues which, while not quite ready for transplantation, can serve as a useful model for in vitro disease and therapeutic research. As more institutions incorporate in-house or outsourced 3D printing for research models and clinical care, ethical and regulatory concerns will become a greater consideration. This report highlights the uses of 3D printing in eye care by subspecialty and clinical modality, with an aim to provide a useful entry point for anyone seeking to engage with the technology in their area of interest.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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3D Printing in Eye Care

2021

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“…Furthermore, one of the future challenges lies in designing tissue substitutes that provide the characteristics of the Descemet's membrane (DM), as studies have shown that the DM is crucial as a substrate in damaged corneal endothelium (CE) regeneration [127]. This has led to researchers bioengineering constructs that are able mimic the DM properties such as (i) physiochemical properties, (ii) 3D architecture and (iii) mechanical properties in order to facilitate the support of functional corneal endothelium as that in the in vivo cornea [78].…”

Section: Endotheliummentioning

confidence: 99%

Biofabrication of Artificial Stem Cell Niches in the Anterior Ocular Segment

et al. 2021

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The anterior segment of the eye is a complex set of structures that collectively act to maintain the integrity of the globe and direct light towards the posteriorly located retina. The eye is exposed to numerous physical and environmental insults such as infection, UV radiation, physical or chemical injuries. Loss of transparency to the cornea or lens (cataract) and dysfunctional regulation of intra ocular pressure (glaucoma) are leading causes of worldwide blindness. Whilst traditional therapeutic approaches can improve vision, their effect often fails to control the multiple pathological events that lead to long-term vision loss. Regenerative medicine approaches in the eye have already had success with ocular stem cell therapy and ex vivo production of cornea and conjunctival tissue for transplant recovering patients’ vision. However, advancements are required to increase the efficacy of these as well as develop other ocular cell therapies. One of the most important challenges that determines the success of regenerative approaches is the preservation of the stem cell properties during expansion culture in vitro. To achieve this, the environment must provide the physical, chemical and biological factors that ensure the maintenance of their undifferentiated state, as well as their proliferative capacity. This is likely to be accomplished by replicating the natural stem cell niche in vitro. Due to the complex nature of the cell microenvironment, the creation of such artificial niches requires the use of bioengineering techniques which can replicate the physico-chemical properties and the dynamic cell–extracellular matrix interactions that maintain the stem cell phenotype. This review discusses the progress made in the replication of stem cell niches from the anterior ocular segment by using bioengineering approaches and their therapeutic implications.

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“…Most of the current culture media formulations for CEC expansion contain xenogeneic components, such as animal serum, which makes such media incompatible with strict clinical requirements. This problem can be partially solved by the substitution of animal serum with human serum [ 75 ], modified platelet lysate [ 76 ], or other recombinant proteins and small-molecule compounds [ 77 ] that have recently been used for CE ex vivo expansion.…”

Section: In Vitro Expansion Of Cells From Donor Tissuementioning

confidence: 99%

Ex vivo expansion and characterization of human corneal endothelium for transplantation: a review

2021

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The corneal endothelium plays a key role in maintaining corneal transparency. Its dysfunction is currently treated with penetrating or lamellar keratoplasty. Advanced cell therapy methods seek to address the persistent global deficiency of donor corneas by enabling the renewal of the endothelial monolayer with tissue-engineered grafts. This review provides an overview of recently published literature on the preparation of endothelial grafts for transplantation derived from cadaveric corneas that have developed over the last decade (2010–2021). Factors such as the most suitable donor parameters, culture substrates and media, endothelial graft storage conditions, and transplantation methods are discussed. Despite efforts to utilize alternative cellular sources, such as induced pluripotent cells, cadaveric corneas appear to be the best source of cells for graft preparation to date. However, native endothelial cells have a limited natural proliferative capacity, and they often undergo rapid phenotype changes in ex vivo culture. This is the main reason why no culture protocol for a clinical-grade endothelial graft prepared from cadaveric corneas has been standardized so far. Currently, the most established ex vivo culture protocol involves the peel-and-digest method of cell isolation and cell culture by the dual media method, including the repeated alternation of high and low mitogenic conditions. Culture media are enriched by additional substances, such as signaling pathway (Rho-associated protein kinase, TGF-β, etc.) inhibitors, to stimulate proliferation and inhibit unwanted morphological changes, particularly the endothelial-to-mesenchymal transition. To date, this promising approach has led to the development of endothelial grafts for the first in-human clinical trial in Japan. In addition to the lack of a standard culture protocol, endothelial-specific markers are still missing to confirm the endothelial phenotype in a graft ready for clinical use. Because the corneal endothelium appears to comprise phenotypically heterogeneous populations of cells, the genomic and proteomic expression of recently proposed endothelial-specific markers, such as Cadherin-2, CD166, or SLC4A11, must be confirmed by additional studies. The preparation of endothelial grafts is still challenging today, but advances in tissue engineering and surgery over the past decade hold promise for the successful treatment of endothelial dysfunctions in more patients worldwide.

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Corneal endothelium tissue engineering: An evolution of signaling molecules, cells, and scaffolds toward 3D bioprinting and cell sheets

Cited by 25 publications

References 268 publications

3D Printing in Eye Care

3D Printing in Eye Care

Biofabrication of Artificial Stem Cell Niches in the Anterior Ocular Segment

Ex vivo expansion and characterization of human corneal endothelium for transplantation: a review

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