Mechanical homeostasis in tissue equivalents: a review

Abstract

There is substantial evidence that growth and remodeling of load bearing soft biological tissues is to a large extent controlled by mechanical factors. Mechanical homeostasis, which describes the natural tendency of such tissues to establish, maintain, or restore a preferred mechanical state, is thought to be one mechanism by which such control is achieved across multiple scales. Yet, many questions remain regarding what promotes or prevents homeostasis. Tissue equivalents, such as collagen gels seeded with living cells, have become an important tool to address these open questions under well-defined, though limited, conditions. This article briefly reviews the current state of research in this area. It summarizes, categorizes, and compares experimental observations from the literature that focus on the development of tension in tissue equivalents. It focuses primarily on uniaxial and biaxial experimental studies, which are well-suited for quantifying interactions between mechanics and biology. The article concludes with a brief discussion of key questions for future research in this field.

A computational framework for modeling cell–matrix interactions in soft biological tissues

“…6a, b may be viscoelasticity due to collagen fibers moving within culture media, which is not included in our model in detail, and due to an increasing stiffness of the gel due to progressed polymerization when being placed in an incubator at 37°C for longer times. Finally, subtle aspects on the subcellular scale that are not included in our model may affect the time to reach the homeostatic state substantially because it is well known that this time differs considerably for different cell types (Eichinger et al 2021).…”

“…To study the micromechanical foundations of mechanical homeostasis experimentally, tissue culture studies with cell-seeded collagen or fibrin gels have attracted increasing interest over the past decades (Eichinger et al 2021). Circular free-floating gels, when seeded with fibroblasts, exhibit a strong compaction over multiple days in culture due to cellular contractile forces (Simon et al 2012(Simon et al , 2014.…”

“…If the gel is perturbed in phase II, for example, by an externally imposed deformation, cells appear to promote a restoration of the homeostatic state (Brown et al 1998;Ezra et al 2010). Despite substantial research efforts over decades, the exact interplay between cells and surrounding tissue that is crucial for mechanical homeostasis and other related phenomena such as durotaxis still remains poorly understood (Eichinger et al 2021).…”

Global Sensitivity Analysis of a Homogenized Constrained Mixture Model of Arterial Growth and Remodeling

“…Note, that there is a linear dependence between half-life and turnover time by a factor of ln 2. The exact nature of the homeostatic state of soft tissue remains controversial to date [47,[89][90][91]. Thus only little information is available about a reasonable range for σ h .…”

Soft Polymer-Based Technique for Cellular Force Sensing

“…The setup will inevitably disturb the normal cellular processes, adding uncertainties to the result and increasing infection in the measuring process. Moreover, axially constrained cellular force measurements, such as CFM experiments, often have a limited measurement time due to the eventual mechanical homeostasis [ 100 ]. Additionally, as the force is acquired from a discrete amount of force transducers, the interpretation of the result is dependent mainly on the transducer placement.…”