Broadly speaking, my research group is concerned with understanding the mechanics of biological growth and remodeling in connective soft tissue. This entails developing model systems and methods to study these phenomena under precise mechanochemical loading, using tools such as fibroblast-populated collagen gels and confocal microscopy. In parallel, we have developed corresponding computational models that possess significant enhancements over classical mechanical theories to allow for the coupling of growth, remodeling and mechanics. The combination of these experimental and theoretical approaches enables the formulation and testing of novel hypotheses of mechanobiology in order to engineer better tissue-equivalents and understand the basis for pathological states.
More specifically, my personal research interests and experience include
- Continuum and computational soft tissue mechanics
- Constitutive modeling of soft tissue remodeling
- Mechanical characterization of native and engineered soft tissue
- Image analysis methods for quantification of texture orientation and anisotropy in 3-D volumetric data
Research Projects
Here are snippets of my current ongoing research projects, with links to relevant technical reports and publications if available.
Continuum thermodynamics of internal variable-based constitutive models of biological remodeling
Among the many developmental processes in engineered and embryonic connective soft tissue, remodeling processes rely little on changes in collagen mass. Instead, an evolution of collagen microstructure occurs to enhance the mechanical properties of the tissue: fibroblast traction reorients collagen fibrils to produce structural anisotropy, while post-depositional fibril fusion serves to stiffen and strengthen the tissue. Current continuum treatments of remodeling have generally not considered the thermodynamic implications of model irreversibilities in terms of dissipation. It was shown previously that the dissipation associated with a common class of fibril reorientation evolution equations necessitates an internal variable formulation that is more than purely mechanical. Having also demonstrated that the combined effect leads to greater dissipation provided with a strain energy function convex in the fibril orientation vector, the objective of this work is to examine the relative dissipation characteristics between collagen fibril fusion and reorientation. To this end, an internal variable-based constitutive model with evolution equations for fibril reorientation and fusion is formulated and implemented in a finite element context. Considering engineered tendon as a model system, the dissipation associated with these remodeling processes are evaluated from the solutions to boundary-value problems modeling typical engineered tissue experiments. The dissipative characteristics of tissue constructs in these models suggest a thermodynamic stability conferred by cell-mediated remodeling that has not yet been explored.
Figure 1: *Unstretched cylindrical tendon model exhibiting random fiber orientations.
Figure 2: *Tendon model with fibers aligned in the direction of maximum stretch following remodeling under uniaxial extension.
Intensity gradient-based analysis of texture orientation distribution in volumetric image data
Development of tissue-specific mechanical anisotropy is crucial to effective and efficient function of connective soft tissue. This is especially important in the contexts of tissue engineering and wound repair in which it has been a major challenge to induce and/or guide the development of proper anisotropy. Any experimental and theoretical investigation of soft tissue mechanics thus benefits from quantification of the microstructual anisotropy from which the macroscopic function emerges. This requires both an appropriate microscopy or spectroscopy method and, frequently, image analysis techniques to process and apply the data. Here, the three-dimensional adaptation and extension of existing algorithms for assessing global texture orientation and anisotropy via gradients of image intensity is described. While it is hoped that the development is sufficiently general for a range of similar tissue morphologies and imaging modalities, the current thrust is toward quantifying the evolution of anisotropy in fibroblast-populated collagen gels using confocal laser scanning microscopy. To this end, a two-dimensional validation of the proposed method's performance as compared to conventional methods is demonstrated using realistic calibration test images, and a preliminary application to three-dimensional image volumes of an isotropic and an aligned collagen gel is presented.
Figure 3: *Confocal micrograph of isotropic collagen gel.
Figure 4: *Confocal micrograph of aligned collagen gel following compaction by entrapped fibroblasts.
Previous Research