Print me a cornea - Are we there yet?

Thomas, Midhun Ben; Selvam, Shivaram; Agrawal, Parinita; Bellur, Prayag; Waghmare, Neha; Chowdhury, Suvro K.; Selvakumar, Kamalnath; Singh, Aastha; Tiwari, Anil; Gour, Abha; Sangwan, Virender S; Bhowmick, Tuhin; Chandru, Arun

doi:10.1016/j.bprint.2022.e00227

Cited by 4 publications

(3 citation statements)

References 74 publications

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“…To tackle the current tissue shortage and the limitations for the in vitro expansion of primary CEnCs, the de novo generation of CEnCs from hPSCs or other cell sources is needed in addition to the advanced and standardized cell and tissue production methods for clinical applications. In this concept, both the novel source of CEnCs from hPSCs [15][16][17][20][21][22][23][24] and 3D bioprinting of partial or full thickness corneal equivalent including all three cell layers (endothelium, stroma and epithelium) would be the holy grail in corneal tissue engineering and regenerative medicine [32]. Various studies have used 3D bioprinting for corneal tissue, concentrating mainly on stroma and epithelium, but corneal endothelium has received less attention [8][9][10].…”

Section: Discussionmentioning

confidence: 99%

Bioprinting of human pluripotent stem cell derived corneal endothelial cells with hydrazone crosslinked hyaluronic acid bioink

Grönroos,

Mörö,

Puistola

et al. 2023

Preprint

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Background: Human corneal endothelial cells lack regenerative capacity through cell division in vivo. Thus, in the case of trauma or dystrophy, the only treatment modality currently available is corneal tissue or primary corneal endothelial cell transplantation from cadaveric donor with high global shortage. Our ultimate goal is to use the state-of-the-art 3D-bioprint technology for automated production of human partial and full-thickness corneal tissues using human stem cells and functional bioinks. Here, we explored the possibility to bioprint corneal endothelium using human pluripotent stem cell derived corneal endothelial cells and hydrazone crosslinked hyaluronic acid bioink. Methods: Corneal endothelial cells differentiated from human pluripotent stem cells were bioprinted using optimized hydrazone crosslinked hyaluronic acid based bioink. Before bioprinting, the biocompatibility of the bioink with cells was first analyzed with transplantation on ex vivo denuded porcine corneas and on denuded human Descemet membrane. Then bioprinting was proceeded and the viability of human pluripotent stem cell derived corneal endothelial cells after bioprinting was verified with live/dead stainings. Histological and immunofluorescence stainings with ZO1, Na+/K+-ATPase and CD166 were used to confirm corneal endothelial cell phenotype in all experiments and STEM121 marker was used to identify human cells from the ex vivo porcine corneas. Results: The bioink modified for human pluripotent stem cell derived corneal endothelial cells successfully supported the viability and printability of the cells. After 10 days of ex vivo transplantations, STEM121 positive cells were verified on the Descemet membrane of porcine cornea showing the biocompatibility of the bioink. Furthermore, biocompatibility was confirmed on denuded human Descemet membrane showing corneal endothelial like characteristics. Seven days after bioprinting, the corneal endothelial like cells were viable and showed polygonal morphology with expression and native-like localization of ZO-1, Na+/K+-ATPase and CD166. Nevertheless, mesenchymal-like cells in some parts of the cultures were evident and those cells spread underneath the corneal endothelial-like cell layer. Conclusions: Our results demonstrate that human pluripotent stem cell derived corneal endothelial cells can be bioprinted in covalently crosslinked hyaluronic acid bioink. This approach has potential as a corneal endothelium transplant and furthermore, can be used in the mission of bioprinting the full-thickness human cornea.

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Section: Discussionmentioning

confidence: 99%

Bioprinting of human pluripotent stem cell derived corneal endothelial cells with hydrazone crosslinked hyaluronic acid bioink

Grönroos,

Mörö,

Puistola

et al. 2023

Preprint

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“…The cornea, which serves as the outermost layer of transparent and protective soft tissue in the eye, possesses a hierarchically oriented structure that facilitates the transmission and refraction of light to the retina 17 , 391 . Comprised mainly of type I collagen, the cornea is divided into three components: the epithelium, stroma, and endothelium 392 . Each component consists of oriented collagen fibers embedded within a hydrated proteoglycan rich gel matrix, which provides support for the fibrillar collagen structure.…”

Section: Effect Of Highly Oriented Structures On Cell Behaviorsmentioning

confidence: 99%

Highly oriented hydrogels for tissue regeneration: design strategies, cellular mechanisms, and biomedical applications

Wu,

Yun,

Song

et al. 2024

Theranostics

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Many human tissues exhibit a highly oriented architecture that confers them with distinct mechanical properties, enabling adaptation to diverse and challenging environments. Hydrogels, with their water-rich "soft and wet" structure, have emerged as promising biomimetic materials in tissue engineering for repairing and replacing damaged tissues and organs. Highly oriented hydrogels can especially emulate the structural orientation found in human tissue, exhibiting unique physiological functions and properties absent in traditional homogeneous isotropic hydrogels. The design and preparation of highly oriented hydrogels involve strategies like including hydrogels with highly oriented nanofillers, polymer-chain networks, void channels, and microfabricated structures. Understanding the specific mechanism of action of how these highly oriented hydrogels affect cell behavior and their biological applications for repairing highly oriented tissues such as the cornea, skin, skeletal muscle, tendon, ligament, cartilage, bone, blood vessels, heart, etc., requires further exploration and generalization. Therefore, this review aims to fill that gap by focusing on the design strategy of highly oriented hydrogels and their application in the field of tissue engineering. Furthermore, we provide a detailed discussion on the application of highly oriented hydrogels in various tissues and organs and the mechanisms through which highly oriented structures influence cell behavior.

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“…Furthermore, introducing patient-derived stem cells in these constructs reduces the risk of graft rejection. The portfolio of 3D bioprinting techniques used for fabricating artificial corneas includes extrusion-based bioprinting, stereolithography (SLA) or digital light processing (DLP)-based bioprinting, inkjet bioprinting, and laser-assisted bioprinting [25]. The ideal dimensions for a bioprinted corneal lenticule are a diameter of ∼13.99 mm, a radius of curvature of ∼7.8 mm, and a total thickness between 500 and 600 µm [26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Biopolymeric corneal lenticules by digital light processing based bioprinting: a dynamic substitute for corneal transplant

Bhutani,

Dey,

Chowdhury

et al. 2024

Biomed. Mater.

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Digital light processing (DLP) technology has gained significant attention for its ability to construct intricate structures for various applications in tissue modeling and regeneration. In this study, we aimed to design corneal lenticules using DLP bioprinting technology, utilizing dual network bioinks to mimic the characteristics of the human cornea. The bioink was prepared using methacrylated hyaluronic acid (HA-MA) and methacrylated gelatin (Gel-MA), where Ruthenium salt (Ru) and sodium persulfate (SPS) were included for mediating photo-crosslinking while tartrazine was used as a photoabsorber. The bioprinted lenticule were optically transparent (85.45 ± 0.14%), exhibited adhesive strength (58.67 ± 17.5 kPa), and compressive modulus (535.42 ± 29.05 kPa) sufficient for supporting corneal tissue integration and regeneration. Puncture resistance tests and drag force analysis further confirmed the excellent mechanical performance of the lenticules enabling their application as potential corneal implants. Additionally, the lenticules demonstrated outstanding support for re-epithelialization and stromal regeneration when assessed with human corneal stromal cells. We generated implant ready corneal lenticules while optimizing bioink and bioprinting parameters, providing valuable solution for individuals suffering from various corneal defects and waiting for corneal transplants.

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Print me a cornea - Are we there yet?

Cited by 4 publications

References 74 publications

Bioprinting of human pluripotent stem cell derived corneal endothelial cells with hydrazone crosslinked hyaluronic acid bioink

Bioprinting of human pluripotent stem cell derived corneal endothelial cells with hydrazone crosslinked hyaluronic acid bioink

Highly oriented hydrogels for tissue regeneration: design strategies, cellular mechanisms, and biomedical applications

Biopolymeric corneal lenticules by digital light processing based bioprinting: a dynamic substitute for corneal transplant

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