15502-m-pleumeekers

DISCUSSION To our knowledge this is the first study that compares the biochemical, 3D structural and mechanical differences between all three facial cartilage types in human donors. By measuring differences in cartilage composition, structure, and stiffness on the ECM level we aimed to identify significant aspects of facial cartilage architecture necessary for adequate tissue engineering. This is relevant for tissue engineering of cartilage, which has received massive attention the last decade. A variety of different cell types and scaffolds have been proposed for auricular or nasal cartilage engineering. [52, 56, 58, 199-201] Although promising results have been obtained, most regenerated tissues generally are only a very marginal substitution of the original tissue. This study reveals that there are significant differences between cartilage types on the ECM scale, even if they are similar in mechanical properties. The composition of ear cartilage is known to be different compared to septal cartilage in that it contains elastic fibers. [201] We could measure small amounts of elastin in nasal cartilage with biochemical analyses. This is in line with a study in white New Zealand rabbit’s where, using immunohistochemical staining, high elastin content was found specifically in the ear cartilage matrix compared to only moderate elastin content in the nasal septal pericellular regions. [143] The fact that the matrix comprises for an substantial part of elastin suggests that this may offer an important attribution to the mechanical qualities of ear cartilage. [138] The effective Young’s modulus was significantly lower in auricular and ala nasi cartilage than in nasal septum cartilage. However, stiffness between ear and ala nasi cartilage was not statistically different, although there was a clear difference in elastin content. These findings match the observations of Griffin and colleagues who found similar differences in stiffness between ala nasi and septal cartilage. [28] In a recent paper Nimeskern and colleagues [202] explored how elastin influences the mechanical behaviour of cartilage. They found different viscoelastic behaviours of bovine hyaline articular cartilage and ear cartilage, with ear cartilage being more elastic whereas articular cartilage demonstrated a higher resistance to instantaneous loading. Upon enzymatic treatment to remove elastin and/or sGAG, they demonstrated that the compressive mechanical properties of ear cartilage appeared to be mainly due to the elastin fiber network whereas these properties were provided by collagen in articular cartilage. Moreover, the influence of sGAG on mechanical behaviour appeared different between the cartilage types: in ear cartilage sGAG had no major influence on mechanics whereas in articular cartilage sGAG had a clear influence. Although a different tissue, this apparent discrepancy between the expected role of elastin and the actual mechanical properties was also noted in dermal scar tissue. [203] This demonstrates the complex role of tissue composition in mechanical function of the tissue. The differences in mechanical behaviour between the cartilage types could be determined not only by their biochemical compositions but also by tissue architecture. Using Multiple-photon laser scanning microscopy, the 3D structure of the different cartilage types could be depicted in high detail. Interestingly, the ala nasi, although very similar in appearance 53 FACIAL CARTILAGE CHARACTERISTICS 3

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