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Characterization of cornea-specific bioink: high transparency, improved in vivo safety.

ABSTRACT: Corneal transplantation is a typical surgical procedure for severe corneal diseases. However, the waiting time for a donor cornea has gradually increased due to a decrease in supply caused by an aging population and increased cases of laser-based surgeries. Artificial corneas were developed to meet the increase in demand; however, these approaches have suffered from material deterioration resulted by the limited tissue integration. Here, we introduce a cornea-derived decellularized extracellular matrix (Co-dECM) as a bioink for corneal regeneration. The developed Co-dECM bioink had similar quantitative measurement results for collagen and GAGs compared with that of the native cornea and also had the proper transparency for vision. The differentiation potential of human turbinate-derived mesenchymal stem cells (hTMSCs) to a keratocyte lineage was only observed in the Co-dECM group. Moreover, the developed bioink did not have any cytotoxic effect on encapsulated cells for three-dimensional (3D) culture and has great biocompatibility evident by the xeno-implantation of the Co-dECM gel into mice and rabbits for two and one?month, respectively. An in vivo safety similar to clinical-grade collagen was seen with the Co-dECM, which helped to maintain the keratocyte-specific characteristics in vivo, compared with collagen. Taken together, the Co-dECM bioink has the potential to be used in various types of corneal diseases based on its corneal-specific ability and design flexibility through 3D cell printing technology.

SUBMITTER: Kim H

PROVIDER: S-EPMC6348552 | biostudies-literature | 2019 Jan-Dec

REPOSITORIES: biostudies-literature

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Characterization of cornea-specific bioink: high transparency, improved in vivo safety.

Kim Hyeonji H Park Moon-Nyeo MN Kim Jisoo J Jang Jinah J Kim Hong-Kyun HK Cho Dong-Woo DW

Journal of tissue engineering 20190125

Corneal transplantation is a typical surgical procedure for severe corneal diseases. However, the waiting time for a donor cornea has gradually increased due to a decrease in supply caused by an aging population and increased cases of laser-based surgeries. Artificial corneas were developed to meet the increase in demand; however, these approaches have suffered from material deterioration resulted by the limited tissue integration. Here, we introduce a cornea-derived decellularized extracellular ...[more]

PMID: 30719272

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Project description:Decellularized extracellular matrices (dECMs) represent a promising alternative as a source of materials to develop scaffolds that closely mimic the native environment of cells. As a result, dECMs have attracted significant attention for their applications in regenerative medicine and tissue engineering. One such application is 3D bioprinting, in which dECMs can be used to prepare bioinks with the biomimicry attributes required for regeneration purposes. Formulating bioinks is, however, challenging, due to difficulties in assuring that the printed materials match the mechanical properties of the tissue which is to be regenerated. To tackle this issue, a number of strategies have been devised, including crosslinking methods, the addition of synthetic materials as excipients, and the use of synthetic matrices for casting. We are particularly interested in extrusion-based 3D bioprinting, mainly due to the ease of rapidly conducting tests for adjusting operating conditions such that the required rheological and mechanical properties are met when using it. Here, we propose a novel bioink that consists of an acid-based precipitation of a small intestinal submucosa (SIS) dECM. The formulated bioink also relies on photocrosslinking reactions to attempt to control gelation and ultimately the mechanical properties of the extruded material. Photoinitiation was explored with the aid of varying concentrations of riboflavin (RF). Manual extrusion and rheological flow tests confirmed the printability and shear-thinning behavior of all formulations. Photocrosslinking reactions, however, failed to promote a substantial increase in gelation, which was attributed to considerable entanglement of undigested collagen molecules. As a result, pendant amine groups thought to be involved in the photo-mediated reactions remain largely inaccessible. In silico computational fluid dynamics (CFD) simulations were implemented to determine shear stress values on the bioink along the exit of the printing nozzle. Moreover, we calculated a stability parameter as a means to estimate changes in the bioink stability during the extrusion process. Future studies should be directed toward assessing the role of temperature-induced gelation in the rheological properties of the bioink and the development of strategies to improve the efficiency of photocrosslinking processes.

Dataset Information

Characterization of cornea-specific bioink: high transparency, improved in vivo safety.

Publications

Characterization of cornea-specific bioink: high transparency, improved in vivo safety.

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