title: Microstructural heterogeneity directs micromechanics and mechanobiology in native and engineered fibrocartilage.
abstract: 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.
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Woojin M
authors.initials: WM
authors.lastname: Han
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.|Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Heo
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.|Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Tristan P
authors.initials: TP
authors.lastname: Driscoll
authors.affiliation: Department of Biomedical Engineering, University of Delaware, Newark, Delaware 19716, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Delucca
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.|Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Claire M
authors.initials: CM
authors.lastname: McLeod
authors.affiliation: Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.|Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Lachlan J
authors.initials: LJ
authors.lastname: Smith
authors.affiliation: Department of Biomedical Engineering, University of Delaware, Newark, Delaware 19716, USA.|Department of Biological Sciences, University of Delaware, Newark, Delaware 19716, USA.
authors.forename: Randall L
authors.initials: RL
authors.lastname: Duncan
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.|Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Mauck
authors.affiliation: Department of Biomedical Engineering, University of Delaware, Newark, Delaware 19716, USA.
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Elliott
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D020013:Calcium Signaling; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D005260:Female; D051445:Fibrocartilage / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008297:Male; D040542:Mechanotransduction, Cellular; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D008875:Middle Aged; D011509:Proteoglycans / Q000378:metabolism*; D013314:Stress, Mechanical; D023822:Tissue Engineering; D016474:Weight-Bearing
chemical_list: D011509:Proteoglycans