Towards the development of osteochondral allografts with reduced immunogenicity.

Nowadays, repair and replacement of hyaline articular cartilage still challenges orthopedic surgery. Using a graft of decellularized articular cartilage as a structural scaffold is considered as a promising therapy. So far, successful cell removal has only been possible for small samples with destruction of the macrostructure or loss of biomechanics. Our aim was to develop a mild, enzyme-free chemical decellularization procedure while preserving the biomechanical properties of cartilage. Porcine osteochondral cylinders (diameter: 12 mm; height: 10 mm) were divided into four groups: Native plugs (NA), decellularized plugs treated with PBS, Triton-X-100 and SDS (DC), and plugs additionally treated with freeze-thaw-cycles of -20 °C, -80 °C or shock freezing in nitrogen (N2) before decellularization. In a non-decalcified HE stain the decellularization efficiency (cell removal, cell size, depth of decellularization) was calculated. For biomechanics the elastic and compression modulus, transition and failure strain as well as transition and failure stress were evaluated. The -20 °C, -80 °C, and N2 groups showed a complete decellularization of the superficial and middle zone. In the deep zone cells could not be removed in any experimental group. The biomechanical analysis showed only a reduced elastic modulus in all decellularized samples. No significant differences were found for the other biomechanical parameters.

Compressive behaviour of soft contact lenses and its effect on refractive power on the eye and handling off the eye.

PURPOSE: To investigate the stress-strain behaviour of 9 soft contact lens materials, that are commonly used in the market, under uniaxial compression loading. METHODS: Seven types of hydrogel and two types of silicone-hydrogel soft contact lens materials were hydrated in phosphate-buffered saline (PBS) solution then subjected to uniaxial compression loads. The load rate was set to 16.0 N/min starting with two consecutive initial 5.0 N loading cycles followed by three relaxation periods of 4.0 min within which there were two more 5.0 N loading cycles and eventually, a full loading cycle that stopped at a load of 49.0 N. The load and contraction data obtained experimentally were analysed to derive the stress-strain behaviour. Finite Element (FE) analysis was then utilised to evaluate the performance of soft contact lenses on the human eye and handling lenses off the eye. RESULTS: Unlike tensile tests, all tested materials showed nonlinear behaviour when tested under compression. When fitted to first-order Ogden hyperelastic model, parameter µ was found to be varying in the range 0.12 to 0.74 MPa and material parameter α was found to be varying in the range 8.2 to 20.326 among the nine tested materials. Compression modulus of elasticity was 2.2 times higher than the tensile modulus of elasticity on average. FE simulation with nonlinear Ogden constitutive model showed a limited change (8%~12%) in the optical performance when compared to other material models, however, it predicted higher stress when the lens was simulated under bending during off-eye handling. CONCLUSIONS: Compression tests revealed slightly nonlinear behaviour when materials were strained under compression stress down to 15% ~ 30% of their nominal heights. Considering the physiological compression loading range of 8 mmHg, secant moduli of elasticity were 1.5% to 6.9% higher than the tension moduli of elasticity depending on the material. Tensile-based moduli of elasticity could be used in FE analysis as a step towards simulating the optical performance of soft contact lenses on-eye. However, nonlinear compression-based material models are recommended for FE analysis of soft contact lenses when lens-handling is investigated off-eye.

Comparison of a fixed-grid and arbitrary Lagrangian-Eulerian methods on modelling fluid-structure interaction of the aortic valve.

This study was aimed at assessing the robustness of a fixed-grid fluid-structure interaction method (Multi-Material Arbitrary Lagrangian-Eulerian) to modelling the two-dimensional native aortic valve dynamics and comparing it to the Arbitrary Lagrangian-Eulerian method. For the fixed-grid method, the explicit finite element solver LS-DYNA was utilized, where two independent meshes for the fluid and structure were generated and the penalty method was used to handle the coupling between the fluid and structure domains. For the Arbitrary Lagrangian-Eulerian method, the implicit finite element solver ADINA was used where two separate conforming meshes were used for the valve structure and the fluid domains. The comparison demonstrated that both fluid-structure interaction methods predicted accurately the valve dynamics, fluid flow, and stress distribution, implying that fixed-grid methods can be used in situations where the Arbitrary Lagrangian-Eulerian method fails.

Clinical evaluation of a new correction algorithm for dynamic Scheimpflug analyzer tonometry before and after laser in situ keratomileusis and small-incision lenticule extraction.

PURPOSE: To compare a biomechanically corrected intraocular pressure (bIOP) algorithm provided by the dynamic Scheimpflug analyzer (Corvis ST) with Goldmann applanation tonometry IOP (Goldmann IOP) and standard dynamic Scheimpflug analyzer IOP measurements before and after laser in situ keratomileusis (LASIK) and refractive lenticule extraction small-incision lenticule extraction (SMILE) surgeries. SETTING: Smile Eye Clinic, Munich, Germany, and University of Liverpool, Liverpool, United Kingdom. DESIGN: Retrospective case series. METHODS: Patients scheduled for LASIK and patients scheduled for small-incision lenticule extraction for myopia or myopic astigmatism were included. The preoperative and postoperative evaluations included Goldmann, Scheimpflug tomography, and dynamic Scheimpflug analyzer IOP measurements. RESULTS: The study comprised 14 patients in the LASIK group and 22 patients in the small-incision lenticule extraction group. Preoperative Goldmann IOP and Scheimpflug analyzer IOP values showed significant positive correlation with central corneal thickness (CCT) (P = .05 for LASIK; P = .003 for small-incision lenticule extraction). No significant correlation was found between bIOP and CCT (P > .05). After both surgeries, there were significant decreases in Goldmann IOP (-3.2 mm Hg ± 3.4 [SD] and -3.2 ± 2.1 mm Hg, respectively; both P < .001) and Scheimpflug analyzer IOP (-3.7 ± 2.1 mm Hg and -3.3 ± 2.0 mm Hg, respectively, both P < .001) compared with preoperative readings, whereas bIOP did not differ significantly (0.1 ± 2.1 mm Hg and 0.8 ± 1.8 mm Hg, respectively; P = .80 and P = .273, respectively). CONCLUSIONS: The bIOP readings before and after LASIK and small-incision lenticule extraction were neither significantly different nor correlated with CCT. In contrast, both Goldmann IOP and Scheimpflug analyzer IOP had significant reductions postoperatively and showed significant correlation with CCT preoperatively.

Ex vivo testing of intact eye globes under inflation conditions to determine regional variation of mechanical stiffness.

BACKGROUND: The eye globe exhibits significant regional variation of mechanical behaviour. The aim of this present study is to develop a new experimental technique for testing intact eye globes in a form that is representative of in vivo conditions, and therefore suitable for determining the material properties of the complete outer ocular tunic. METHODS: A test rig has been developed to provide closed-loop control of either applied intra-ocular pressure or resulting apical displacement; measurement of displacements across the external surface of the eye globe using high-resolution digital cameras and digital image correlation software; prevention of rigid-body motion and protection of the ocular surface from environmental drying. The method has been demonstrated on one human and one porcine eye globe, which were cyclically loaded. Finite element models based on specimen specific tomography, free from rotational symmetry, were used along with experimental pressure-displacement data in an inverse analysis process to derive the mechanical properties of tissue in different regions of the eye's outer tunic. RESULTS: The test method enabled monitoring of mechanical response to intraocular pressure variation across the surface of the eye globe. For the two eyes tested, the method showed a gradual change in the sclera's stiffness from a maximum at the limbus to a minimum at the posterior pole, while in the cornea the stiffness was highest at the centre and lowest in the peripheral zone. Further, for both the sclera and cornea, the load-displacement behaviour did not vary significantly between loading cycles. CONCLUSIONS: The first methodology capable of mechanically testing intact eye globes, with applied loads and boundary conditions that closely represent in vivo conditions is introduced. The method enables determination of the regional variation in mechanical behaviour across the ocular surface.

Development and validation of a correction equation for Corvis tonometry.

PRIMARY OBJECTIVE: This study uses numerical analysis and validation against clinical data to develop a method to correct intraocular pressure (IOP) measurements obtained using the Corvis Tonometer for the effects of central corneal thickness (CCT), and age. MATERIALS AND METHODS: Finite element analysis was conducted to simulate the effect of tonometric air pressure on the intact eye globe. The analyses considered eyes with wide variations in IOP (10-30 mm Hg), CCT (445-645 microns), R (7.2-8.4 mm), shape factor, P (0.6-1) and age (30-90 years). In each case, corneal deformation was predicted and used to estimate the IOP measurement by Corvis (CVS-IOP). Analysis of the results led to an algorithm relating estimates of true IOP as a function of CVS-IOP, CCT and age. All other parameters had negligible effect on CVS-IOP and have therefore been omitted from the algorithm. Predictions of corrected CVS-IOP, as obtained by applying the algorithm to a clinical data-set involving 634 eyes, were assessed for their association with the cornea stiffness parameters; CCT and age. RESULTS: Analysis of CVS-IOP measurements within the 634-large clinical data-set showed strong correlation with CCT (3.06 mm Hg/100 microns, r(2) = 0.204) and weaker correlation with age (0.24 mm Hg/decade, r(2) = 0.009). Applying the algorithm to IOP measurements resulted in IOP estimations that became less correlated with both CCT (0.04 mm Hg/100 microns, r(2) = 0.005) and age (0.09 mm Hg/decade, r(2) = 0.002). CONCLUSIONS: The IOP correction process developed in this study was successful in reducing reliance of IOP measurements on both corneal thickness and age in a healthy European population.

Multiphysics simulation of the effect of leaflet thickness inhomogeneity and material anisotropy on the stress-strain distribution on the aortic valve.

This study developed a realistic 3D FSI computational model of the aortic valve using the fixed-grid method, which was eventually employed to investigate the effect of the leaflet thickness inhomogeneity and leaflet mechanical nonlinearity and anisotropy on the simulation results. The leaflet anisotropy and thickness inhomogeneity were found to significantly affect the valve stress-strain distribution. However, their effect on valve dynamics and fluid flow through the valve were minor. Comparison of the simulation results against in-vivo and in-vitro data indicated good agreement between the computational models and experimental data. The study highlighted the importance of simulating multi-physics phenomena (such as fluid flow and structural deformation), regional leaflet thickness inhomogeneity and anisotropic nonlinear mechanical properties, to accurately predict the stress-strain distribution on the natural aortic valve.

Assessment of the Ocular Response Analyzer as an Instrument for Measurement of Intraocular Pressure and Corneal Biomechanics.

PURPOSE: The purpose of this study is to provide better understanding of the Ocular Response Analyzer (ORA) and how reliable it is to produce intraocular pressure (IOP) measurements that are free of the effects of corneal stiffness parameters, and stiffness estimates that are independent of IOP. MATERIALS AND METHODS: A numerical parametric study that closely represents the in-vivo conditions of the human eye and the ORA procedure was conducted to determine the correlation coefficient r(2) between ORA output and the values of true IOP and a number of stiffness parameters, namely corneal thickness, curvature and age. For the purpose of this exercise, the ORA output was put in the form k1P1+k2P2 where k1 and k2 were variables and P1 and P2 were ORA's measured applanation pressures. Two separate clinical datasets involving Moorfields Eye Hospital, London and the University of New South Wales, Sydney participants, respectively, were used to validate the numerical results. RESULTS: The numerical study results show a strong association between (k1P1 + k2P2) and the true IOP over a wide range of k1 and k2 values apart from a narrow region approximately extending from (k1 = +2, k2 = -2) to (k1 = -2, k2 = +2). On the other hand, (k1· P1 + k2· P2) was found to have a strong association with CCT, R and age (the stiffness parameters) over the same narrow region, beyond which the association was weak. Similar trends were found with the two clinical datasets. CONCLUSIONS: The results of this study show the potential of the ORA to provide reliable IOP measurements with weak dependence on the cornea's stiffness parameters and the considerably reduced reliability in producing stiffness estimates that are unaffected by IOP values.

Influence of glucocorticosteroids on the biomechanical properties of in-vivo rabbit cornea.

Understanding corneal biomechanical responses during long-term glucocorticosteroids administration is important in clinical practice. The purpose of this study is to investigate the biomechanical influence of fluorometholone 0.1% eye drops on rabbit cornea. Thirty-eight Japanese white rabbits were randomly divided into three groups; a fluorometholone group, a supernatant group and a blank control group. For each rabbit in fluorometholone group, one cornea was treated with fluorometholone 0.1% eye drops four times a day for 8 weeks, while corneas of rabbits in supernatant group were treated in the same frequency with supernatant fraction centrifuged from fluorometholone 0.1% eye drops. The rabbits in the blank control group were not given any treatment. At the end of the 8 week observation period, the rabbits were euthanized and the eyes immediately enucleated and prepared for inflation testing. The experimental pressure-deformation data was used to derive the stress-strain behavior of each eye using an inverse modeling procedure. Comparisons of mechanical stiffness of corneas were conducted among the three groups to determine the influence of fluorometholone. The results showed that corneal stiffness decreased as the fluorometholone administration time prolonged. Comparisons of tangent modulus indicated average stiffness reductions of 34.2% and 33.5% in the fluorometholone group compared to the supernatant and control groups, respectively, at the end of the observation period. The stiffness-reduction effect of fluorometholone on the cornea should be considered in clinical management, especially when administrating it to biomechanically weakened corneas, such as after refractive surgeries and in cases of keratoconus.

Stress free configuration of the human eye.

Numerical simulations of eye globes often rely on topographies that have been measured in vivo using devices such as the Pentacam or OCT. The topographies, which represent the form of the already stressed eye under the existing intraocular pressure, introduce approximations in the analysis. The accuracy of the simulations could be improved if either the stress state of the eye under the effect of intraocular pressure is determined, or the stress-free form of the eye estimated prior to conducting the analysis. This study reviews earlier attempts to address this problem and assesses the performance of an iterative technique proposed by Pandolfi and Holzapfel [1], which is both simple to implement and promises high accuracy in estimating the eye's stress-free form. A parametric study has been conducted and demonstrated reliance of the error level on the level of flexibility of the eye model, especially in the cornea region. However, in all cases considered 3-4 analysis iterations were sufficient to produce a stress-free form with average errors in node location <10(-6)mm and a maximal error <10(-4)mm. This error level, which is similar to what has been achieved with other methods and orders of magnitude lower than the accuracy of current clinical topography systems, justifies the use of the technique as a pre-processing step in ocular numerical simulations.