Manufacturing, as we know it, will never be the same. 3D printing that has already been known for decades has revolutionized various industries with its ever-advancing technology. This has been possible by augmenting the capabilities of existing methods of manufacturing, materials used and range of applications. Through its better creativity, customizability and sustainability, it has successfully penetrated aerospace to automotive to health care to biotechnology.

The focus of the scientific community has shifted towards transformative applications of bio-nanotechnology and finding revolutionary approaches for the reconstruction and regeneration of human tissues and organs. This is where 3D printing comes in.

The technology uses biomaterials, cells, proteins, and other biological compounds as building blocks to make up 3D structures (artificial organs) in layer-by-layer fashion.

Scientists at Newcastle University, UK, have developed 3D printed cornea using a simple, low-cost 3D bio-printer that extrudes bio-ink in concentric circles to form the shape of the human cornea. Such attempts show novel approaches that can accelerate the realization of anatomically correct tissue constructs for transplantation. In the future decades, and in combination with synthetic biology and nanotechnology, it has the potential to radically transform the biomedical field.

According to recent reports, “about 53% of the world’s population had no access to corneal transplantation. There is a considerable shortage of corneal graft tissue, with only 1 cornea available for 70 needed”.

According to American Academy of Ophthalmology, “if the cornea is scarred, swollen, or damaged, light is not focused properly in the eye leading to blurry vision or cause a glare. If cornea cannot be healed or repaired, the ophthalmologist may recommend a corneal transplant. This is when the diseased cornea is replaced with a clear, healthy cornea from a human donor. There are different types of corneal transplants. In some cases, only the front and middle layers of the cornea are replaced. In others, only the inner layer is removed. Sometimes, the entire cornea needs to be replaced.”

Diseases and injuries that can damage the cornea are Keratoconus, Fuchs’ dystrophy, corneal ectasia, fungal keratitis, Acanthamoeba keratitis, chalazion, corneal abrasion, previous corneal surgery or another eye surgery that damaged the cornea.

Most people receive a replacement cornea from a human donor. Although the surgery has a high success rate, the supply of donor tissue is limited. In the developing world, access to donor tissue is even more difficult. Furthermore, while human donor transplants are the standard treatment for corneal blindness, the complications and limitations inherent in them have prompted development of synthetic corneal substitutes. Existing synthetic corneas can be categorized into:

• Fully synthetic prostheses (e.g., keratoprostheses); and
• Hydrogels that permit regeneration of the host tissue.

Till now, only three patents have been filed that explicitly disclose the method for 3D printing a human eye cornea. They are:

• In 2015, University of California filed patent disclosing the fabrication method of an artificial cornea by separately culturing live stromal cells, live corneal endothelial cells (CECs) and live corneal epithelial cells (CEpCs). Separate stromal, CEC and CEpC layers are printed using 3D bio-printing method to encapsulate the cells into separate hydrogel nanomeshes. The CEC layer is attached to a one side of the stromal layer and the CEpC layer to another thereby defining the artificial cornea. The CEC layer is attached to stromal layer by applying a thin film of hydrogel between each of the layers and curing via UV exposure. The patent discloses the use of acryloyl-PEG-collagen and methacrylated hyaluronan to prepare the bio-ink. Further, the live CEpCs and CECs are cultured and differentiated from limbal stem cells (obtained from autologous tissue) and CEC progenitors (obtained from autologous tissue).
• In 2015, Shenzhen Huaming Biology Technology filed an invention disclosing the preparation method of an artificial cornea based on 3D printing technology. The manufacturing method includes setting up a human vision model; making up a personal eyeball model by 3D scanning; importing data into a 3D printer; preparing printing materials; scanning the printing materials point-by-point through ultraviolet laser beams with wave length in 355 nm and beam quality M2 in 1.0-1.3, curing the liquid-state printing materials from point to line and line to surface, regulating a lifting platform to move by a computer, curing the liquid-state printing materials layer by layer, and finally stacking layer by layer to obtain a 3D-printed cured product; freezing and forming and successively processing. The material is a liquid prepolymer or a liquid printing HEMAPVA hydrogel with azide benzoic acid, methyl acrylate, polyethylene glycol and a volume ratio of the compound in any subunot 6:1 or 10:1 formulated with the mixture. The photo-initiator is α-hydroxy alkyl ketones.
• Pohang University of Science and Technology filed a patent disclosing the method for preparing biocompatible cornea and decellularization composition for a    biocompatible tissue. The method includes providing a cornea from a tissue source through corneal incision; decellularizing the provided cornea in purified water containing charcoal for a predetermined time; and post-treating the decellularized corneal extracellular matrix through, stirring in a hypotonic solution, so that the charcoal is used as a decellularizing agent for the cornea, thereby allowing the regeneration of a corneal tissue like in the original corneal extracellular matrix, and the preparation of a cornea without an immune rejection response and a fast regeneration effect of a patient through transplantation of the cornea can be expected. After the step of inducing gelation, injecting the gelated bio-ink into a 3D printer, and preparing a cornea matching the size of a scanned affected part of a transplant recipient using the 3D printer; transplanting the prepared cornea into the transplant recipient.

Several organizations like Bacterin International have filed patents that disclose the 3D printed biomaterials-based implants and have a general focus on 3D printed cornea.

Apart from making 3D printed cornea, various organizations and academia like Qingdao Sandi Biotechnology, John Hopkins University etc. have found other applications of 3D printing technology in cornea implantation. Some of them are:

• A three-dimensional (3D) cornea stroma support material and a method for constructing a 3D cornea stroma support.
• A cornea scaffold material and its preparation method for treating the stromal layer of the cornea.
• Cornea three-dimensional scaffold is prepared using 3D bio-printer utilizing multipolymer that serves as the raw material.
• The apparatus for isolating corneal endothelial cells (CECs) is manufactured using 3D printing method.

Final Thoughts

It is well known that the corneas donated for corneal transplants are extremely insufficient, and complications, such as infections and immune responses, may be developed after the cornea transplant. Also, the scientific community has also realized the need to develop corneal bioengineering solutions, such as 3D printed cornea. However, there is need to study materials like alginate, collagen, etc. that can not only be used to prepare bio-inks for printing corneas, but also can support cell growth within the construct and recruit host cells for better integration of the constructs.

Nothing can surpass the precision and accuracy of 3D printing methods, but more efforts will be needed to maintain a highly homogenous cellular distribution within each layer while 3D printing the cornea and precise control of the spatial localization of different layers like epithelium layer, Bowman’s layer, stromal layer, Descemet’s layer and endothelium layer.

Since the technology is slightly unusual and very few patents are filed in this technological field, academia and organizations can easily penetrate and file their patents related to fabrication method, material compositions, 3D printing apparatus, scanning techniques, etc. to produce the human eye cornea.

• The Engineering and Editorial Team

Having Queries? Contact Us Now!