Articular cartilage is highly specified tissue with unique mechanical properties. These mechanical properties result from the extracellular matrix (ECM) components: the complex architecture of the collagen network, proteoglycans and water in the tissue. Collagen fibers extend millimeters from the underlying bone to bend over to lay flat on the articular surface forming the unique Benninghof arcade architecture. To achieve the desired properties in tissue engineered constructs, the development of a proper collagen structure is key to whether the tissue will function properly and not eventually break down. However, the mechanism responsible for the formation of the distinctive arcades has never been demonstrated nor replicated in tissue engineered cartilage.
The aim of this PhD project is to identify the postnatal growth mechanism of the collagen architecture, using previously developed cartilage organoid models, produced from human chondrocytes or progenitor cells. To understand the influence of the physical-chemical environment in tissue growth, the growth process will be perturbed in an in vitro culture system to create varying collagen architectures. Consequently, this knowledge will be used to create unique tissue growth environments to guide the formation of the desired collagen architectures in cartilage tissue engineering. In addition to molecular biological, biochemical, histological assessment methods, advanced microscopic methods will be used to visualize the collagen architecture.
This research is part of the Dutch Gravitation program Materials Driven Regeneration (MDR).