Figure 1.

Hierarchical structure of articular cartilage extracellular matrix (ECM). (a) Schematic of the structure and major constituents of cartilage ECM: type II/IX/XI collagen fibril network and aggrecan–hyaluronan aggregates.¹⁸ Molecular density is reduced to increase clarity. Adapted with permission from ref 31. Copyright 2014 American Chemical Society. (b) Matrix molecular composition and organization in different extracellular regions. Adapted with permission from ref 10. Copyright 2009 Wiley. (c,d) Zonal heterogeneity: Toluidine blue histology images of rabbit cartilage showing (c) the pericellular, territorial, and interterritorial matrices; (d) depth-dependent zonal heterogeneity. Adapted with permission from ref 11. Copyright 2006 Osteoarthritis Research Society International. (e) Collagen fibril orientation distribution in relation to cartilage surface, measured by the quantitative polarized light microscopy (qPLM) on mature porcine cartilage. Adapted with permission from ref 13. Copyright 2006 Osteoarthritis Research Society International. (f) Nanostructure of collagen fibril network measured by helium ion microscopy on proteoglycan-removed rabbit cartilage. Adapted with permission from ref 14. Copyright 2012 Wiley. (g) Nanostructure of aggrecan-hyaluronan aggregates imaged by (top panel) transmission electron microscopy and (middle panel) tapping mode AFM, as well as (bottom panel) nanstructure of individual aggrecan by tapping mode AFM. Adapted with permission from refs 17 and 20. Copyright 2010 Osteoarthritis Research Society International and 1983 Gustav Fischer Verlag.