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.
Highlights
The cornea is a thin tissue layer that is responsible for the protection of intraocular structures and refraction of light [1]
Liang et al have demonstrated that a carrier membrane made of hydroxyethyl chitosan, gelatin, and chondroitin sulfate is suitable for corneal endothelial cell (CEC) to attach and grow [5]
The present study reports the development of overrun-processed porous Hyaluronic acid (HA) hydrogels as cell sheet delivery carriers for corneal endothelial transplantation and reconstruction
Summary
The cornea is a thin tissue layer that is responsible for the protection of intraocular structures and refraction of light [1]. Corneal endothelial tissue engineering is a promising alternative to corneal transplantation [3]. As early as 1990, Insler et al have reported a method to transplant corneal endothelial cells (CECs) expanded ex vivo on the carriers made of collagen-coated dextran [4]. Naturally occurring biopolymer such as chitosan has been widely used to engineer CEC culture substrates. Ozcelik et al have shown that an ultrathin chitosanpoly(ethylene glycol) hydrogel film displays excellent characteristics (i.e., desirable mechanical, optical and degradation properties) for corneal endothelial tissue engineering applications [6]. It should be noted that the problems involving the implantation of CEC-populated carrier substrates may include poor graft-host integration, optical interference, risk of foreign body reaction, and disturbance of physiological function
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