The engineering of functionally competent cartilage depends significantly on the biochemical and mechanical environment in which the tissue-engineered (TE) construct develops. Our long-term objective is to optimize the functional tissue engineering of cartilage as a step toward increasing the availability of regenerative and reparative treatments for patients with musculoskeletal disorders such as osteoarthritis. The specific hypothesis is that biomechanical properties of TE cartilage can be optimized if control of scaffold degradation and mechanical stimulation combined with online ultrasonic imaging and monitoring capabilities are integrated into a bioreactor design. We base this hypothesis on the observations that 1) copolymer gel scaffolds with bimodal degradation profiles improve distribution of extracellular matrix (ECM) molecules while maintaining mechanical properties of the initial hydrogel, 2) high-frequency ultrasound is sensitive to ECM content, and 3) mechanical stimulation of engineered cartilage leads to improved biosynthesis and functionality. Based on these observations, we take a multi-disciplinary science and engineering approach to improve the quality of TE cartilage. The specific aims are to: 1. Incorporate triggerable markers into a poly(ethylene glycol) based hydrogel with encapsulated chondrocytes in order to permit control of the degradation profile of the polymer scaffold as the tissue-engineered cartilage evolves. We will characterize the degradation profiles of these hydrogels in response to an exogenously delivered lipase enzyme, and we will quantify ECM production and distribution when chondrocytes are encapsulated in these hydrogels. 2. Measure and model the mechanical and ultrasonic properties of TE cartilage and bovine articular cartilage to enable online monitoring of the quality of TE cartilage. We will establish target properties for TE cartilage based on acoustic microscopy measurements of immature bovine cartilage. A quality index for ECM production in TE cartilage will be based on a combination of multiple ultrasonic and mechanical parameters determined from experimental measurements and numerical models. 3. Design a bioreactor for tissue engineering of cartilage with feedback control capabilities to optimize quality of the TE cartilage. We will integrate quantitative ultrasonic imaging and measurement capabilities into the bioreactor to monitor the quality of the developing TE cartilage. We will incorporate feedback control using a heuristic control loop to modify the biochemical and mechanical environment in order to optimize ECM production.

R01AR053126

2005-09-25

2011-07-31