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International Journal of Bioprinting 3D bioprinting for corneal regeneration

for 9.5%, ulcerative keratitis for 2.6%, and injuries for medicine for corneal replacement, addressing the challenge
2.4%. Subsequently, a separate study conducted between of donor shortage. 7
3
August 2012 and August 2013 highlighted a substantial
global demand for corneal transplants, estimating that 2. The structure of the cornea
12.7 million individuals across 131 countries awaited The cornea, a thin and transparent membrane, serves two
this procedure. In stark contrast, the annual incidence primary functions: protecting the interior of the eye and
4
of corneal transplants in the United States is limited facilitating light refraction. Optically, it is responsible for
to 40,000. 5 two-thirds of light refraction. The structural composition
The treatment landscape is significantly challenged of the cornea involves various cell types, including
by the pronounced disjunction between the number epithelial cells, keratocytes, stromal cells, and corneal
of patients awaiting transplantation and the limited endothelial cells. In addition, extracellular components
availability of cornea donors. This stark demand has such as collagen or glycosaminoglycans (GAG) contribute
prompted intensive research and development efforts to its composition.
in the realm of artificial cornea and cornea replacement The cornea is anatomically divided into five principal
products, which must meet stringent criteria. Even layers: epithelium, Bowman’s membrane, stroma,
6
when a suitable cornea donor is identified, the healing Descemet’s membrane, and endothelium (Figure 1). In
process may face impediments due to immune response- terms of structure, the epithelial layer has a thickness of
driven rejection. The evolving landscape of science and 5–7 cells, comprising three cell types: surface epithelial
5
medicine has ushered in myriad possibilities in the field cells, stem cells, and basal cells. These cells collectively
of corneal research. The contemporary medical arena form a uniform layer with a thickness of 50 µm. Notably,
increasingly embraces personalized therapies, a trend corneal epithelial cells differentiate from limbal epithelial
underscored by the advent of translational biomedicine. stem cells (LESCs) and do not undergo keratinization.
8
A noteworthy surge in possibilities, such as the adoption Following the epithelial layer, Bowman’s membrane,
of three-dimensional (3D) bioprinting, is reshaping the characterized by an acellular structure, is constructed
field. Traditional surgical approaches for reconstructing from a disordered multitude of collagen fibers. The stroma,
various tissues and organs confront formidable challenges which represents the thickest layer and constitutes roughly
owing to the distinctive functions of these tissues. To 90% of the total corneal thickness, plays an essential role
overcome these limitations, there has been a discernible in providing mechanical strength and critical optical
escalation in research dedicated to the application of 3D properties. Structurally, it comprises approximately
printing techniques. 200–250 parallel collagen fibers. Similar to Bowman’s

In corneal tissue engineering, in addition to 3D layer, Descemet’s membrane is also acellular, composed
printing, nanotechnology offers a new avenue thanks of collagen, laminin, and fibronectin. The last layer of the
to recent physical and chemical breakthroughs. These cornea is the endothelial layer, semi-permeable to water
advancements enable the creation of specialized surfaces and nutrients. Due to this property, the endothelial layer
that facilitate cell adhesion and proliferation, establishing ensures fluid flow for the stroma. However, it is noteworthy
unique microenvironments to enhance nutrient supply. that the number of cells forming the endothelial layer
By incorporating various nanomaterials into hydrogels, it decreases with aging, and the proliferation capacity of
becomes possible to influence the physical and mechanical these cells is significantly lower in the adult cornea. 9,10
properties of the gel, including gelation. Nanoliposomes, In addition to the well-established five layers, a sixth
when combined with stem cells in the gel, can mediate layer was recently discovered in 2013 by Dua and his
active substances, facilitating cell differentiation, colleagues. 11,12 Termed pre-Descemet’s or Dua’s layer, this
reducing inflammation, and enhancing wound healing. membrane is located anterior to Descemet’s layer. Dua’s
The promising properties and versatile applications of layer is a thin membrane primarily composed of type IV
nanomaterials hold potential for the future of corneal collagen, with a thickness ranging from 6 to 15 µm. The
tissue engineering and regenerative medicine. However, it collagen fibers within this layer are organized into 5–8
is important to note that the application of this technology layers. 8,9,11
in this field is still in the early stages of research. 5
3. Cells of the cornea
In 3D bioprinting for regenerative medicine, we are
already witnessing promising results that allow for the 3.1. Corneal epithelium
printing of tissues with complex structures. Consequently, The corneal epithelium acts as a physical barrier,
3D bioprinting presents a new opportunity in personalized consisting of three different cell types: surface squamous

Volume 10 Issue 2 (2024) 108 doi: 10.36922/ijb.1669