Fabricating Bioengineered Corneal Endothelium on Chitosan-Polycaprolactone Blends---Experiment, Mechanism, and Application

Based on our recent publications (J Biomed Mater Res A 2012;100:252-260. and Colloids and Surface B: Biointerfaces 2012;90:236-43. and Molecular Vision 2012; 18: 255-64. ), the appropriate biomaterials can be applied successfully for cultivation of corneal endothelial cells (CECs). CECs compose of an intact monolayer in the innermost layer of the cornea. 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 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. 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. To date, still many novel methods are explored continuously. 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. 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, 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, 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 be a scaffold and carrier for CEC culture and transplantation. Second, we will investigate the mechanism of signal transduction between cultivated cells and appropriate blends. Finally, an in vitro model of corneal edema will be established and used to evaluate the function of bioengineered corneal endothelium. 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.