Glycosaminoglycans (GAGs) are ubiquitous components in the cartilage extracellular matrix (ECM). Ultrastructural arrangement of ECM and GAG-mediated interactions with collagen are known to govern the mechanics in articular cartilage, but these interactions are less clear in other cartilage types. Therefore, this article reviews the current literature on ultrastructure of articular, auricular, meniscal, and nasal septal cartilage, seeking insight into GAG-mediated interactions influencing mechanics. Ultrastructural features of these cartilages are discussed to highlight differences between them. GAG-mediated interactions are reviewed under two categories: interactions with chondrocytes and interactions with other fibrillar macromolecules of the ECM. Moreover, efforts to replicate GAG-mediated interactions to improve mechanical integrity of tissue-engineered cartilage constructs are discussed. In conclusion, studies exploring cartilage specific GAGs are poorly represented in the literature, and the ultrastructure of nasal septal and auricular cartilage is less studied compared with articular and meniscal cartilages. Understanding the contribution of GAGs in cartilage mechanics at the ultrastructural level and translating that knowledge to engineered cartilage will facilitate improvement of cartilage tissue engineering approaches.

Objective: To investigate GAG-ECM (glycosaminoglycan–extracellular matrix) interactions in different cartilage types. To achieve this, we first aimed to determine protocols for consistent calculation of GAG content between cartilage types. Design: Auricular cartilage containing both collagen and elastin was used to determine the effect of lyophilization on GAG depletion activity. Bovine articular, auricular, meniscal, and nasal cartilage plugs were treated using different reagents to selectively remove GAGs. Sulfated glycosaminoglycan (sGAG) remaining in the sample after treatment were measured, and sGAG loss was compared between cartilage types. Results: The results indicate that dry weight of cartilage should be measured prior to cartilage treatment in order to provide a more accurate reference for normalization. Articular, meniscal, and nasal cartilage lost significant amounts of sGAG for all reagents used. However, only hyaluronidase was able to remove significant amount of sGAG from auricular cartilage. Furthermore, hyaluronidase was able to remove over 99% of sGAG from all cartilage types except auricular cartilage where it only removed around 76% of sGAG. The results indicate GAG-specific ECM binding for different cartilage types and locations. Conclusions: In conclusion, lyophilization can be performed to determine native dry weight for normalization without affecting the degree of GAG treatment. To our knowledge, this is the first study to compare GAG-ECM interactions of different cartilage types using different GAG extraction methods. Degree of GAG depletion not only varied with cartilage type but also the same type from different anatomic locations. This suggests specific structure-function roles for GAG populations found in the tissues.