Author: Lizzy Blaney
Background
Hydrogels are synthetic scaffolds that are fabricated to have mechanical and dynamic stiffness similar to the extracellular matrix of the original tissues. In a study involving GelMA hydrogels with different mechanical and biocompatible characteristics, the expected outcome was enhanced cellular process i.e. differentiation and migration. It was found that GelMA hydrogels exert a significant impact on cell adhesion, proliferation, and differentiation, as well as promoting swelling capability and enhancing spheroidal functionality. The stiffness of the gels was also found to constrain cellular events, meaning it could be tailored to promote specific functionality. As such, the gels used in this experiment are specifically designed to facilitate chondrocyte differentiation.
Hypotrophic Chondrocytes
Primarily characterized as dualistic cells, hypertrophic chondrocytes (bone cells) are cells found at junctions at the ends of bones within joints. Their main function is ossification and fracture healing, leading to their unique trait of occasional differentiation into osteoblasts. Primarily existing in direct contact with an extracellular matrix, there are three main types of chondrocytes: superficial zone, deep zone, and mineralized zone–which specifically express type X collagen and are the main focus of this experiment. While its functions are unknown, type X collagen is a key marker and indicator for progressive changes in cartilage growth and destruction. This is due to high apoptotic rates, which could potentially be due to an asymmetrical differentiation process (where in which one daughter cell becomes an osteoblast, and the other undergoes apoptosis). While the process of how hypertrophic chondrocytes could differentiate into osteoblasts is largely unclear, there is a strong potential for transdifferentiation or dedifferentiation.
Mechanics
The differentiation of cells is influenced and directed by the extracellular matrix, as seen by the fact that indirect STEM cell treatments revolve around changing the extracellular environment to stimulate growth. In an experiment by Engler and colleagues, it was found that matrix stiffness is a key factor in determining STEM cell lineage specification: softer stiffness matrices caused differentiation into neurogenic cells, medium stiffness matrices into myogenic cells, and high stiffness matrices into osteogenic cells. Thus, it was concluded that STEM cell transition specificity is based upon and influenced by matrix stiffness.
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