Featured Research Publications
Hyperelastic characterization reveals proteoglycans drive the nanoscale strain-stiffening response in hyaline cartilage
Journal of Biomechanics, Volume 146, January 2023, 111397
Degenerative diseases such as osteoarthritis (OA) result in deterioration of cartilage extracellular matrix (ECM) components, significantly compromising tissue function. For measurement of mechanical properties at micron resolution, atomic force microscopy (AFM) is a leading technique in biomaterials research, including in the study of OA. It is common practice to determine material properties by applying classical Hertzian contact theory to AFM data. However, errors are consequential because the application of a linear elastic contact model to tissue ignores the fact that soft materials exhibit nonlinear properties even at small strains, influencing the biological conclusions of clinically-relevant studies. Additionally, nonlinear material properties are not well characterized, limiting physiological relevance of Young’s modulus. Here, we probe the ECM of hyaline cartilage with AFM and explore the application of Hertzian theory in comparison to five hyperelastic models: NeoHookean, Mooney-Rivlin, Arruda-Boyce, Fung, and Ogden.
Nuclear Stiffness Decreases with Disruption of the Extracellular Matrix in Living Tissues
Small, Vol. 7, Issue 6, February 2021
Reciprocal interactions between the cell nucleus and the extracellular matrix lead to macroscale tissue phenotype changes. However, little is known about how the extracellular matrix environment affects gene expression and cellular phenotype in the native tissue environment. Here, it is hypothesized that enzymatic disruption of the tissue matrix results in a softer tissue, affecting the stiffness of embedded cell and nuclear structures. The aim is to directly measure nuclear mechanics without perturbing the native tissue structure to better understand nuclear interplay with the cell and tissue microenvironments.
Particulate ECM biomaterial ink is 3D printed and naturally crosslinked to form structurally-layered and lubricated cartilage tissue mimics
BioFabrication, Vol. 14 No. 2, 2022
Articular cartilage is a layered tissue with a complex, heterogeneous structure and lubricated surface which is challenging to reproduce using traditional tissue engineering methods. Three-dimensional printing techniques have enabled engineering of complex scaffolds for cartilage regeneration, but constructs fail to replicate the unique zonal layers, and limited cytocompatible crosslinkers exist. To address the need for mechanically robust, layered scaffolds, we developed an extracellular matrix particle-based biomaterial ink (pECM biomaterial ink) which can be extruded, polymerizes via disulfide bonding, and restores layered tissue structure and surface lubrication.
The Role of Mechanobiology in Cancer Metastasis
Mechanobiology: From Molecular Sensing to Disease, Chapter 1.4, 2020
The skeleton is the preferred site of metastasis for multiple cancers (e.g., breast, prostate), yet it remains incurable. The mechanical environment of whole bones, including the mineralized tissue and bone marrow, is a rich source of cues that directs resident bone cells, and thus also likely modulates disseminated metastatic tumor cells that have localized to the marrow compartment. Here, we provide an overview of the relevant mechanical cues in bone marrow microenvironment and discuss what is currently known of their impacts on tumor progression. We also discuss possible mechanosensing mechanisms that tumor cells may utilize in the bone marrow.