UC San Diego

Adult articular cartilage can function normally over decades as the load bearing, low-friction, and wear-resistant tissue in synovial joints. The primary structural macromolecules of cartilage, collagen, and proteoglycan, contribute to mechanical function and vary during antenatal growth in animal models. Collagen and proteoglycan content and assembly also affect cartilage swelling pressure and growth in vitro. However, the extent and time-course of variation in mechanical function and biochemical content during normal human development is unclear. In addition, the way in which cartilage attains its adult form, covering an increasing joint surface area until adulthood, is not well understood. Thus, the objectives of this thesis were to (1) describe orthobiologic approaches to cartilage repair, determine maturation-related variation in (2) compressive and (3) tensile mechanical functions, and (4) biochemical content during normal human postnatal development, and delineate how (5) depth-varying tissue growth leads to formation of mature collagen network architecture, and how (6) regulatory cytokines and growth factors, as well as alterations in tissue content, affect in vitro cartilage growth. The load-bearing compressive and tensile properties of articular cartilage improved between infants, children, and adults. In particular, the equilibrium confined compression modulus increased 3-fold between children and adults, and tensile modulus and strength peaked in children. Enhanced mechanical function was positively correlated with increased collagen and glycosaminoglycan. In a kinematic model of collagen reorientation, using the mouse medial femoral condyle as a model organ, depth-varying axial and lateral deformations in vivo, wherein the axial stretch increases exponentially, and the lateral stretch decreases linearly, with depth from the surface yields mature-like collagen orientations. In vitro cartilage explant growth was regulated and was altered by the assembly of collagen and content of proteoglycan. Immature cartilage explant growth was primarily axial, with both axial and lateral growth strains highest near the articular surface. Axial and shear growth strains were enhanced in the superficial and deep cartilage by mitigation of collagen crosslink formation and diminished by removal of proteoglycans. The above studies establish benchmarks for postnatal maturation of normal human femoral condyle. The time course of variation in cartilage compressive and tensile properties during maturation is distinctive between humans and bovines and implicates differences in loading demands, as well as onset of puberty as mechanisms of cartilage maturation. Depth-varying growth mechanisms during maturation may allow for concurrent expansion of the tissue near the articular surface and maturation of the deeper regions. Modulation of in vitro growth during assembly or design of engineered tissues may be a useful tool in recapitulating native-like structural properties.