Use of biomaterials in corneal endothelial repair

Abstract

Human corneal endothelium (HCE) is a single layer of hexagonal cells that lines the posterior surface of the cornea. It forms the barrier that separates the aqueous humor from the rest of the corneal layers (stroma and epithelium layer). This layer plays a fundamental role in maintaining the hydration and transparency of the cornea, which in turn ensures a clear vision. In vivo, human corneal endothelial cells (HCECs) are generally believed to be nonproliferating. In many cases, due to their nonproliferative nature, any damage to these cells can lead to further issues with Descemet's membrane (DM), stroma and epithelium which may ultimately lead to hazy vision and blindness. Endothelial keratoplasties such as Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet's membrane endothelial keratoplasty (DEK) are the standard surgeries routinely used to restore vision following endothelial failure. Basically, these two similar surgical techniques involve the replacement of the diseased endothelial layer in the center of the cornea by a healthy layer taken from a donor cornea. Globally, eye banks are facing an increased demand to provide corneas that have suitable features for transplantation. Consequently, it can be stated that there is a significant shortage of corneal grafting tissue; for every 70 corneas required, only 1 is available. Nowadays, eye banks face long waiting lists due to shortage of donors, seriously aggravated when compared with previous years, due to the global COVID-19 pandemic. Thus, there is an urgent need to find alternative and more sustainable sources for treating endothelial diseases, such as utilizing bioengineering to use of biomaterials as a remedy. The current review focuses on the use of biomaterials to repair the corneal endothelium. A range of biomaterials have been considered based on their promising results and outstanding features, including previous studies and their key findings in the context of each biomaterial.

Keywords: Descemet’s membrane (DM); biomaterials; cornea; corneal transplantation; human corneal endothelial cells (HCECs); scaffold; tissue engineering.

Figure 1.

Diagram of the human cornea location and structure. Source: Author’s illustration.

Figure 2.

Overview of the concept of corneal bioengineering and regeneration therapy of human corneal endothelial cells (HCECs), which ultimately is aimed at alleviating the global shortage in donor cornea tissues. General steps have been summarized. (a) The corneal endothelial cell sources: primary cells isolated from a donor cornea, immortalized cell lines, or stem cells. (b) In vitro cell expansion is the next step with the necessity to maintain healthy phenotype and morphology. The delivery system of the expanded corneal endothelial cells to the posterior corneal surface is achieved using (c) cell injection therapy or (d) using various types of biomaterials to fabricate corneal endothelial cell scaffold. (e) The implantation stage of the cultured scaffold into the anterior chamber through a similar DMEK/DSAEK transplantation. (f) Parallel studies on the scaffold are carried out to investigate whether the scaffold is working effectively. (g) Corneal bioengineering and regeneration therapy can alleviate the shortage of native corneas and help improve the quality of life for many patients who are waiting their turn for cornea tissue transplantation. Source: Author’s illustration.

Figure 3.

(a) The structure of human AM, and the composition of extracellular matrix for each layer (Source: Leal-Marin and colleagues). (b) The illustration displays placenta and fetal membranes. (c) The fetal bag (membranes) can be viewed on the placenta with a surgical incision noticeable. (d) An isolate and dispersed human AM is seen. The circle shows the placental human AM (proximal) area and the stars show the peripheral human AM (distal) areas (Source: Grémare and colleagues).

Figure 4.

Diagram showing the general approach for using decellularized tissues for corneal endothelial cells’ bioengineering. Source: Author’s illustration.

Figure 5.

Analysis by scanning electron microscopy of collagen gel shows the difference between (a) uncompressed gel and (b) compressed gel. Collagen fibers on the surface of the uncompressed gel are displayed in a disorganized and very loosely arranged manner, whereas the collagen fibers in the compressed gel are more densely packed and homogeneous. Source: Mi and colleagues.

Figure 6.

Photos show the high transparency of ‘pure chitosan’ and largely high transparent ‘blended chitosan with polycaprolactone’ (PCL25, PLC50, PCL75, but not PCL100), comparing with tissue culture polystyrene (TCPS) plates. Source: Wang and colleagues.

Figure 7.

Figure (a) shows agarose membrane is transparent and robust enough to be handled with a pair of forceps and (b) Despite the thickness was being ~8 mm, the conjugated agarose gel with fish-derived gelatin (AG) showed excellent transparency (the red star indicates the agarose gel). Source: Seow and colleagues.

Figure 8.

(a) Poly-ε-lysine hydrogel forms a thin transparent film. (b) Microporous structure of the poly-ε-lysine hydrogel under atomic force microscope (AFM). (c) Poly-ε-lysine hydrogels can be manipulated easily using forceps. Source: Kennedy and colleagues.