Confined cartilage: guiding growth for better joint repair Damage to articular cartilage affects millions, yet remains notoriously difficult to repair. This is because cartilage has a unique structural organization that current treatments fail to restore. This research will combine stem cells, hydrogel materials, and advanced imaging techniques to study how this structural organization develops in tiny cartilage building blocks as they are guided to grow and fuse in specific directions. By better understanding and controlling this process, this research will contribute to improved cartilage repair strategies, ultimately offering more effective and long-lasting solutions for patients with joint injuries.

Biomineralization is a marvel of natural ingenuity that enables forming hard biological tissues, such as bone, but is also implicated in disease, such as soft tissue calcification. Achieving engineering control over mineralization using environmental cues could have far-reaching implications in regenerative medicine, e.g. to engineer complex mineralized tissue interfaces. However, it remains largely unclear how spatiotemporal mineralization is controlled in 3D evolving tissues, and how this is affected by environmental cues. In particular, the role of mesoscale geometrical cues, which have recently attracted great interest due to their ability to controllably steer cell- and tissue-level response, on mineralization remains elusive. Therefore, I will study bone tissue mineralization in dynamic, mesoscale, mechano-geometric environments by combining rational design strategies, high-resolution microfabrication, novel in vitro culture platforms, and state-of-the-art interface characterization techniques, such as quantitative Raman imaging and analytical electron microscopy. This interdisciplinary approach will provide novel insights on the mineral formation in geometrically constrained tissues, which will subsequently be leveraged to design mesoscale-structured surfaces that enable tunable mineralization control, including the formation of spatial mineralization gradients. As such, this project will advance fundamental understanding of the mechanobiology of biomineralization, and will push the frontiers of instructive biomaterial design for tissue engineering.