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      The Mechanical Interpretation of Ocular Response Analyzer Parameters

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          Abstract

          Purpose

          Ocular Response Analyzer (ORA) is one of the most widely used devices in clinic, while the mechanical interpretations of parameters obtained from ORA have not been understood completely. The aim of this research is to explore the mechanical interpretation of ORA parameters.

          Methods

          Rabbits aged 3-24 months were measured with ORA in vivo and corneal strips uniaxial tensile tests to get ORA parameters and corneal biomechanical parameters (corneal elastic modulus, relaxation time, and relaxation limit). The mechanical interpretation of ORA parameters was cognized preliminarily by analyzing the correlation between ORA parameters and corneal biomechanical parameters. On the other hand, finite element method was applied to simulate ORA measurements with different corneal biomechanical parameters to obtain quantitative relationship between ORA parameters and corneal biomechanical parameters further.

          Results

          Biomechanical experimental results showed that Corneal Resistance Factor (CRF) was correlated with corneal elastic modulus and relaxation limit significantly, while the significant correlations between Corneal Hysteresis (CH) and corneal biomechanical parameters were not observed. Results of finite element analysis showed that both CH and CRF were correlated with corneal elastic modulus, relaxation limit, and relaxation time significantly. Besides, corneal elastic modulus was positively correlated with upslop1 and upslop2 and negatively correlated with w2.

          Conclusions

          For all ORA parameters, CH, CRF, the upslope, and the width of the peaks are parameters which may reflect corneal elastic properties. It is viable to cognize mechanical interpretation of ORA parameters by the comparisons of the data from ORA and biomechanical tests of rabbits with different ages and the simulations of ORA based on finite element methods. Further studies are needed to confirm the mechanical interpretation.

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          Most cited references34

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          Strain-enhanced stress relaxation impacts nonlinear elasticity in collagen gels

          The extracellular matrix is a complex assembly of structural proteins that provides physical support and biochemical signaling to cells within our tissues. One of the key structural components of the extracellular matrix is collagen, and matrices of collagen exhibit remarkable mechanical properties. Their resistance to deformation is enhanced as deformation is increased over short timescales, a behavior termed strain stiffening, yet they exhibit some characteristics of viscous fluids at longer timescales. Strikingly, we show that the strain stiffening of collagen matrices is coupled with their liquid-like behavior: at greater deformations, these matrices become stiffer but then flow more rapidly to relax this increase in stiffness. These complex mechanical behaviors are likely to be relevant to cellular interactions with these matrices. The extracellular matrix (ECM) is a complex assembly of structural proteins that provides physical support and biochemical signaling to cells in tissues. The mechanical properties of the ECM have been found to play a key role in regulating cell behaviors such as differentiation and malignancy. Gels formed from ECM protein biopolymers such as collagen or fibrin are commonly used for 3D cell culture models of tissue. One of the most striking features of these gels is that they exhibit nonlinear elasticity, undergoing strain stiffening. However, these gels are also viscoelastic and exhibit stress relaxation, with the resistance of the gel to a deformation relaxing over time. Recent studies have suggested that cells sense and respond to both nonlinear elasticity and viscoelasticity of ECM, yet little is known about the connection between nonlinear elasticity and viscoelasticity. Here, we report that, as strain is increased, not only do biopolymer gels stiffen but they also exhibit faster stress relaxation, reducing the timescale over which elastic energy is dissipated. This effect is not universal to all biological gels and is mediated through weak cross-links. Mechanistically, computational modeling and atomic force microscopy (AFM) indicate that strain-enhanced stress relaxation of collagen gels arises from force-dependent unbinding of weak bonds between collagen fibers. The broader effect of strain-enhanced stress relaxation is to rapidly diminish strain stiffening over time. These results reveal the interplay between nonlinear elasticity and viscoelasticity in collagen gels, and highlight the complexity of the ECM mechanics that are likely sensed through cellular mechanotransduction.
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            Biomechanical properties of human and porcine corneas.

            The suitability of porcine corneas as approximate models for human corneas in mechanical property characterisation studies is experimentally assessed. Thirty seven human donor corneas and thirty four ex-vivo porcine corneas were tested under inflation conditions to determine their short-term stress-strain behaviour and long-term creep behaviour up to 2.8 h (10,000 s). Vertical strips extracted from further 12 human corneas and 10 porcine corneas were subjected to stress-relaxation tests for up to 20 min at different stress levels. Human and porcine corneas were observed to have almost the same form of behaviour under short and long-term loading. They both exhibited non-linear stress-strain behaviour and reacted to sustained loading in a similar fashion. However, human corneas were significantly stiffer than porcine corneas. They also crept less under long-term loading and could sustain their stress state for longer compared to porcine corneas. These differences, in addition to others identified earlier in relation to corneal mechanical anisotropy, cast doubt on the suitability of porcine corneas as models for human corneas in mechanical studies.
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              Comparative study of corneal strip extensometry and inflation tests.

              Strip extensometry tests are usually considered less reliable than trephinate inflation tests in studying corneal biomechanics. In spite of the evident simplicity of strip extensometry tests, several earlier studies preferred inflation tests in determining the constitutive relationship of the cornea and its other material properties, such as Young's modulus and the hysteresis behaviour. In this research, the deficiencies of the strip tests are discussed and a mathematical procedure presented to take account of these deficiencies when obtaining the corneal material properties. The study also involves testing 10 pairs of porcine corneas using both strip extensometry and trephinate inflation techniques and the results are subjected to mathematical back analysis in order to determine the stress-strain behaviour. The behaviour obtained from the strip extensometry tests and using the new mathematical analysis procedure is shown to match closely the inflation test results.
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                Author and article information

                Contributors
                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2019
                16 July 2019
                : 2019
                : 5701236
                Affiliations
                1Beijing Key Laboratory of Fundamental Research on Biomechanics in Clinical Application, Capital Medical University, Beijing 100069, China
                2School of Biomedical Engineering, Capital Medical University, Beijing 100069, China
                Author notes

                Academic Editor: Juan M. Bueno

                Author information
                https://orcid.org/0000-0001-5489-5987
                https://orcid.org/0000-0002-9190-5475
                Article
                10.1155/2019/5701236
                6662474
                31380431
                2034b682-baf9-474a-9f81-74e1860fa5e1
                Copyright © 2019 Xiao Qin et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 January 2019
                : 3 June 2019
                : 20 June 2019
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 31370952
                Award ID: 31470914
                Categories
                Research Article

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