Artificial human corneas - Scaffolds for transplantation and host regeneration
ABSTRACT To review the development of artificial corneas (prostheses and tissue equivalents) for transplantation, and to provide recent updates on our tissue-engineered replacement corneas.
Modified natural polymers and synthetic polymers were screened for their potential to replace damaged portions of the human cornea or the entire corneal thickness. These polymers, combined with cells derived from each of the three main corneal layers or stem cells, were used to develop artificial corneas. Functional testing was performed in vitro. Trials of biocompatibility and immune and inflammatory reactions were performed by implanting the most promising polymers into rabbit corneas.
Collagen-based biopolymers, combined with synthetic crosslinkers or copolymers, formed effective scaffolds for developing prototype artificial corneas that could be used as tissue replacements in the future. We have previously developed an artificial cornea that mimicked key morphologic and functional properties of the human cornea. The addition of synthetic polymers increased its toughness as it retained transparency and low light scattering, making the matrix scaffold more suitable for transplantation. These new composites were implanted into rabbits without causing any acute inflammation or immune response. We have also fabricated full-thickness composites that can be fully sutured. However, the long-term effects of these artificial corneas need to be evaluated.
Novel tissue-engineered corneas that comprise composites of natural and synthetic biopolymers together with corneal cell lines or stem cells will, in the future, replace portions of the cornea that are damaged. Our results provide a basis for the development of both implantable temporary and permanent corneal replacements.
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ABSTRACT: Although one of the most transplanted tissues, a shortage of cadaveric corneas for transplantation still exists in the western society and elsewhere. The goal of this study was to develop a biological scaffold to support transfer of cultured human corneal endothelial cells (HCECs) into the anterior chamber of the eye, potentially a replacement for cadaveric donor tissue. A series of transparent scaffolds were fabricated from gelatin and modified with heparin. Mechanical parameters of the scaffolds, such as stiffness, affected cell proliferation, phenotype and cell surface marker expression were determined. The heparin-modified scaffolds had a greater capacity to absorb basic fibroblast growth factor (bFGF) and showed better release kinetics for up to 20 days. The release of bFGF from the scaffolds improved HCECs survival and reduced cellular loss. The scaffolds were flexible and could be folded and implanted in rabbits' eyes, through a small incision in the cornea. The scaffolds adhered to the inner surface of the corneal stroma and gradually integrated with the surrounding tissue. These results indicate that gelatin based corneal scaffolds modified to absorb and release growth factors and seeded with HCECs, might be a suitable alternative for cadaveric cornea transplantation.Biomaterials 02/2014; 35(13). DOI:10.1016/j.biomaterials.2014.01.033 · 8.31 Impact Factor
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ABSTRACT: Collagen type I is a widely used natural biomaterial that has found utility in a variety of biological and medical applications. Its well-characterized structure and role as an extracellular matrix protein make it a highly relevant material for controlling cell function and mimicking tissue properties. Collagen type I is abundant in a number of tissues, and can be isolated as a purified protein. This review focuses on hydrogel biomaterials made by reconstituting collagen type I from a solubilized form, with an emphasis on in vitro studies in which collagen structure can be controlled. The hierarchical structure of collagen from the nanoscale to the macroscale is described, with an emphasis on how structure is related to function across scales. Methods of reconstituting collagen into hydrogel materials are presented, including molding of macroscopic constructs, creation of microscale modules and electrospinning of nanoscale fibers. The modification of collagen biomaterials to achieve the desired structures and functions is also addressed, with particular emphasis on mechanical control of collagen structure, creation of collagen composite materials and crosslinking of collagenous matrices. Biomaterials scientists have made remarkable progress in rationally designing collagen-based biomaterials and in applying them both to the study of biology and for therapeutic benefit. This broad review illustrates recent examples of techniques used to control collagen structure and thereby to direct its biological and mechanical functions.
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ABSTRACT: Keratoconus (KC) is a bilateral, asymmetric, corneal disorder that is characterized by progressive thinning, steepening, and potential scarring. The prevalence of KC is stated to be 1 in 2000 persons worldwide; however, numbers vary depending on size of the study and regions. KC appears more often in South Asian, Eastern Mediterranean, and North African populations. The cause remains unknown, although a variety of factors have been considered. Genetics, cellular, and mechanical changes have all been reported; however, most of these studies have proven inconclusive. Clearly, the major problem here, like with any other ocular disease, is quality of life and the threat of vision loss. While most KC cases progress until the third or fourth decade, it varies between individuals. Patients may experience periods of several months with significant changes followed by months or years of no change, followed by another period of rapid changes. Despite the major advancements, it is still uncertain how to treat KC at early stages and prevent vision impairment. There are currently limited tissue engineering techniques and/or "smart" biomaterials that can help arrest the progression of KC. This review will focus on current treatments and how biomaterials may hold promise for the future.09/2014; 5(3):111-34. DOI:10.3390/jfb5030111