Evaluating chondrogenesis in a dish using engineered 3D microtissues

Articular cartilage has limited healing capacity, and its degradation over time leads to osteoarthritis, which is the leading cause of pain and disability in the US.  Scientists around the world are working to develop strategies to either extend the functional life of cartilage or to repair damaged cartilage.  The aim of this project is to explore how small molecules and growth factors influence stem cell capacity to regenerate cartilage.  

Cell culture devices, coupled with the right atmospheric and biochemical conditions, can help mimic a more physiologically relevant microenvironment for organogenesis or tissue development. Our team has developed a custom cell culture device that allows for the high throughput manufacture of uniform cartilage microtissues. Cultivation in this platform, called the “Microwell-mesh”, permits cells to self-organize and generate extracellular matrix in 3D, mimicking the cartilage development process. 

Robey group: The NIDCRs’ Skeletal Biology Section works with several different cell types that have chondrogenic differentiation potential including articular chondrocytes, bone marrow stromal cells (BMSC), and induced pluripotent stem cells (iPSC). These cell types can be used to generate the building blocks for tissue engineered cartilage or to screen for factors that enhance chondrogenesis. Despite these cells’ potential to contribute to cartilage regeneration, the biology of each cell type is complex, and there is much work to be done in order to develop a viable therapy.

Ferrer group: The NCATS’ intramural 3-D Tissue Bioprinting Laboratory, is a multidisciplinary group within NCATS’ Division of Preclinical Innovation that produces, validates and uses 3-D biofabricated tissues for disease modeling and drug discovery.

The BMES-SIP student will work with the NIDCR and NCATS team to generate cartilage-like tissues in custom cell culture devices and evaluate factors that may improve the differentiation process. These factors may be from a chemical compound library, recombinantly produced proteins or peptides, or resulting from gene modification. The student will setup cell cultures and use common assays to evaluate the quality of the cartilage-like microtissues including microscopy, histology, gene expression, and biochemical analysis.