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DIAGNOSTICS

Diagnosis of some diseases often requires specialized expertise and costly processes. Mechanical changes have been seen to correlate with several diseases and may provide a chance to make early diagnoses based on the mechanical fingerprint of cells and tissues. In particular, mechanical signatures play a role in diagnosis of osteoarthritis, fibrosis, and cancer.

Osteoarthritis diagnosis

Cartilage plays an important role in the overall biomechanical system, so it is not surprising that the mechanical behavior of cartilage can be used to diagnosis disorders with its function, such as osteoarthritis. Osteoarthritis results in significant changes, including deterioration of the articular cartilage and formation of new bone at the articular surface. Several measurements of the mechanical properties of cartilage correlate with osteoarthritis, including tensile, compressive, and shear moduli, as well as swelling of the tissue [1]. Furthermore, the dynamic moduli of early-stage cartilage samples have been shown to be an indicator of osteoarthritis, and can be measured with multiple techniques, including nanoindentation [2]. Some research has also led to the potential for in-vivo mechanical characterization of osteoarthritis using high frequency ultrasound to characterize mechanical properties [3].

Cancer diagnosis

Cancer has been shown to have a mechanical footprint, both from the stiffness of the tumors and the extracellular matrix near the tumor. Furthermore, stiffness has been shown to be an indicator of resistance to therapy, both from the stiffness of the tumor and extracellulcar matrix [4]. The mechanical compliance of cancer cells has been shown to be significantly different from non-cancer cells, as shown by using a microfluidic optical stretcher [5]. Several aspects of the extracellular matrix can indicate cancer and be used to understand how it will progress [6]. In particular, pancreatic cancer progression has been characterized by AFM measurements of the extracellular matrix [7] (figure).

Fibrosis diagnosis

Fibrosis is well known to be correlated with tissue stiffening, and research has shown that the mechanism of fibrosis is complex and requires defined mechanical environments in order to properly model the disease [8, figure]. Some hydrogels have even been developed to change stiffness over time in order to better mimic the ECM changes during fibrosis to build better disease models [8]. Another study has indented fibrin gels with microvessels to measure the changes in stiffness with a variety of treatments to estimate the ECM degradation [9]. AFM mapping of tissue elasticity has shown new insights onto the mechanisms driving fibrosis by analyzing the stiffness profile of fibrotic tissue and comparing with histological staining [10]. In addition to diagnosis, disease models and understanding of fibrosis have been better understood by used nanoindentation to characterize fibrotic regions of tissues. These measurements have led to an understanding of a feedback mechanism that amplifies fibrosis [11].   

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