MECHANICAL AND TOPOLOGICAL CUES TO ENHANCE DE NOVO EXTRACELLULAR MATRIX ELABORATION IN ELASTOMERIC SCAFFOLD MODELS.

Jun 28, 2022, 11:20 AM
20m
Room: S3 A

Room: S3 A

Speaker

D'Amore, Antonio (Ri.MED Foundation/University of Pittsburgh)

Description

Elastomeric biodegradable scaffolds have been utilized as viable cardiovascular tissue surrogates in various applications, including cardiac patches, engineered vascular grafts, and heart valves. The interactions between cells and scaffold constitute an essential element in endogenous tissue growth and de novo tissue formation. Mechanical conditioning regimens are widely recognized as effective methods for facilitating extracellular matrix (ECM) accretion and improving engineered construct mechanical properties. Despite these advantageous factors, the understanding of the underlying cells - matrix interaction mechanisms remains relatively limited, hampering the development of in silico and in vitro models and the translation of engineered tissues into clinical application. In an attempt to reduce this gap in knowledge, we investigated how mechanical strain and micro-architecture impact ECM formation and elaboration. Vascular smooth muscle cells (VSMCs) have been micro-integrated into elastomeric biodegradable polyurethane scaffolds having identical microstructure. The constructs have been dynamically conditioned using a uniaxial stretch bioreactor for 21 days. Different levels of uniaxial strain, 15, 30, and 50%, have been continuously imposed at 1Hz of frequency for the entire culture period. We hypothesized that specific levels of strain and micro-architectures could be identified to enhance ECM production in quantity (collagen mass) and quality (anisotropy, stiffness). Samples were processed to evaluate ECM biosynthesis via: biochemical assay, qualitative and quantitative histological assessment, multi-photon analysis, and mechanical characterization. Experimental evaluation was coupled to a numerical model that elucidated the relationship between the scaffold micro-architecture and the strain acting on the cells. Results showed that while a 30% peak of strain level achieved maximum ECM synthesis rate, further increases in strain level led to a reduction in ECM. Likewise, micro-integrated scaffolds fabricated with different micro-architecture (i.e., different number of fibers intersections/area) have been exposed to 21 days of dynamic culture at a fixed 30% strain and a frequency of 1 Hz. Results highlighted the existence of specific micro-architectures and how topological cues are able to maximize ECM elaboration given a specific imposed macroscopic mechanical load. The improved understanding of the complex process of ECM formation in these mechanosensitive cell-scaffold models might lead to a more effective engineering and processing of cardiovascular tissue surrogates that are requested to function in highly demanding mechanical in-vivo environments.

20967803906

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