EAPSI: Microscale Gradient Generation Device for Creating the Cellular Types Observed Across the Bone-Cartilage Interface

Boys Alexander, Schwenksville PA

Investigators

Abstract

Articular cartilage is soft tissue that covers the ends of long bones in human joints, such as the knee joint, and acts to mitigate stress and wear. Articular cartilage transitions into bone through the osteochondral interface. The breakdown of articular cartilage and the osteochondral interface results in osteoarthritis, a disease affecting approximately 27 million Americans according to the CDC. Articular cartilage shows poor healing properties due to its lack of blood flow. Tissue engineered implants offer a promising method for healing articular cartilage in that they can be customized to fit the specific shapes and sizes of defects in articular cartilage, but these implants must show similar structure to cartilage found in the body. The structure and composition of articular cartilage changes with depth and proximity to bone, and these changes are consistent with changes in chondrocyte phenotype (the general shape and size of cartilage cells). This study is directed at recreating these cellular changes by placing chondrocytes into a collagen gel to simulate the knee environment and then applying a gradient of chemical factors that cause the cells to act as they would at the osteochondral interface. This work is performed in collaboration with Dr. Xingyu Jiang of the Chinese National Center for NanoScience and Technology (NCNST), an expert in using small fluid-based devices to affect cellular phenotype. The study will create a flow-less chemical concentration gradient that allows for intercell signaling in a collagen gel environment that is similar to the extracellular matrix of articular cartilage. This gradient will be created through the design and construction of a microfluidic device that relies on diffusion-based principles to apply different chemical compounds that have been shown to affect chondrocyte phenotypes, creating a cellular gradient in hypertrophy similar to what is observed at the osteochondral interface. This work will be used to inform the design of tissue engineered implants for articular cartilage repair. This award under the East Asia and Pacific Summer Institutes program supports summer research by a U.S. graduate student and is jointly funded by NSF and the Ministry of Science and Technology of China.