Strain-induced Collagen Organization at the Micro-level in Fibrin-based Engineered Tissue Constructs

Abstract

Full understanding of strain-induced collagen organization in complex tissue geometries to create tissues with predefined collagen architecture has not been achieved. This is mainly due to our limited knowledge of collagen remodeling in developing tissues. Here we investigate straininduced collagen (re)organization in fibrin based engineered tissues using nondestructive time-lapse imaging. The tissues start from a biaxially constrained myofibroblast-populated fibrin gel and are used to study: (A) remodeling from a static equi-biaxial loading condition to static uniaxial loading; and (B) remodeling of a biaxially constrained tissue under uniaxial cyclic straining before and after a change in strain direction. Under static conditions, collagen oriented parallel to the direction of strain, whereas under cyclic conditions the orientation in the constrained tissue was perpendicular to the direction of strain. It is concluded that due to the biaxial constraints the uniaxially, cyclically strained cells can exert forces in two directions and strain shield themselves. A subsequent change in the direction of cyclic straining resulted in a rapid reorientation of collagen at the tissue surface. Reorientation was significantly slower in deeper tissue layers, where tissue remodeling was dominated by contact guidance provided by the endogenous matrix. These findings emphasize the relevance of achieving a functional collagen organization right from the start of tissue culture.

Stromal Cells in Dense Collagen Promote Cardiomyocyte and Microvascular Patterning in Engineered Human Heart Tissue

“…Previous studies have shown that fibroblast and stromal cell populations remodel matrix and induce matrix alignment in response to uniaxial strain. [55][56][57] These aligned matrix proteins possibly serve as the topographical cues for the cardiomyocytes to align and mature. 44,58 Results from our composite constructs (Fig.…”

Large strain stimulation promotes extracellular matrix production and stiffness in an elastomeric scaffold model

“…Different forms of physical cues include ultrasound waves (Duarte 1983), electromagnetic fields (Bassett et al 1974), or physiologic pulsatile flow patterns (Hahn et al 2007). Collectively, these have led to mechanical conditioning as a widely recognized a highly relevant factor influencing tissue accretion, micro-structure, all affecting the bulk mechanical response (de Jonge et al 2013a; Engelmayr et al 2005; Engelmayr and Sacks 2008; Engelmayr et al 2006; Hasaneen et al 2005; Haseneen et al 2003; Huey and Athanasiou 2011; Kim et al 1999; Merryman et al 2007; Nerurkar et al 2011c; Rubbens et al 2009; Syedain and Tranquillo 2009; von Offenberg Sweeney et al 2004). …”

Engineering Fibrin-based Tissue Constructs from Myofibroblasts and Application of Constraints and Strain to Induce Cell and Collagen Reorganization

“…The described model system of cell-populated fibrin constructs has great potential for the study of cell and collagen (re)organization (de Jonge et al 15 ), e.g. to be used for tissue engineering purposes.…”