Tissue-to-Cellular Deformation Coupling in Cell-Microintegrated Elastomeric Scaffolds

Long term efficacy of tissue replacements or regenerative therapies rely on the critical processes of cell proliferation and differentiation, the production of organized matrix, and concurrent tissue remodeling or growth. Recent studies have shown that mechanical and chemical factors modulate cell function which has profound implications on tissue growth and remodeling. As such, creating engineered tissue replacement options requires a detailed command of the complex, dynamic, and reciprocal interactions which occur at the cell-ECM interface. To gain a better understanding of the coupled tissue-cellular deformation response, we propose the use of cell-microintegrated elastomeric scaffolds which provide a unique platform to investigate cellular deformations within a three dimensional fibrous scaffold. Scaffold specimens micro-integrated with vascular smooth muscle cells (VSMC) were subjected to controlled biaxial stretch with 3D cellular deformations and local fiber micro-architecture simultaneously quantified. Interestingly, local cellular deformations exhibited a non-linear deformation response with scaffold strain which was attributed to unique microarchitectural morphologies. Local scaffold microstructural changes induced by macro-level applied strain dominated cellular deformations, so that monotonic increases in scaffold strain do not necessitate similar levels of cellular deformation. This result has fundamental implications when attempting to elucidate the events of de-novo tissue development and remodeling in engineeredtissues.