Human nasal cartilage: Functional properties and structure-function relationships for the development of tissue engineering design criteria.

Nose reconstruction often requires scarce cartilage grafts. Nasal cartilage properties must be determined to serve as design criteria for engineering grafts. Thus, mechanical and biochemical properties were obtained in multiple locations of human nasal septum, upper lateral cartilage (ULC), and lower lateral cartilage (LLC). Within each region, no statistical differences among locations were detected, but anisotropy at some septum locations was noted. In the LLC, the tensile modulus and ultimate tensile strength (UTS) in the inferior-superior direction were statistically greater than in the anterior-posterior direction. Cartilage from all regions exhibited hyperelasticity in tension, but regions varied in degree of hyalinicity (i.e., Col II:Col I ratio). The septum contained the most collagen II and least collagen I and III, making it more hyaline than the ULC and LLC. The septum had a greater aggregate modulus, UTS, and lower total collagen/wet weight (Col/WW) than the ULC and LLC. The ULC had greater tensile modulus, DNA/WW, and lower glycosaminoglycan/WW than the septum and LLC. The ULC had a greater pyridinoline/Col than the septum. Histological staining suggested the presence of chondrons in all regions. In the ULC and LLC, tensile modulus correlated with total collagen content, while aggregate modulus correlated with pyridinoline content and weakly with pentosidine content. However, future studies should be performed to validate these proposed structure-function relationships. This study of human nasal cartilage provides 1) crucial design criteria for nasal cartilage tissue engineering efforts, 2) quantification of major and minor collagen subtypes and crosslinks, and 3) structure-function relationships. Surprisingly, the large mechanical properties found, particularly in the septum, suggests that nasal cartilage may experience higher-than-expected mechanical loads. STATEMENT OF SIGNIFICANCE: While tissue engineering holds promise to generate much-needed cartilage grafts for nasal reconstruction, little is known about nasal cartilage from an engineering perspective. In this study, the mechanical and biochemical properties of the septum, upper lateral cartilage (ULC), and lower lateral cartilage (LLC) were evaluated using cartilage-specific methods. For the first time in this tissue, all major and minor collagens and collagen crosslinks were measured, demonstrating that the septum was more hyaline than the ULC and LLC. Additionally, new structure-function relationships in the ULC and LLC were identified. This study greatly expands upon the quantitative understanding of human nasal cartilage and provides crucial engineering design criteria for much-needed nasal cartilage tissue engineering efforts.

Toward tissue-engineering of nasal cartilages.

Nasal cartilage pathologies are common; for example, up to 80% of people are afflicted by deviated nasal septum conditions. Because cartilage provides the supportive framework of the nose, afflicted patients suffer low quality of life. To correct pathologies, graft cartilage is often required. Grafts are currently sourced from the patient's septum, ear, or rib. However, their use yields donor site morbidity and is limited by tissue quantity and quality. Additionally, rhinoplasty revision rates exceed 15%, exacerbating the shortage of graft cartilage. Alternative grafts, such as irradiated allogeneic rib cartilage, are associated with complications. Tissue-engineered neocartilage holds promise to address the limitations of current grafts. The engineering design process may be used to create suitable graft tissues. This process begins by identifying the surgeon's needs. Second, nasal cartilages' properties must be understood to define engineering design criteria. Limited investigations have examined nasal cartilage properties; numerous additional studies need to be performed to examine topographical variations, for example. Third, tissue-engineering processes must be applied to achieve the engineering design criteria. Within the recent past, strategies have frequently utilized human septal chondrocytes. As autologous and allogeneic rib graft cartilage is used, its suitability as a cell source should also be examined. Fourth, quantitative verification of engineered neocartilage is critical to check for successful achievement of the engineering design criteria. Finally, following the FDA paradigm, engineered neocartilage must be orthotopically validated in animals. Together, these steps delineate a path to engineer functional nasal neocartilages that may, ultimately, be used to treat human patients. STATEMENT OF SIGNIFICANCE: Nasal cartilage pathologies are common and lead to greatly diminished quality of life. The ability to correct pathologies is limited by cartilage graft quality and quantity, as well as donor site morbidity and surgical complications, such as infection and resorption. Despite the significance of nasal cartilage pathologies and high rhinoplasty revision rates (15%), little characterization and tissue-engineering work has been performed compared to other cartilages, such as articular cartilage. Furthermore, most work is published in clinical journals, with little in biomedical engineering. Therefore, this review discusses what nasal cartilage properties are known, summarizes the current state of nasal cartilage tissue-engineering, and makes recommendations via the engineering design process toward engineering functional nasal neocartilage to address current limitations.