Engineering of corneal stroma and posterior cornea tissues towards applications in corneal transplantation

Blindness and low vision severely diminish the quality of life, and research has shown that going blind is the most feared disability. The cornea is the front-most tissue of the eye, serving to protect the inner parts of the eye and working with the lens to focus light onto the retina. Damage or disease can manifest into an opaque or misshaped cornea. An opaque cornea blocks light from reaching the retina while a misshaped cornea is incapable of focusing light. Both cases can lead to vision loss and corneal-related blindness. Depending on the cause, whole or partial-thickness cornea transplantation, such as deep anterior lamellar keratoplasty (DALK) and Descemet stripping endothelial keratoplasty (DSEAK), can improve the patient’s vision. However, donor corneal tissue comes from cadaveric sources and there is an unmet demand for transplantable corneas. Engineered partial thickness or whole corneal scaffolds can help close this gap. The long-term vision of this thesis is to engineer partial-thickness corneal constructs and used them in transplantation procedures. To accomplish this, constructs must be capable of withstanding handling during surgery, be transparent after transplantation, and integrate into the host cornea without causing a pathological host response. In this thesis, I combine biomaterials engineering, protein assembly, and patient-derived corneal stromal stem cells. In chapter 2, I fabricated a multilayered cornea stroma construct with the potential of being used in DALK procedures. In chapter 3, I integrated an engineered endothelium with multilayered stroma constructs to assemble an engineered posterior cornea (EPC). The EPC integrated onto an ex-vivo rabbit cornea after implantation using a DSEAK-like procedure. Lastly, in chapter 4, I initiate the work for a corneal stroma bioreactor that can be used with a multilayered stroma construct or EPC to understand the effects of pressure on extracellular matrix assembly and fabricate better corneal tissues. This thesis provides valuable data and a platform to build transplantable tissues and models. Future directions include evaluating the multilayered cornea stroma construct in an animal DALK procedure and the EPC on a DSEAK procedure, as well as, generating a whole cornea construct.