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Received Nov 27, 2017; Revised Feb 22, 2018; Accepted Mar 19, 2018
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1. Introduction
The human cornea is the outermost, transparent tissue of the eye. It is the principal refractive element of the visual system, and its function depends mainly on its optical clarity. Human corneal endothelial cells (HCEnCs) are responsible for maintaining this transparency through a pump-and-leak mechanism [1]. To do so, this leaky barrier of hexagonally shaped cells allows passive diffusion of nutrients flowing from the anterior chamber to the corneal stroma and epithelium but simultaneously averts corneal edema by pumping excessive fluid back to the anterior chamber.
Due to a mitotic arrest in vivo after birth, the number of endothelial cells decreases throughout life [2]. However, this decay can dramatically be accelerated by trauma or several diseases. If the overall number of HCEnCs drops below a certain threshold of less than 500 cells/mm2, irreversible edema eventually arises, leading to an opaque cornea.
The only available treatment currently is corneal endothelial transplantation, termed endothelial keratoplasty (EK). In 2016, nearly 40% of donated corneas distributed by US eye banks were transplanted to treat endothelial dysfunction. Although EK has a high success rate in terms of visual rehabilitation and postoperative visual outcome, transplantations are often restricted by a shortage of corneal donor tissue [3].
In order to overcome this scarcity, alternative therapeutic approaches such as ex vivo expansion of HCEnCs are under investigation to enable HCEnCs transplantation as cell sheets or cell suspension [4–7]. Once HCEnCs from one donor eye can successfully be expanded, we would finally be able to overcome the current 1 : 1 ratio where one donor cornea is used to treat a single patient. Consequently, waiting lists would shorten significantly. In case of the cell sheet transplantation strategy, a scaffold is required which will act as a mechanical support (i.e., a surrogate basement membrane) that can sustain cell proliferation and phenotype. Multiple scaffolds have been reported as candidate membranes, and among these options, three different categories can be identified: (i) biological, (ii) synthetic, and (iii) biosynthetic substrates [5].
In 2010, Lin...