| Summary: | 博士 === 國立臺灣大學 === 醫學工程學研究所 === 100 === Corneal endothelial cells (CECs) compose of an intact monolayer in the innermost layer of the cornea and the transparency of the cornea can be sustained only when pump and barrier functions of CECs are maintained. Medically, the corneal endothelium is the most essential part of the cornea, but damages during intraocular surgeries or corneal endothelial diseases such as Fuchs dystrophy can deteriorate the CECs. These events cause corneal edema and opaque which can lead to severe vision impairment, thus corneal transplantation is required to restore cornea clarity and visual acuity.
Conventional penetrating keratoplasty replace the whole corneal layers to treat irreversible opacity. Unfortunately, not only integral structure and optical properties may be altered from a necessary evil of sutures but also higher possibilities of infection and rejection occur. Nevertheless, the majority of corneal transplantations are merely necessary to substitute damaged corneal endothelium. Therefore, supplanting only posterior corneal endothelial layer (endothelial keratoplasty) has numerous benefits including earlier visual recovery, less induced astigmatism and fewer ocular surface complications. Nowadays, the percentage of endothelial keratoplasty increases in the world, but corneal transplantation still faces a global shortage of cornea donors and primary immune rejection.
The development of ex vivo culture system by tissue engineering to establish the cultivated corneal endothelial sheet is the current trend. Fortunately, CECs can be cultivated and expanded in vitro and seeded successfully onto natural tissue materials or synthetic polymeric materials as graft for transplantation. There are three key steps involved: isolation, preservation, and expansion. Traditionally, tissue culture plates (TCPS) were used to cultivate corneal endothelial cells. However, the fibroblastic transformation occurs easily. Once this happens, the CECs would lose their functions. To date, still many novel methods are explored continuously.
Cell behavior is decided by constitutional programs and complex interactions among cells, signals, and matrix. Biomaterial substrates are usually used to grow cells in tissue engineering. Several reports have shown the usefulness of extrinsic signals from soluble growth factors and cell-cell contact for managing the proliferation and differentiation of corneal endothelial cells. Also, cells may proliferative and differentiate well with suitable biomaterials. Here, the effects of hydrophilic and hydrophobic substrate on corneal endothelial cells are unknown. Recent data had shown possible to find the proper biomaterial for the specific cell in many experiments. And the interaction between cell and matrix is important to be surveyed.
Tissue engineering is a new trend in biotechnology using cultured cells and biomaterials to replace damaged tissue and restore impaired functions. After reviewing literatures, we found researching into the behaviors of corneal endothelium on biodegradable polymer membranes had not been inspected well. From our preliminary results, the behavior of corneal endothelial cells would not be the same. Therefore, in the initial part of this study, we try to cultivate corneal endothelial cells on different hydrophilic and hydrophobic polymer membranes. Further efforts to be made are to define the cell-surface interaction among them from investigation of morphology and function.
Based on our findings, the appropriate biomaterials can be applied successfully for cultivation of CECs. Eventually, we hope to make clinical application feasible in the future. The goal to fabricate CEC sheet by means of tissue engineering may not be approached by single biomaterial. Hybridizing two polymers is a method to develop novel biomaterials with combinations of properties from individual. Approved by Food and Drug Administration (FDA), chitosan and polycaprolactone (PCL) are biodegradable biomaterials with various advantages respectively. Furthermore, PCL can be introduced into chitosan easily in a harmonic status by the method of blending without complex chemical modifications.
Towards this aim, in the subsequent part of this study, blends made from various proportions of biodegradable biomaterials (chitosan and PCL) will be examined in the CEC culture systems to elucidate their possible impact on clinical demand and scientific interest. In this study, we will first hypothesize that it is possible to create a new blended biomaterial that can hybridize the characteristics of chitosan and PCL concurrently to serve as a scaffold and carrier for CEC culture and transplantation. In the future, we hope to provide a model and design transplantation graft for possible clinical applications in tissue engineering and regenerative medicine of the corneal endothelium.
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