Characterization and modulation of the immune response in in situ cardiovascular tissue engineering
In situ tissue engineering has become a promising new technique to restore native tissue structure and function by providing a microenvironment necessary to promote tissue regeneration. A biodegradable synthetic starter matrix (scaffold) is introduced to the body to provide this microenvironment at the place of interest. By initiating an inflammatory response upon implantation, a natural wound healing process can be induced to regenerate new tissue. In time, the scaffold will be replaced by this newly formed tissue, resulting in a native, living tissue with growth potential and the capability of remodeling. Within this project, we particularly focus on using in situ tissue engineering to create living heart valves and arteries, as an alternative to the conventional heart valve and small diameter artery replacement therapies, which are accompanied by considerable decrease of life expectancy and therapy-induced complications.
In situ tissue regeneration employs the foreign body response to activate the regenerative capacity of the human body. Tissue regeneration is initiated by immune cells (neutrophils, monocytes, and macrophages) infiltrating the scaffold in the inflammatory phase, followed by recruitment of circulating progenitor cells in the proliferative phase. Extracellular matrix is formed and remodeled while the scaffold is degraded, resulting in resolution of inflammation. This is a very balanced reaction, in which the slightest inaccuracy results in non-functional tissue formation or fibrosis.
We aim to investigate the underlying mechanisms in these different phases, in particularly the role of macrophages (m1/m2 phenotype) and the types of cytokines and growth factors produced in situ. This knowledge can be used to design an instructive scaffold, which can act as a guidance for optimal tissue regeneration.