Degree of scaffold degradation influences collagen (re)orientation in engineered tissues

Tissue engineering provides a promising tool for creating load-bearing cardiovascular tissues. Ideally, the neotissue produced by cells possesses native strength and anisotropy. By providing contact-guiding cues with microfibers, scaffold directionality can guide tissue organization. However, scaffolds transiently degrade, which may induce undesired tissue remodeling in response to applied strain. We hypothesize that in newly formed tissues, the collagen matrix does not yet provide contact guidance to the cells, and collagen orientation is altered via strain-induced remodeling. To test this hypothesis, we studied the influence of lipase-induced scaffold degradation on collagen (re)orientation at static constraint. Myofibroblasts were cultured in electrospun PCL-U4U anisotropic microfiber scaffolds, which were statically constrained perpendicular to the scaffold fibers. During 2 weeks of culture, neotissue formation aligned in the direction of the scaffold fibers, after which scaffolds were degraded to different degrees (12%, 27%, and 79% reduction in scaffold weight) and collagen (re)orientation was studied after one additional week of culturing. High degrees of scaffold degradation (79%) were associated with remodeling of the collagen toward the constraint direction, while collagen organization was maintained at low degrees of scaffold degradation. These results highlight the importance of slow scaffold degradation when aiming at maintaining collagen orientation.