Growth and remodeling of tissue structure and properties

Abstract

Soft biological tissues vary significantly in their mechanical properties, from the more rigid articular cartilage to the very soft and extensible skin and mesentery. Yet tissues are made of the same constituents: Fibers, muscle cells, non-muscle cells, and a fluid matrix. The key to diversity in properties is a parallel diversity in structure. The present study addressed the question of how is tissue structure determined? Living tissues have the unique ability to grow and remodel under altered mechanical loading by turnover of their fibers, where some are degraded and new ones are produced and deposited. It was hypothesized that tissue structure evolves with growth by remodeling its structure in response to growth-induced loading. The hypothesis was tested by structural simulation. The modeling framework developed is a multi-scale, micro-mechanical one, which integrates the effects of cells, fibers, and matrix, based solely on the biological processes in the remodeling tissue, thereby linking the constituents’ turnover to the evolving tissue structure and properties. The results are compatible with the evolved adult tissue structure and mechanical characteristics. Specifically, the theory predicts the evolution of well-known soft tissues features such as the nonuniform undulation of collagen fibers and associated tissue, nonlinear convex strain–stress response, and the evolution of growth-induced prestrain and prestress. These results support the notion that tissues’ structure and properties evolve as they grow.