The Innovative Biomaterials and Technologies for Developing Corneal Endothelium Tissue Engineering Scaffolds: A Review and Prospect

Abstract

Corneal transplantation is the only treatment for corneal endothelial blindness. However, there is an urgent need to find substitutes for corneal endothelium grafts due to the global shortage of donor corneas. An emerging research field focuses on the construction of scaffold-based corneal endothelium tissue engineering (CETE). Long-term success in CETE transplantation may be achieved by selecting the appropriate biomaterials as scaffolds of corneal endothelial cells and adding bioactive materials to promote cell activity. This article reviews the research progress of CETE biomaterials in the past 20 years, describes the key characteristics required for corneal endothelial scaffolds, and summarizes the types of materials that have been reported. Based on these, we list feasible improvement strategies for biomaterials innovation. In addition, we describe the improved techniques for the scaffolds' surface topography and drug delivery system. Some promising technologies for constructing CETE are proposed. However, some questions have not been answered yet, and clinical trials and industrialization should be carried out with caution.

Keywords: biomaterials; corneal endothelium tissue engineering; drug delivery; innovative technologies; surface topography.

Figure 1

Scheme of corneal endothelial tissue engineering (CETE) constructed based on scaffolds and seed cells. Human corneal endothelial cells (hCECs), as the seed cells, can be derived from donor corneas isolation, human pluripotent stem cells (hPSCs) differentiation, or other types of cells transdifferentiation. Increased hCECs can be obtained by expansion in vitro. The source of scaffolds includes natural, synthetic, or semi-synthetic materials. The scaffold is fabricated through techniques including 3D bioprinting and electrospinning. Finally, hCECs are loaded onto the scaffold to create a CETE graft. These grafts can then be inserted into the cornea’s posterior surface of an animal for research purposes with the eventual goal of transplanting into humans.

Figure 2

Schematics of key properties for CETE scaffold. Imitating the native Descemet’s membrane, the scaffold acts as an extracellular matrix (ECM), providing suitable microenvironment and signal support for the behavior of CECs. Transparency, nutrient permeability, proper mechanical strength, biocompatibility, and ability to maintain the differentiated state of CECs are some of the specific characteristics.

Figure 3

Schematics of the adhering hCECs and the ECM structure of Descemet’s membrane. (A) Five layers of the corneal tissue. (B) The ECM of Descemet’s membrane provides suitable surface topography for hCECs. (C) The ECM structure of Descemet’s membrane. Images are created by Biorender.com.