The vitreous humor is a fragile, transparent hydrogel between the lens and the retina that liquefies with age, causing complications such as cataract formation, retinal detachment, and macular hole, sometimes necessitating surgical replacement with a substitute. Current clinical and experimental vitreous substitutes are inadequate since they do not address the problem of oxidative damage after the removal and replacement of the natural vitreous. In fact, up to 95% of patients require cataract extraction within 24 months after vitrectomy. There is a clear clinical need for a new generation of biomimetic vitreous substitutes that can replace not only the physical roles but also chemical functions of the natural vitreous humor. The objective of this project was to create an antioxidant releasing hydrogel as a vitreous substitute. This hydrogel must adequately provide the mechanical functions and have similar material properties as the natural human vitreous. Additionally, the hydrogel must have the potential to mitigate the oxidative damage in the eye post-vitrectomy and potentially reestablish the natural oxygen gradient in the vitreous.
The vitreous humor of the eye is a biological hydrogel principally composed of fibrillary collagen interspersed with semi-flexible polyelectrolyte, hyaluronic acid (HA). Certain pathological conditions necessitate its removal and replacement. Current vitreous substitutes, such as silicone oils and perfluorocarbons, are hydrophobic, do not resemble the properties of the vitreous, and have known complications. An ideal vitreous substitute should have properties of the natural vitreous, perform its functions, and be biocompatible in the eye. Inspired by the structure and composition of the natural vitreous, we used bio-mimicry to develop an injectable two-component hydrogel. The hydrogel is composed of a fibrillary gellan, an analogue of collagen, and a semi-flexible polyelectrolyte poly[methacrylamide-co-(methacrylic acid)], an analogue of hyaluronic acid, both endowed with thiol cross-linkers for reversible covalent linkage. The gellan, in the polymeric mixture, undergoes coil-helix transition near physiological temperature, enabling instantaneous in situ physical gelation of the solution. The thiol cross-linkers that later oxidize to disulfides under physiological conditions, make the hydrogel non-absorbable, non-degradable, and reversible, for facile removal if needed.We used response surface methodology to investigate the structure-property relationships of eleven two-component hydrogels, and identified two hydrogel formulations that match the primary properties of the vitreous. We determined how each component of the hydrogel affects their optical, mechanical, sol-gel transition temperature, and osmotic swelling properties. All the hydrogels were transparent to visible light, with density and refractive indexes nearly equivalent to those of the natural vitreous. The shear storage moduli of the hydrogels, at 1Hz, ranged from 3 to 358 Pa, and the sol-gel transition temperatures, from 35.5 to 43 °C. In addition, as expected, all the hydrogels swelled in physiological solutions. Interestingly, we discovered that the relatively large swelling capacity of the semi-flexible ionic copolymer was significantly restricted by the minimally swellable fibrillary gellan network. The tightly swollen gel of two dissimilar networks produced Donnan osmotic swelling pressure in physiological solutions, which is also the driving force for re-attachment of the retina. Insights from the biomimetic nature of the gel, led us to propose that the natural vitreous also exhibits controlled swelling, where ionic HA's swelling capacity is restricted by fibrillary collagen. The Donnan swelling pressure produced by the tightly swollen vitreous gel maintains the delicate internal structure of the eye, and perhaps plays a critical role during the ocular development.We evaluated the biocompatibility of the two optimized formulations of the hydrogels on different cell lines, and in rabbits. Both hydrogels were found to be biocompatible on primary porcine retinal pigment epithelial cells, human retinal pigment epithelial cells, and fibroblast (3T3/NIH) cells, by electric cell-substrate impedance sensing system. Furthermore, the hydrogels did not impair tight junction formation or affect proliferation of the cells. The hydrogels were also non-degradable in enzymatic solutions and in contact with ocular cell line for four weeks. Judged against silicone oil, a clinically-accepted vitreous replacement, both hydrogel formulations were biocompatible in rabbits for 30 days. Both hydrogels maintained optical clarity, physiological intra-ocular pressure, and intact retinal layers that displayed normal electroretinographs. In two cases of the iatrogenic retinal tear, the hydrogels reattached the retina by producing osmotic swelling pressure. The hydrogels also maintained the low oxygen environment, compared to silicone oil, in the rabbit's vitreous cavity for 30 days post-surgery.In conclusion, the two hydrogels reattach the retina via a unique mechanism of osmotic swelling pressure. They overcome the limitations of silicone oil with comparable in-vivo biocompatibility, and merit further evaluations as an artificial vitreous. In addition, the ability to control the mechanical and swelling properties of the two-component hydrogels over a wide range suggests their utility as biomimetic replacements of other soft tissues, such as cornea, nucleus pulposus, and cartilage.
This book provides tabular and text data relating to normal and diseased tissue materials and materials used in medical devices. Comprehensive and practical for students, researchers, engineers, and practicing physicians who use implants, this book considers the materials aspects of both implantable materials and natural tissues and fluids. Examples of materials and topics covered include titanium, elastomers, degradable biomaterials, composites, scaffold materials for tissue engineering, dental implants, sterilization effects on material properties, metallic alloys, and much more. Each chapter author considers the intrinsic and interactive properties of biomaterials, as well as their appropriate applications and historical contexts. Now in an updated second edition, this book also contains two new chapters on the cornea and on vocal folds, as well as updated insights, data, and citations for several chapters.
With an increasingly aged population, eye diseases are becoming more widespread. Biomaterials have contributed in recent years to numerous medical devices for the restoration of eyesight, improving many patients’ quality of life. Consequently, biomaterials and regenerative medicine are becoming increasingly important to the advances of ophthalmology and optometry. Biomaterials and regenerative medicine in ophthalmology reviews the present status and future direction of biomaterials and regenerative medicine in this important field.Part one discusses applications in the anterior segment of the eye with chapters on such topics as advances in intraocular lenses (IOLs), synthetic corneal implants, contact lenses, and tissue engineering of the lens. Part two then reviews applications in the posterior segment of the eye with such chapters on designing hydrogels as vitreous substitutes, retinal repair and regeneration and the development of tissue engineered membranes. Chapters in Part three discuss other pertinent topics such as hydrogel sealants for wound repair in ophthalmic surgery, orbital enucleation implants and polymeric materials for orbital reconstruction.With its distinguished editor and international team of contributors, Biomaterials and regenerative medicine in ophthalmology is a standard reference for scientists and clinicians, as well as all those concerned with this ophthalmology. Reviews the increasingly important role of biomaterials and regenerative medicine in the advancement of ophthalmology and optometry Provides an overview of the present status and future direction of biomaterials and regenerative medicine in this important field Discusses applications in both the anterior and prosterior segments of the eye with chapters on such topics as synthetic corneal implants and retinal repair and regeneration
Biodegradable thermogels are a promising class of stimuli-responsive polymers. This book summarizes recent developments in thermogel research with a focus on synthesis and self-assembly mechanisms, gel biodegradability, and applications for drug delivery, cell encapsulation and tissue engineering. A closing chapter on commercialisation shows the challenges faced bringing this new material to market. Edited by leading authorities on the subject, this book offers a comprehensive overview for academics and professionals across polymer science, materials science and biomedical and chemical engineering.
The spectral transmittance of ultraviolet, visible, and near infrared light through the ocular media of humans has been measured. Using freshly enucleated eyes, the transmittances of each component part (cornea, aqueous humor, lens, vitreous humor) were determined for the wavelength range from 0.22 to 2.8 microns. To date 9 eyes have been measured, ranging in age from 4 weeks to 75 years. Two types of measurements were made: the first to measure the total light transmitted (direct and scattered) at each wavelength and the second to measure the percent transmittance of that light passing directly through the various media without absorption or scattering. The results show that: (a) the transmission of ultraviolet radiation decreases with the age of the eye; (b) the transmission of infrared radiation appears to be independent of the age; and (c) the maximum total transmittance of the whole eye, about 81 percent, is obtained in the region from 600 to 850 millimicrons.
This first book on nanocellulose and nanohydrogels for biomedical applications is unique in discussing recent advancements in the field, resulting in a comprehensive, well-structured overview of nanocellulose and nanohydrogel materials based nanocomposites. The book covers different types of nanocellulose materials and their recent developments in the drug delivery and nanomedicine sector, along with synthesis, characterization, as well as applications in the biotechnological and biomedical fields. The book also covers the current status and future perspectives of bacterial cellulose and polyester hydrogel matrices, their preparation, characterization, and tissue engineering applications of water soluble hydrogel matrices obtained from biodegradable sources. In addition, the chitosan-based hydrogel and nanogel matrices, their involvement in the current biofabrication technologies, and influencing factors towards the biomedical sector of biosensors, biopharmaceuticals, tissue engineering appliances, implant materials, diagnostic probes and surgical aids are very well documented. Further, the history of cellulose-based and conducting polymer-based nanohydrogels, their classification, synthesis methods and applicability to different sectors, the challenges associated with their use, recent advances on the inhibitors of apoptosis proteins are also included. The recent developments and applications in the drug delivery sector gives an overview of facts about the nanofibrillated cellulose and copoly(amino acid) hydrogel matrices in the biotechnology and biomedicine field. This book serves as an essential reference for researchers and academics in chemistry, pharmacy, microbiology, materials science and biomedical engineering.
