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International Journal of Bioprinting 3D bioprinting for corneal regeneration

addition, the optical properties of these products must the need for two surgical procedures in many cases, thereby
closely align with those of the native cornea while also elevating the risk of infections. 7
demonstrating resilience to withstand transplantation and
mitigate the risk of eliciting autoimmune reactions from 5.2. Amniotic membrane
the recipient’s body. In addition to keratoprostheses, the amniotic membrane
(AM) stands out as one of the most commonly used
5.1. Keratoprostheses corneal substitutes. Derived from the placenta, the
Blindness resulting from disease or corneal damage amniotic membrane is typically 0.02–0.5 mm thick and
constitutes a significant global health concern affecting devoid of blood vessels and nerves. Structurally, the AM
millions of individuals. Corneal transplantation, or consists of three layers: the epithelial layer, the vascular
keratoplasty, stands as the primary method for addressing stroma, and the basement membrane. Both the basement
corneal blindness. However, the scarcity of suitable donors membrane and the stroma are rich in collagen, fibronectin,
poses a considerable challenge in caring for affected and laminin. The membrane serves multifaceted functions,
patients. Consequently, biomimetic substitutes that promoting the migration of epithelial cells, orchestrating
emulate the cornea have gained increasing prominence. the organization of collagen fibers, and concurrently
inhibiting neovascularization and fibrosis. 30
Artificial corneas, known as keratoprostheses, are
laboratory-manufactured products comprising both Several studies have explored the applicability of the
synthetic and biological materials. These substitutes offer amniotic membrane, including research conducted by
31
many advantages, including enhanced biocompatibility Rohaina et al. In their study, the amnion was combined
that mitigates the risk of rejection. Adhering to strict with stem cells for epithelial replacement, revealing
manufacturing regulations ensures the sterility of enhanced post-operative transparency of the implanted
keratoprostheses, minimizing the risk of infections during AM attributed to reduced neovascularization. These
implantation, which could potentially lead to further findings suggest that the AM holds promise as a corneal
corneal damage. Notably, keratoprostheses exhibit reduced substitute in corneal reconstruction surgeries.
light scattering owing to their unique properties. 28 Efforts have also been directed toward enhancing the
The evolution of these products over the years reflects stability and durability of the membrane by incorporating
substantial advancements. Early keratoprostheses had additional scaffolds, often involving various nanomaterials
a more artificial effect than the current, more advanced and nanofibers. However, the use of such supporting
artificial corneas. The center of the early versions of these elements introduces uncertainties, including uncontrolled
products featured a rigid, poly(methyl methacrylate) degradation, tissue interaction, and potential cytotoxicity.
(PMMA) optical element attached by synthetic or Despite these challenges, the use of AM is not without
alternative materials. However, challenges in patient disadvantages, encompassing limitations such as the
implantation arose due to potential immune responses restricted number of available donors, difficulties in isolation
triggered by certain materials. Research suggests that from the placenta, and the inherent risks of infections that
32,33
porous materials such as Teflon, poly(2-hydroxyethyl could be transmitted through transplantation.
methacrylate), or Dacron (polyethylene terephthalate 5.3. Corneal bioscaffolds
[PET]) facilitate the integration of implants into the host The development of artificial tissue production has
body, potentially addressing these challenges. 29 presented a new opportunity to address the shortage of
However, these prostheses come with inherent cornea donors. One approach involves combining real
limitations and disadvantages, partly stemming from the tissue with an artificial scaffold crafted from biomaterial.
structure and material composition of the implants. The In comparison to keratoprostheses, these products may
typical hardness and relative rigidity of these materials can offer greater ease in terms of biocompatibility. Careful
induce discomfort upon implantation in the patient’s eyes, consideration of the chosen scaffold material and its
potentially causing damage to the surrounding healthy preparation is crucial during the planning of these
tissue. Another disadvantage is the restricted vision often substitutes to ensure resulting tissue closely mimics
32
experienced post-keratoplasty, a consequence of the native tissue.
material used for implant fixation. The choice of fixation Another alternative involves using decellularized
material may compromise corneal transparency. Given corneal stroma of animal origin, providing a potential
the implantation of artificial materials, the transplantation remedy for the donor shortage. The effectiveness of using
process becomes more complicated than allografts, with these scaffolds for stroma reconstruction is heightened

Volume 10 Issue 2 (2024) 112 doi: 10.36922/ijb.1669