A comprehensive framework for computational modeling of growth and remodeling in tissue-engineered soft collagenous materials.

Abstract

Developing clinically viable tissue-engineered structural cardiovascular implants-such as vascular grafts and heart valves-remains a formidable challenge. Achieving reliable and durable outcomes requires a deeper understanding of the fundamental mechanisms driving tissue evolution during in vitro maturation. Although considerable progress has been made in modeling soft tissue growth and remodeling, studies focused on the early stages of tissue engineering remain limited. Here, we present a general, thermodynamically consistent model to predict tissue evolution and mechanical response throughout the in vitro maturation of passive, load-bearing soft collagenous constructs. The formulation utilizes a stress-driven homeostatic surface to capture volumetric growth, coupled with an energy-based approach to describe collagen densification via the strain energy of the fibers. We further employ a co-rotated intermediate configuration to ensure the model's consistency and generality. The framework is demonstrated with two numerical examples: a uniaxially constrained tissue strip validated against experimental data and a cruciform-shaped biaxially constrained specimen subjected to load perturbation. These results highlight the potential of the proposed model to advance the design and optimization of tissue-engineered structural cardiovascular implants with clinically relevant performance.