New Tools for Understanding Extracellular Matrix Remodeling at the Micro-Level in Cardiovascular Tissue Engineering

Cardiovascular tissues have a prominent load-bearing function. Collagen fibers in the extracellular matrix provide strength to these tissues. In particular the content and organization of these fibers contribute to overall strength [1]. In case of changes in mechanical demand, collagen content and organization can be adapted, a process referred to as remodeling. Collagen is therefore a key factor when creating load-bearing tissues via tissue engineering (TE). In order to optimize TE constructs we want to control the collagen content and organization, by either mechanical conditioning of the construct [2] or modification of scaffold properties (degradation, structure) [3, 4]. In mechanically-induced remodeling via conditioning strategies in bioreactors, collagen and cells are generally seen as the key players [5]. Collagen is able to bear the load applied on a tissue; cells sense and react to this load [6, 7]. In cardiovascular TE myofibroblasts are the cells of main interest. Myofibroblasts are mechano-sensitive and mechanically inducible [1], and contribute to alterations in the overall collagen architecture. To be able to optimize and control the collagen architecture and remodeling, via mechanical conditioning or scaffolds, an understanding of underlying mechanisms is needed specifically. Our aim is to provide new tools to study remodeling phenomena. Therefore we developed a 3D in vitro model system to study collagen remodeling at the micro level in real-time. Here we apply the model to investigate remodeling in tissues engineered without a carrier material, or scaffold.