J. Funct. Biomater.2015, 6(3), 963-985; doi:10.3390/jfb6030963 - published 21 September 2015 Show/Hide Abstract
Abstract: Among ocular pathologies, glaucoma is the second leading cause of progressive vision loss, expected to affect 80 million people worldwide by 2020. A primary cause of glaucoma appears to be damage to the conventional outflow tract. Conventional outflow tissues, a composite of the trabecular meshwork and the Schlemm’s canal, regulate and maintain homeostatic responses to intraocular pressure. In glaucoma, filtration of aqueous humor into the Schlemm’s canal is hindered, leading to an increase in intraocular pressure and subsequent damage to the optic nerve, with progressive vision loss. The Schlemm’s canal encompasses a unique endothelium. Recent advances in culturing and manipulating Schlemm’s canal cells have elucidated several aspects of their physiology, including ultrastructure, cell-specific marker expression, and biomechanical properties. This review highlights these advances and discusses implications for engineering a 3D, biomimetic, in vitro model of the Schlemm’s canal endothelium to further advance glaucoma research, including drug testing and gene therapy screening.
J. Funct. Biomater.2015, 6(3), 946-962; doi:10.3390/jfb6030946 - published 16 September 2015 Show/Hide Abstract
Abstract: Bombyx mori silk fibroin membranes provide a potential delivery vehicle for both cells and extracellular matrix (ECM) components into diseased or injured tissues. We have previously demonstrated the feasibility of growing retinal pigment epithelial cells (RPE) on fibroin membranes with the view to repairing the retina of patients afflicted with age-related macular degeneration (AMD). The goal of the present study was to investigate the feasibility of incorporating the ECM component elastin, in the form of human recombinant tropoelastin, into these same membranes. Two basic strategies were explored: (1) membranes prepared from blended solutions of fibroin and tropoelastin; and (2) layered constructs prepared from sequentially cast solutions of fibroin, tropoelastin, and fibroin. Optimal conditions for RPE attachment were achieved using a tropoelastin-fibroin blend ratio of 10 to 90 parts by weight. Retention of tropoelastin within the blend and layered constructs was confirmed by immunolabelling and Fourier-transform infrared spectroscopy (FTIR). In the layered constructs, the bulk of tropoelastin was apparently absorbed into the initially cast fibroin layer. Blend membranes displayed higher elastic modulus, percentage elongation, and tensile strength (p < 0.01) when compared to the layered constructs. RPE cell response to fibroin membranes was not affected by the presence of tropoelastin. These findings support the potential use of fibroin membranes for the co-delivery of RPE cells and tropoelastin.
J. Funct. Biomater.2015, 6(3), 917-945; doi:10.3390/jfb6030917 - published 11 September 2015 Show/Hide Abstract
Abstract: Corneal endothelium is a single layer of specialized cells that lines the posterior surface of cornea and maintains corneal hydration and corneal transparency essential for vision. Currently, transplantation is the only therapeutic option for diseases affecting the corneal endothelium. Transplantation of corneal endothelium, called endothelial keratoplasty, is widely used for corneal endothelial diseases. However, corneal transplantation is limited by global donor shortage. Therefore, there is a need to overcome the deficiency of sufficient donor corneal tissue. New approaches are being explored to engineer corneal tissues such that sufficient amount of corneal endothelium becomes available to offset the present shortage of functional cornea. Although human corneal endothelial cells have limited proliferative capacity in vivo, several laboratories have been successful in in vitro expansion of human corneal endothelial cells. Here we provide a comprehensive analysis of different substrates employed for in vitro cultivation of human corneal endothelial cells. Advances and emerging challenges with ex vivo cultured corneal endothelial layer for the ultimate goal of therapeutic replacement of dysfunctional corneal endothelium in humans with functional corneal endothelium are also presented.
J. Funct. Biomater.2015, 6(3), 901-916; doi:10.3390/jfb6030901 - published 10 September 2015 Show/Hide Abstract
Abstract: The outstanding combination of high tensile strength and extensibility of spider silk is believed to contribute to the material’s toughness. Thus, there is great interest in engineering silk for biomedical products such as suture or implants. Additionally, over the years, many studies have also sought to enhance the mechanical properties of spider silk for wider applicability, e.g., by irradiating the material using ultra-violet radiation. However, the limitations surrounding the use of ultra-violet radiation for enhancing the mechanical properties of spider silk are not well-understood. Here, we have analyzed the mechanical properties of spider silk at short ultra-violet irradiation duration. Specimens of spider silk were subjected to ultra-violet irradiation (254-nm wavelength, i.e. UVC) for 10, 20, and 30 min, respectively, followed by tensile test to rupture to determine the strength (maximum stress), extensibility (rupture strain), and toughness (strain energy density to rupture). Controls, i.e., specimens that did not received UVC, were also subjected to tensile test to rupture to determine the respective mechanical properties. One-way analysis of variance reveals that these properties decrease significantly (p < 0.05) with increasing irradiation duration. Among the three mechanical parameters, the strength of the spider silk degrades most rapidly; the extensibility of the spider silk degrades the slowest. Overall, these changes correspond to the observed surface modifications as well as the bond rupture between the peptide chains of the treated silk. Altogether, this simple but comprehensive study provides some key insights into the dependence of the mechanical properties on ultra-violet irradiation duration.
J. Funct. Biomater.2015, 6(3), 889-900; doi:10.3390/jfb6030889 - published 8 September 2015 Show/Hide Abstract
Abstract: Since polyethylene is one of the most frequently used biomaterials, such as in bearing components in joint arthroplasty, strong efforts have been made to improve the design and material properties over the last decades. Antioxidants, such as vitamin-E, seem to be a promising alternative to further increase durability and reduce polyethylene wear and degradation in the long-term. Nevertheless, even if several promising in vitro results are available, there is yet no clinical evidence that vitamin-E polyethylenes show these advantages in vivo. The aim of this paper was to provide a comprehensive overview on the current knowledge regarding the biological and mechanical proprieties of this biomaterial, underlying the in vitro and in vivo evidence for effectiveness of vitamin-E-doped polyethylene in joint arthroplasty.
J. Funct. Biomater.2015, 6(3), 863-888; doi:10.3390/jfb6030863 - published 28 August 2015 Show/Hide Abstract
Abstract: The cornea is essential for normal vision by maintaining transparency for light transmission. Limbal stem cells, which reside in the corneal periphery, contribute to the homeostasis of the corneal epithelium. Any damage or disease affecting the function of these cells may result in limbal stem cell deficiency (LSCD). The condition may result in both severe pain and blindness. Transplantation of ex vivo cultured cells onto the cornea is most often an effective therapeutic strategy for LSCD. The use of ex vivo cultured limbal epithelial cells (LEC), oral mucosal epithelial cells, and conjunctival epithelial cells to treat LSCD has been explored in humans. The present review focuses on the current state of knowledge of the many other cell-based therapies of LSCD that have so far exclusively been explored in animal models as there is currently no consensus on the best cell type for treating LSCD. Major findings of all these studies with special emphasis on substrates for culture and transplantation are systematically presented and discussed. Among the many potential cell types that still have not been used clinically, we conclude that two easily accessible autologous sources, epidermal stem cells and hair follicle-derived stem cells, are particularly strong candidates for future clinical trials.