Decellularization and recellularization of cornea: Progress towards a donor alternative

Abstract

The global shortage of donor corneas for transplantation has led to corneal bioengineering being investigated as a method to generate transplantable tissues. Decellularized corneas are among the most promising materials for engineering corneal tissue since they replicate the complex structure and composition of real corneas. Decellularization is a process that aims to remove cells from organs or tissues resulting in a cell-free scaffold consisting of the tissues extracellular matrix. Here different decellularization techniques are described, including physical, chemical and biological methods. Analytical techniques to confirm decellularization efficiency are also discussed. Different cell sources for the recellularization of the three layers of the cornea, recellularization methods used in the literature and techniques used to assess the outcome of the implantation of such scaffolds are examined. Studies involving the application of decellularized corneas in animal models and human clinical studies are discussed. Finally, challenges for this technology are explored involving scalability, automatization and regulatory affairs.

Prospects and Challenges of Translational Corneal Bioprinting

“…The key difference in the protocols is the preservation of the crucial membranes in the tissue, i.e., Bowmans and Descemets with respect to decellularization efficiency [45][46][47]. Drawbacks that remain are the loss of ECM components, alterations of the stromal structure, and biomechanical stability as well as inability to allow a complete recellularization by the host's CSKs post-implantation [45][46][47][48].…”

Corneal xenotransplantation: Where are we standing?

“…The decellularized methods for DPCs (used alone or in combination) are classified into three categories: chemical, physical, and biological ( Fernandez-Perez and Ahearne, 2020 ). Chemical decellularization applies detergents including sodium dodecyl sulfate (SDS), sodium deoxycholate, Triton X-100, peracetic acid, formic acid, ammonium hydroxide, sodium chloride, and ethylenediaminetetraacetic acid (EDTA).…”

The progress in corneal translational medicine

“…Nevertheless, they do promote dendritic branching, cell elongation, and CSK expression of keratocan and ALDH in vitro. 228 Other substances, that have been investigated as alternative stromal biomaterials include PLGA, gelatin, and chondroitin sulfate. 229,230 Cell-free corneal implants comprising recombinant human collagen and phosphorylcholine were recently grafted by anterior lamellar keratoplasty into the corneas of unilaterally blind patients diagnosed at high-risk for transplant rejection.…”

“…[225][226][227] The drawbacks that still need to be addressed are the loss of ECM components, alterations of the stromal structure, biomechanical stability and inability to allow complete recellularization by the host's CSKs post-implantation. [225][226][227][228] Endothelium: Human CECs are postmitotic in vivo, and thus do not proliferate. However, in vitro, hCECs have been expanded and reinjected into the eyes of patients with endothelial disease.…”