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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.

Tissue-engineering (TE) efforts for ear reconstruction often fail due to mechanical incompetency. It is therefore key for successful auricular cartilage (AUC) TE to ensure functional competency, that is, to mimic the mechanical properties of the native ear tissue. A review of past attempts to engineer AUC shows unsatisfactory functional outcomes with various cell-seeded biodegradable polymeric scaffolds in immunocompetent animal models. However, promising improvements to construct stability were reported with either mechanically reinforced scaffolds or novel two-stage implantation techniques. Nonetheless, quantitative mechanical evaluation of the constructs is usually overlooked, and such an evaluation of TE constructs alongside a benchmark of native AUC would allow real-time monitoring and improve functional outcomes of auricular TE strategies. Although quantitative mechanical evaluation techniques are readily available for cartilage, these techniques are designed to characterize the main functional components of hyaline and fibrous cartilage such as the collagen matrix or the glycosaminoglycan network, but they overlook the functional role of elastin, which is a major constituent of AUC. Hence, for monitoring AUC TE, novel evaluation techniques need to be designed. These should include a characterization of the specific composition and architecture of AUC, as well as mechanical evaluation of all functional components. Therefore, this article reviews the existing literature on AUC TE as well as cartilage mechanical evaluation and proposes recommendations for designing a mechanical evaluation protocol specific for AUC, and establishing a benchmark for native AUC to be used for quantitative evaluation of TE AUC.