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Microstructural heterogeneity directs micromechanics and mechanobiology in native and engineered fibrocartilage.

Nature materials (2016-01-05)
Woojin M Han, Su-Jin Heo, Tristan P Driscoll, John F Delucca, Claire M McLeod, Lachlan J Smith, Randall L Duncan, Robert L Mauck, Dawn M Elliott
RESUMEN

Treatment strategies to address pathologies of fibrocartilaginous tissue are in part limited by an incomplete understanding of structure-function relationships in these load-bearing tissues. There is therefore a pressing need to develop micro-engineered tissue platforms that can recreate the highly inhomogeneous tissue microstructures that are known to influence mechanotransductive processes in normal and diseased tissue. Here, we report the quantification of proteoglycan-rich microdomains in developing, ageing and diseased fibrocartilaginous tissues, and the impact of these microdomains on endogenous cell responses to physiologic deformation within a native-tissue context. We also developed a method to generate heterogeneous tissue-engineered constructs (hetTECs) with non-fibrous proteoglycan-rich microdomains engineered into the fibrous structure, and show that these hetTECs match the microstructural, micromechanical and mechanobiological benchmarks of native tissue. Our tissue-engineered platform should facilitate the study of the mechanobiology of developing, homeostatic, degenerating and regenerating fibrous tissues.

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Anti-Collagen Type I Antibody, clone 5D8-G9, clone 5D8-G9, Chemicon®, from mouse