Numerical studies on Corneal Biomechanics and development of Silica-Collagen Corneal hybrids

Abstract

Human cornea exhibits viscoelastic behavior as in other living tissues. The cornea is mainly dominated by the stroma which constitutes 90% of the corneal thickness. A number of experiments on tensile strip of human bovine corneas show that the tissue exhibits anisotropic, non-linear, rate dependent, viscoelastic mechanical stress-strain response and also a highly nonlinear creep response that depends on the applied stress. The work comprises two different areas; the first one is related to mathematical modeling of viscoelsticity of cornea. The second part is related to development of corneal substitute. The first phase of the work is a computational analysis of a blunt body impact on corneal viscoelastic behavior; simultaneously comparison is drawn between the tissue behaviors with corresponding cases considering the tissue to be elastic in other simulated model. A simulation model of eye is set up based on the information of cadaver eyes done in the earlier works in this domain. Three dimensional models of corneal tissue were subjected to blunt body impact at different velocities in ALTAIR platform to study the nature of injury on the tissue material. The variation in the strain due to impact on the cornea for the material behaviors, range in the order 10-2±0.002 and that for the stress, the magnitude gets almost double for elastic nature of cornea. The results shows that the viscoelastic biomechanics of the tissue predict higher resistance to any foreign body impacting on the surface of cornea preventing it from further indentation into the tissue. The viscoelastic model provided in this work can be incorporated for the synthesis of artificial corneas and soft contact lenses. A mathematical approach has been taken further in this work to trace out the rate dependent, anisotropic and viscoelastic response. Two basic classical models have been taken into account to compare and predict the rate dependent response. On one hand as the K-V Model shows similar nature, Maxwell Model violates the same with a large discrepancy and thus giving rise to the Fractional operator FMM. Fractional calculus approach has hence been taken into account in modeling human corneal viscoelastic behavior. The degree of both elasticity and viscosity is much convenient to consider when described in terms of the fractional order parameters. FMM plays an essential role to study viscoelastic properties. This paper presents modeling of the human cornea when subjected to simple stress in the order of few MN/m2 by FMM. The governing fractional equation involving two fractional parameters α and β have been considered to model the stress-strain relationship of human cornea. The analytical solution of the fractional equation has been obtained for values of α and β using Laplace transform methods. The effect of the fractional parameter values on the stress-deformation nature has been observed and studied. A comparison between experimental values and computational values for the various fractional order of the Maxwell model equation clearly describes the mathematical model of choroidal and scleral strips and also shows range of values of the parameters for which the mathematical model depicts the real time stress-strain relationship of human cornea. It can also be seen that this model concludes to the Classical Maxwell model as a special case for α = β = 1 and that human eye does not clearly obey the Maxwell model viscoelastic property. The experimental part of the study is mainly focused on the synthesis and development of Silica-Collagen Hybrids that can substitute normal healthy cornea of human. The main issue that concerns the patients and doctors after a donor corneal transplant is Auto-Immune Rejection by host body which may be due to biocompatibility, haemocompatibility or cytotoxicity. The research thrives for synthesis of a composite comprised of Collagen, the basic protein that can be abundantly found in human body and silica which is biosafe and biocompatible to physiological system and can act as a scaffold for tissue engineering and drug delivery. The starting materials of the synthesis are diluted Silica precursor and two types of collagen-I and III which is predominantly found on the epithelium and basement membrane of the cornea. Sol Gel technique has been applied for the synthesis of the composite and finally lyophilized after the pH has been stabilized around 7.2-7.4 to obtain dehydrated silica collagen composite. Optical property of the developed composite closely mimics the collagen hybrids from earlier work in this field. The composite exhibits crystallinity as it evidenced from its XRD plot. Other material characterizations, viz. FTIR and SEM have been performed on the sample to identify the nature of the composite. Despite significant advance in the research front, one of the major concern is the price of commercial collagen and unavailability of indigenous components. This is the reason which has given path to extraction of nascent collagen from fish skin in this research. Sperata Aor, commonly known as Indian Catfish has a thick layer of epidermal tissue which is a reserve of basic protein, collagen and fats. The objective of the work is to extract the collagen present in the skin. The skin has been carefully removed and treated with stock solution to loosen the non-protein bonds and further treated with butyl alcohol to remove fats. To loosen the thick fibres of the skin it is finally suspended in acetic acid and finally filtered and washed with deionized water followed by centrifugation and salting. Salting helps to remove any traces of acetic acid and finally pH has been maintained and lyophilized for 48hours in -60oC which lead to a porous spongy mesh of collagen. The presence of Amide A and Amide I&II confirms the material thus extracted is predominantly collagen type I. SEM images has shown fibrillar structures with some knotted structure which also confirms it to be Collagen. This collagen can be used for preparation of tissue engineering scaffolds and for development of Biomimetic structure exhibiting both physiological and electrical properties. In conclusion the studies in the thesis has been organized under three major sections which have given better understanding on the physiology and biomechanical behavior of the delicate tissue whose damage may cause severe injury and even death sometimes. Through the experimental investigation an insight has been developed about Sol-Gel technique and the property and structure of the collagen protein for possible application in drug delivery and tissue engineering.