Soft Tissue Mechanobiology

Mechanical forces govern the structure and biology of nearly all soft connective tissues. We are interested in understanding how cells sense mechanical forces through the extracellular matrix, and how increased or decreased forces disrupt homeostasis and lead to extracellular matrix adaptation or degeneration. To this end, we use novel in vitro tendon models combined with custom-built controllable mechanical bioreactors to understand how external mechanical forces influence tissue biology, specifically extracellular matrix remodeling, tissue inflammation, and apoptosis. In addition, we use sophisticated mechanical testing methods at multiple hierarchical scales to measure the dynamic mechanical function of many soft connective tissues. This includes whole tissue mechanical properties, measurements of tissue viscoelasticity and poroelasticity/fluid flow, and nano- and micro-mechanics. Current projects include investigating how different loading directions and intensities influence tendon biology, as well as studying permeability and solute transport properties using nanoscale rheology in various soft tissues.

Tendon and Ligament Aging

A major player in the etiology and/or progression of tendon degeneration is tissue aging. The effects of aging on changes in tendon ECM and mechanical function have been long debated, but it is established that tenocytes do exhibit signs of biological aging. In the past decades, researchers have identified many changes in cell processes that are associated with natural aging. Using aged mouse models combined with novel explant and cell culture studies, our goal is to identify how altered cell processes influence mechanosensing and ECM remodeling, potentially leading to injury. We have already found significant alterations in the inflammatory processes, metabolic activity and sensitivity to mechanical forces in explants from aged mice and are currently exploring age-related differences in inflammation-induced injuries.

In Vitro ​Models of Injury

We have been working to develop in vitro models of tissue homeostasis to understand normal processes of ECM remodeling, as well as in vitro injury models. Specifically, we developed a clinically-relevant whole tendon explant model, as well as a rotator cuff organ culture injury model. Unlike single-cell analyses or tissue-engineered approaches, these models allow us to explore the biological response to altered mechanical loading in a controllable environment while preserving native structure, cell-cell junctions, and interaction with adjacent tissues. Furthermore, this platform allows us to identify key molecular pathways that can be explored through additional cell culture experiments and can be used as a testbed for potential therapeutics that can be evaluated using in vivo approaches. In our bone-tendon-muscle injury model, we have been recently investigating the roles of inflammation and tissue crosstalk in tendon degeneration.

Sex Differences and Hormonal Influence in ECM Remodeling

Much of the animal and human research studying tendon and ligament injuries has been performed only in male specimens. However, several groups have recently been investigating sex differences in tendon biology, finding significant alterations that will impact clinical treatment of tendon disease. We have also been interested in sex differences, specifically as they relate to aging, and have found a number of differences in the inflammatory profile of young specimens following injury, as well as differences in the regulation of senescence pathways in aging. Current projects include investigation into the ECM remodeling processes in male versus female tendons following alterations to macroscale mechanical loading.