Abstract

Retinal degeneration is a leading cause of incurable vision loss and blindness. The increasing incidence of retinal degeneration has triggered research into the development of in vitro retinal models for drug development and retinal alternatives for transplantation. However, the complex retinal structure and the retinal microenvironment pose serious challenges. Although 3D cell printing technology has been widely used in tissue engineering, including in vitro model development and regeneration medicine, currently available bioinks are insufficient to recapitulate the complex extracellular matrix environment of the retina. Therefore, in this study, we developed a retinal decellularized extracellular matrix (RdECM) from the porcine retina and evaluated its characteristics. The RdECM conserved the ECM components from the native retina without cellular components. Then, we mixed the RdECM with collagen to form a bioink and confirmed its suitability for 3D cell printing. We further studied the effect of the RdECM bioink on the differentiation of Muller cells. The retinal protective effect of the RdECM bioink was confirmed through a retinal degeneration animal model. Thus, we believe that the RdECM bioink is a promising candidate for retinal tissue engineering.

Highlights

  • The retina is the light-sensitive layer of the ocular system and is composed of various cells that allow translation of the focused image to electrical signals, which are transferred to the brain for visual image processing [1,2]

  • The results of this study suggest that the retinal decellularized extracellular matrix (RdECM) bioink could be used for the development of retinal alternatives and for establishing in vitro models

  • The RdECM bioink was developed from the porcine retina through multiple processes including chemical and enzymatic treatment, lyophilization, and pepsin digestion (Figure S1)

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Summary

Introduction

The retina is the light-sensitive layer of the ocular system and is composed of various cells that allow translation of the focused image to electrical signals, which are transferred to the brain for visual image processing [1,2]. Due to its crucial role in vision, damage to this layer breaks down the visual system and causes a wide range of impairments related to vision loss, such as age-related macular degeneration, diabetic retinopathy, and retinitis pigmentosa [3,4,5]. These impairments are the leading causes of global blindness, but no effective treatment exists. Transplantation is one of the promising treatments to replenish the damaged retina, for which several strategies have been adopted, including cell injection and the implantation of cell sheets [6,7,8,9].

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