Minipig costal and knee cartilage structure-function relationships and their use as cell sources for tissue-engineered analogous cellular products for cartilage repair

Toward the development of biologic products intended to repair articular cartilage, this study evaluated native structure-function relationships of rib and knee cartilage and compared the capacity of articular chondrocytes (ACs) and costochondral cells (CCs) to generate tissue-engineered analogous cellular products (ACPs) for preclinical cartilage repair studies. Utilizing the relevant preclinical model of the Yucatan minipig, both knee and rib cartilages were characterized by topography and age. Key findings include that: 1) knee cartilage had higher tensile properties than rib cartilage (e.g., ultimate tensile strength of adult knee cartilage being 218 % of adult rib cartilage), 2) rib cartilage had higher compressive properties than knee cartilage (e.g., aggregate modulus of adult rib cartilage being 177 % of adult knee cartilage), 3) functional (i.e., biomechanical and biochemical) properties were dependent on age (e.g., adult coefficient of friction being 186 % of that of the juvenile in the medial-lateral axis of the knee), 4) functional properties were dependent on topography, 5) compressive properties were significantly correlated to glycosaminoglycan content and hydration, and 6) tensile properties were significantly correlated to collagen content. Additionally, juvenile ACs and CCs were compared for their capacity to generate self-assembled neocartilage with constructs achieving functionality index values (i.e., a weighted average of neocartilage functional properties compared to native tissue) of 0.54 and 0.44, respectively, when compared to native adult minipig knee cartilage. Overall, this study provides gold-standard characterization values for minipigs of different ages for preclinical cartilage repair studies and demonstrates that both ACs and CCs can be used to generate functional self-assembled neocartilage ACPs. STATEMENT OF SIGNIFICANCE: Toward the clinical translation of tissue-engineered cartilage implants, this study characterizes the functional properties of knee and rib cartilage in the clinically relevant Yucatan minipig model. Additionally, it evaluates the ability of knee- and rib-derived chondrocytes to generate neocartilage that recapitulates the functional properties of native cartilage tissues. Age-related changes in rib and knee cartilage are also described, along with structure-function relationships involving correlating biochemical composition and mechanical properties of cartilage tissues. Overall, this study provides data essential to the translation of cartilage implants for the knee and describes how these data are relevant to the FDA regulatory process.