The process of in situ tissue engineering aims to restore tissue homeostasis, both in composition and organization, after remodeling of newly formed extracellular matrix (ECM) and the resolution of inflammation. Resolving this response is complex and tightly regulated. A better understanding of the resolution phase is needed in order to steer this process towards the desired outcome. Key players are the immune system, matrix producing cells and matrix organization. Macrophages are thought to be one of the key regulators in the in situ regenerative response and their polarization into a spectrum of phenotypes is hypothesized to play an important role in tissue remodeling. The interplay between inflammation and matrix organization remains a causality dilemma: does isotropic organized tissue cause inflammation, or does inflammation cause isotropic organized tissue?
In this project, we aim to gain fundamental knowledge on how different macrophage phenotypes and matrix organizations interact with each other in order to investigate if and how we can harness inflammation and matrix organization during late stage in situ tissue engineering. To do so, we use 2D and 3D in vitro models, consisting of macrophages, fibroblasts and collagen fibers. The addition of constraints allows us to steer the matrix organization between anisotropic and isotropic. Next to trying to answer fundamental questions, a translational study using human tissue will help us to validate our previous results.