Victor H. Barocas

Engineered Alignment in Media Equivalents: Magnetic Prealignment and Mandrel Compaction

We predicted and measured the evolution of smooth muscle cell (SMC) orientation in media-equivalents (MEs) for four fabrication conditions (F-, M-, F+, M+) under Free or Mandrel compaction (F/M) with and without magnetic prealignment of the collagen fibrils in the circumferential direction (+/-). Mandrel compaction refers to SMC-induced compaction of the ME that is constrained by having a nonadhesive mandrel placed in the ME lumen. Predictions were made using our anisotropic biphasic theory (ABT) for tissue-equivalent mechanics. Successful prediction of trends of the SMC orientation data for all four fabrication cases was obtained: maintenance of the initial isotropic state for F-, loss of initial circumferential alignment for F+, development of circumferential alignment for M-, and enhancement of initial circumferential alignment for M+. These results suggest two mechanisms by which the presence of the mandrel leads to much greater mechanical stiffness in the circumferential direction reported for mandrel compacted MEs relative to free compacted MEs: (1) by inducing an increasing circumferential alignment of the SMC and collagen, and (2) by inducing a large stress on the SMC, resulting in secretion and accumulation of stiffening components.

Permeability and diffusion in vitreous humor: implications for drug delivery.

AbstractPurpose. Previous experimental work suggests that convection maybe important in determining the biodistribution of drugs implanted orinjected in the vitreous humor. To develop accurate biodistributionmodels, the relative importance of diffusion and convection inintravitreal transport must be assessed. This requires knowledge of both thediffusivity of candidate drugs and the hydraulic conductivity of thevitreous humor.nMethods. Hydraulic conductivity of cadaveric bovine vitreous humorwas measured by confined compression tests at constant loads of 0.15and 0.2 N and analyzed numerically using a two-phase model. Diffusioncoefficient of acid orange 8, a model compound, in the same mediumwas measured in a custom-built diffusion cell.nResults. Acid orange 8 diffusivity within vitreous humor is about halfthat in free solution. When viscous effects are properly accounted for,the hydraulic conductivity of bovine vitreous humor is 8.4 ± 4.5 ×10−7 cm2/Pa s.nConclusions. We predict that convection does not contributesignificantly to transport in the mouse eye, particularly forlow-molecular-weight compounds. For delivery to larger animals, such as humanswe conclude that convection accounts for roughly 30% of the totalintravitreal drug transport. This effect should be magnified forhigher-molecular-weight compounds, which diffuse more slowly, and inglaucoma, which involves higher intraocular pressure and thus potentiallyfaster convective flow. Thus, caution should be exercised in theextrapolation of small-animal-model biodistribution data to human scale.

Confined Compression of a Tissue-Equivalent: Collagen Fibril and Cell Alignment in Response to Anisotropic Strain

A method to impose and measure a one dimensional strain field via confined compression of a tissue-equivalent and measure the resulting cell and collagen fibril alignment was developed Strain was determined locally by the displacement of polystyrene beads dispersed and entrapped within the network of collagen fibrils along with the cells, and it was correlated to the spatial variation of collagen network birefringence and concentration. Alignment of fibroblasts and smooth muscle cells was determined based on the long axis of elongated cells. Cell and collagen network alignment were observed normal to the direction of compression after a step strain and increased monotonically up to 50% strain. These results were independent of time after straining over 24 hr despite continued cell motility after responding instantly to the step strain with a change in alignment by deforming/convecting with the strained network. Since the time course of cell alignment followed that of strain and not stress which, due to the viscoelastic fluid-like nature of the network relaxes completely within the observation period, these results imply cell alignment in a compacting tissue-equivalent is due to fibril alignment associated with anisotropic network strain. Estimation of a contact guidance sensitivity parameter indicates that both cell types align to a greater extent than the surrounding fibrils.

Modeling Passive Mechanical Interaction Between Aqueous Humor and Iris

Certain forms of glaucoma are associated with displacement of the iris from its normal contour. We present here a mathematical model of the coupled aqueous humor-iris system that accountsfor the contribution of aqueous humor flow and passive iris deformability to the iris contour. The aqueous humor is modeled as a Newtonian fluid, and the iris is modeled as a linear elastic solid. The resulting coupled equation set is solved by the finite element method with mesh motion in response to iris displacement accomplished by tracking a pseudo-solid overlying the aqueous humor. The model is used to predict the iris contour in healthy and diseased eyes. The results compare favorably with clinical observations, supporting the hypothesis that passive iris deformation can produce the iris contours observed using ultrasound biomicroscopy.

Coupled macroscopic and microscopic scale modeling of fibrillar tissues and tissue equivalents

Collagen mechanics are crucial to the function and dysfunction of many tissues, including blood vessels and articular cartilage, and bioartificial tissues. Previous attempts to develop computer simulations of collagenous tissue based on macroscopic property descriptions have often been limited in application by the simplicity of the model; simulations based on microscopic descriptions, in contrast, have numerical limitations imposed by the size of the mathematical problem. We present a method that combines the tractability of the macroscopic approach with the flexibility of the microstructural approach. The macroscopic domain is divided into finite elements (as in standard FEM). Each element contains a microscopic scale network. Instead of a stress constitutive equation; the macroscopic problem is distributed over the microscopic scale network and solved in each element to satisfy the weak formulation of Cauchys stress continuity equation over the macroscopic domain. The combined method scales by order 1.1 as the overall number of degrees of freedom is increased, allowing it to handle larger problems than a direct microstructural approach. Model predictions agree qualitatively with tensile tests on isotropic and aligned reconstituted type I collagen gels.

Intrinsic kinetics for rapid decomposition of methane in an aerosol flow reactor

Abstract A one-dimensional nonisothermal model is developed for the high-temperature rapid dissociation of methane in a fluid-wall graphite aerosol flow reactor. Intrinsic reaction kinetics are identified through simulation of the model and comparison to experimental results. The dissociation rate can be described by d X d t =6×10 11 exp −25000 T (1−X) 4.4 s −1 over the temperature range 1533 K and residence time range 0.9 s . This rate expression is useful for describing high-temperature short residence time processes for producing hydrogen and carbon black by methane decomposition (CH4→C+2H2).

MECHANICAL CHARACTERIZATION OF THE BOVINE IRIS

Quantification of the mechanical properties of the iris is necessary to assess the clinical significance of passive iris deformation, which has been suggested as a mechanism for certain forms of glaucoma. Extension tests were performed on isolated bovine irises to determine the passive mechanical behavior of the iris and the contribution of each of its two constituent muscles, the sphincter iridis and the dilator pupillae, to the overall properties. Because of the shape of the iris and our desire to use intact tissue, a loop experiment was performed in which the iris was stretched by hooking the sample and pulling. A simple mathematical model was used to account for the geometry of the experiment and the progressive recruitment of tissue. Radial extension experiments on samples dissected from the iris were also performed. The iris was found to be anisotropic, elastic, and incompressible. The average azimuthal Youngs modulus of the sphincter was found to be 340 kPa; the average azimuthal Youngs modulus of the dilator was found to be 890 kPa, which was significantly higher (p < 0.01). The radial Youngs modulus of the dilator was found to be 9.6 kPa, much lower than the azimuthal value.

Adaptive Finite Element Analysis of the Anisotropic Biphasic Theory of Tissue-Equivalent Mechanics.

Abstract The nonlinear partial differential equations of the anisotropic biphasic theory of tissue-equivalent mechanics are solved with axial symmetry by an adaptive finite element system. The adaptive procedure operates within a method-of-lines framework using finite elements in space and backward difference software in time. Spatial meshes are automatically refined, coarsened, and relocated in response to error indications and material deformation. Problems with arbitrarily complex two-dimensional regions may be addressed. With meshes graded in high-error regions, the adaptive solutions have fewer degrees of freedom than solutions with comparable accuracy obtained on fixed quasi-uniform meshes. The adaptive software is used to address problems involving an isometric cell traction assay, where a cylindrical tissue equivalent is adhered at its end to fixed circular platens; a prototypical bioartificial artery; and a novel configuration that is intended as an initial step in a study to determine bioartificial arteries having optimal collagen and cell concentrations.

A Continuum Model for the Role of Fibroblast Contact Guidance in Wound Contraction

Wound repair is a basic and vital process for homeostasis. It is also complex: in full-thickness cutaneous wounds, where loss of dermis has occurred, there are characteristic phases of immediate inflammation, short-term granulation tissue formation (angiogenesis, the ingrowth of blood vessels, and fibroplasia, the infiltration of fibroblastic cells), and long-term wound matrix remodeling. Wound contraction, wherein the wound edge and surrounding skin move inward toward the wound center, occurs during fibroplasia. Fibroblastic cells secrete collagen and other extracellular matrix (ECM) components needed to transform the weak fibrin clot into a collagenous scar with mechanical strength. They are also responsible for the forces underlying wound contraction. The reader is referred to the books edited by Clark & Henson (1988) and Cohen et al. (1992) for an overview of the biology of wound repair.