Growing matter: a review of growth in living systems

Living systems can grow, develop, adapt, and evolve. These phenomena are non-intuitive to traditional engineers and often difficult to understand. Yet, classical engineering tools can provide valuable insight into the mechanisms of growth in health and disease. Within the past decade, the concept of incompatible configurations has evolved as a powerful tool to model growing systems within the framework of nonlinear continuum mechanics. However, there is still a substantial disconnect between the individual disciplines, which explore the phenomenon of growth from different angles. Here we show that the nonlinear field theories of mechanics provide a unified concept to model finite growth by means of a single tensorial internal variable, the second order growth tensor. We review the literature and categorize existing growth models by means of two criteria: the microstructural appearance of growth, either isotropic or anisotropic; and the microenvironmental cues that drive the growth process, either chemical or mechanical. We demonstrate that this generic concept is applicable to a broad range of phenomena such as growing arteries, growing tumors, growing skin, growing airway walls, growing heart valve leaflets, growing skeletal muscle, growing plant stems, growing heart valve annuli, and growing cardiac muscle. The proposed approach has important biological and clinical applications in atherosclerosis, in-stent restenosis, tumor invasion, tissue expansion, chronic bronchitis, mitral regurgitation, limb lengthening, tendon tear, plant physiology, dilated and hypertrophic cardiomyopathy, and heart failure. Understanding the mechanisms of growth in these chronic conditions may open new avenues in medical device design and personalized medicine to surgically or pharmacologically manipulate development and alter, control, or revert disease progression.