Articular cartilage represents a primary target for tissue engineering strategies as it does not functionally regenerate within the joint. Many tissue engineering approaches have focused on the in vitro generation of neo-cartilage using chondrocyte-seeded scaffolds. Several studies have reported the morphological appearance of native cartilage, although its functional competence has not been demonstrated. Accordingly, mechanical conditioning has often been introduced to enhance biosynthetic activity of chondrocytes within 3D constructs. However although this strategy has significantly up-regulated proteoglycan synthesis, its effects on the synthesis of the other major solid constituent, type II collagen, has been modest. Analyses of normal joint activities reveal that cartilage is subjected to shear superimposed on uniaxial compression. This complex mechanical state has motivated the design of a biaxial loading system intended for use in vitro to stimulated bovine chondrocytes seeded in agarose constructs. This necessitated the redesign of the construct from cylindrical morphology to accommodate shear loading. The experimental approach was complemented with the development of computational models, which permitted prediction of both cell distortion under biaxial loading regimens and nutrient diffusion within the 3D constructs. An initial study established the profile of proteoglycan and collagen synthesis in free swelling cultures up to day 12. The introduction of dynamic compression (15% strain, 1 Hz for 48 h) enhanced proteoglycan synthesis significantly. In addition, when dynamic shear (10%, 1 Hz) was superimposed on dynamic compression, total collagen synthesis was also up-regulated, within 3 days of culture, without compromising proteoglycan synthesis. Histological analysis revealed marked collagen deposition around individual chondrocytes. However, a significant proportion (50%) of collagen was released into the culture medium, suggesting that it was not fully processed. The overall biosynthetic activity was enhanced more when the biaxial stimulation was applied in a continuous mode as opposed to intermittent loading. The present work offers the potential for a more effective preconditioning of cell-seeded constructs with functional integrity intended for use to resolve defects in joint cartilage.

Articular cartilage injuries occur frequently in the knee joint. Several methods have been implemented clinically, to treat osteochondral defects but none have been able to produce a long term, durable solution. Photopolymerizable cartilage tissue engineering approaches appear promising; however, fundamentally, forming a stable interface between the tissue engineered cartilage and native tissue, mainly subchondral bone and native cartilage, remains a major challenge. The overall objective of this research is to find a solution for the current problem of dislodgment of tissue engineered cartilage at the defect site for the treatment of degraded cartilage that has been caused due to knee injuries or because of mild to moderate level of osteoarthritis. For this, an in-vitro model was created to analyze the integration of tissue engineered cartilage with the bone, healthy and diseased cartilage over time. We investigated the utility of hydroxyapatite (HA) nanoparticles to promote controlled bone-growth across the bone-cartilage interface in an in vitro engineered tissue model system using bone marrow derived stem cells. We also investigated the application of HA nanoparticles to promote enhance integration between tissue engineered cartilage and native cartilage both in healthy and diseased states. Samples incorporated with HA demonstrated significantly higher interfacial shear strength (at the junction between engineered cartilage and engineered bone and also with diseased cartilage) compared to the constructs without HA (p < 0.05), after 28 days of culture. These findings indicate that the incorporation of HA nanoparticles permits more stable anchorage of the injectable hydrogel-based engineered cartilage construct via augmented integration between bone and cartilage.

Articular cartilage injuries occur frequently in the knee joint. Several methods have been implemented clinically, to treat osteochondral defects but none have been able to produce a long term, durable solution. Photopolymerizable cartilage tissue engineering approaches appear promising; however, fundamentally, forming a stable interface between the tissue engineered cartilage and native tissue, mainly subchondral bone and native cartilage, remains a major challenge. The overall objective of this research is to find a solution for the current problem of dislodgment of tissue engineered cartilage at the defect site for the treatment of degraded cartilage that has been caused due to knee injuries or because of mild to moderate level of osteoarthritis. For this, an in-vitro model was created to analyze the integration of tissue engineered cartilage with the bone, healthy and diseased cartilage over time. We investigated the utility of hydroxyapatite (HA) nanoparticles to promote controlled bone-growth across the bone-cartilage interface in an in vitro engineered tissue model system using bone marrow derived stem cells. We also investigated the application of HA nanoparticles to promote enhance integration between tissue engineered cartilage and native cartilage both in healthy and diseased states. Samples incorporated with HA demonstrated significantly higher interfacial shear strength (at the junction between engineered cartilage and engineered bone and also with diseased cartilage) compared to the constructs without HA (p < 0.05), after 28 days of culture. These findings indicate that the incorporation of HA nanoparticles permits more stable anchorage of the injectable hydrogel-based engineered cartilage construct via augmented integration between bone and cartilage.

No description available.