Cell-scaffold interactions in artificial bone: regulation of collagen-I networks and focal adhesion complexes by biochemical and environmental cues

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Collagen-I is the major fibrous extracellular component of bone responsible for its ultimate tensile strength. In tissue engineering (TE) one of the most important issues is to get cells inter-connected via a strong and functional extracellular matrix (ECM) mimicking as closely as possible naturally occurring ECM geometry. What is still missing is (i) a versatile, high-resolution and non-invasive online method to evaluate and quantify different aspects of engineered ECM and (ii) deeper insights into the mechanism as to why cellular ECM production is enhanced in 3D cell-scaffold composites, putatively via enhanced focal adhesion (FA) linkages, unlike in the 2D setting. The goal within this project is to develop such methods with collagen-I producing and bone forming cells based on multiphoton imaging (MPI) technologies, to use those techniques to compare collagen-I production and organization capabilities in 2D- and 3D-seeded constructs, to link them to the number, extension and distribution of FA complexes and to monitor changes due to biomechanical treatment of the constructs. Our major work hypothesis is that biomechanical stability of engineered bone tissue constructs is directly encoded by the angular distribution and fibrillary geometry of ECM collagen fibers, and high stability occurs within more isotropic interwoven fibrils as a result of activation of increased FA complex formation with ascorbic acid playing a critical role in the regeneration of collagen-I with optimum fiber stability.