title: Investigation of Overrun-Processed Porous Hyaluronic Acid Carriers in Corneal Endothelial Tissue Engineering.
abstract: Hyaluronic acid (HA) is a linear polysaccharide naturally found in the eye and therefore is one of the most promising biomaterials for corneal endothelial regenerative medicine. This study reports, for the first time, the development of overrun-processed porous HA hydrogels for corneal endothelial cell (CEC) sheet transplantation and tissue engineering applications. The hydrogel carriers were characterized to examine their structures and functions. Evaluations of carbodiimide cross-linked air-dried and freeze-dried HA samples were conducted simultaneously for comparison. The results indicated that during the fabrication of freeze-dried HA discs, a technique of introducing gas bubbles in the aqueous biopolymer solutions can be used to enlarge pore structure and prevent dense surface skin formation. Among all the groups studied, the overrun-processed porous HA carriers show the greatest biological stability, the highest freezable water content and glucose permeability, and the minimized adverse effects on ionic pump function of rabbit CECs. After transfer and attachment of bioengineered CEC sheets to the overrun-processed HA hydrogel carriers, the therapeutic efficacy of cell/biopolymer constructs was tested using a rabbit model with corneal endothelial dysfunction. Clinical observations including slit-lamp biomicroscopy, specular microscopy, and corneal thickness measurements showed that the construct implants can regenerate corneal endothelium and restore corneal transparency at 4 weeks postoperatively. Our findings suggest that cell sheet transplantation using overrun-processed porous HA hydrogels offers a new way to reconstruct the posterior corneal surface and improve endothelial tissue function.
authors: Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan, 33302, Republic of China; Biomedical Engineering Research Center, Chang Gung University, Taoyuan, Taiwan, 33302, Republic of China; Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan, 33302, Republic of China.
authors: Jui-Yang
authors: JY
authors: Lai
authors: Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan, 33302, Republic of China.
authors: Hsiao-Yun
authors: HY
authors: Cheng
authors: Limbal Stem Cell Laboratory, Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, 33305, Republic of China; Department of Chinese Medicine, Chang Gung University, Taoyuan, Taiwan, 33302, Republic of China.
authors: David Hui-Kang
authors: DH
authors: Ma
mesh_terms: D000818:Animals; D002234:Carbodiimides / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004728:Endothelium, Corneal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D020100:Hydrogels / Q000737:chemistry / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D016062:Porosity; D061251:Primary Cell Culture; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D002234:Carbodiimides; D003432:Cross-Linking Reagents; D020100:Hydrogels; D006820:Hyaluronic Acid; D000254:Sodium-Potassium-Exchanging ATPase