“Our first question when we saw these microdomains was, ‘Are they normal, or are they associated with pathology?'” Dawn Elliott, PhD, professor and chair of Delaware’s department of Biomedical Engineering said in a statement.

The researchers performed studies on cow and donated human tissue and found that microdomains were present in very young, healthy tissue, but that they grew larger with age, injury, and disorders such as osteoarthritis. This suggests that the increased size of microdomains is related to disease onset and tissue function loss.

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The study’s authors surmised that the fibrous regions and proteoglycan-rich microdomains were not receiving the same mechanical signals; cells within the microdomains did not respond to mechanical inputs, while cells in the fibrous regions switched calcium signals on and off in response to physical activity.

The researchers then developed a micro-scaled culture platform to generate engineered tissue with both normal and abnormal features, observing differences in physical structure and cell signaling in response to mechanical loading.

This engineered tissue replicates key features of degenerating tissue and can serve as a platform from which to test new physical therapy treatments or drug-based treatment strategies.

“This engineered disease model will enable the development of new treatments for degenerative disease in numerous types of connective tissues,” Dr Mauck said in a statement.


Han WM, Heo S, Driscoll TP, et al. Microstructural heterogeneity directs micromechanics and mechanobiology in native and engineered fibrocartilage. Nat Mater. 2016; doi:10.1038/nmat4520.