Controlled Tubular Unit Formation from Collagen Film for Modular Tissue Engineering

Abstract

Bottom-up or modular tissue engineering is one of the emerging approaches to prepare biomimetic constructs in vitro, involving fabrication of small tissue units as building blocks before assembling them into functional tissue constructs. Herein, we reported a microscale tissue engineering approach to generate tubular tissue units through cellular contractile force induced self-folding of cell-laden collagen films in a controllable manner. Self-folding of cell-laden collagen films was driven by film contraction resulted from intrinsic contractile property of adherent mammalian cells seeded in collagen films. We explored in detail independent effects of collagen gel concentration, cell density, and intrinsic cellular contractility on self-folding and tubular structure formation of cell-laden collagen films. Through both experiments and theoretical modeling, we further demonstrated the effectiveness of integrating ridge array structures onto the backside of collagen films in introducing structural anisotropy and thus controlling self-folding directions of collage films. Our approach of using ridge array structures to introduce mechanical anisotropy and thus promote tubular tissue unit formation can be extended to other biomaterial systems and thus provide a simple yet effective way to prepare tubular tissue units for modular tissue engineering applications.

Origami Biosystems: 3D Assembly Methods for Biomedical Applications

“…Strain engineering based on self‐rolling methods has been used to create a variety of 3D curved tissue scaffolds. These include single and multilayered rolls (Figure i,j) and vascular mimics . They highlight the advantages of origami approaches such as facile layering of different cells and matrix as is needed in several tissues including blood vessels, the ability to leverage state of the art 2D patterning techniques such as photopatterning, contact printing and soft‐lithography, and the ability for high‐throughput fabrication of curved and folded cellular geometries that can be hard to access by other methods.…”

Dry vs. wet: Properties and performance of collagen films. Part I. Mechanical behaviour and strain-rate effect

“…Films prepared from collagen solutions or dispersions find application in scaffolds for tissue regeneration (corneal and wound healing), devices for sustained release of hormones, dural substitutes, etc. (Collins et al, 1991;Maeda et al, 2001;Ber et al, 2005;Sang et al, 2017;Li et al, 2019;Liu et al, 2012Liu et al, , 2014. Recently, collagen films were also used in flexible electronics too (Moreno et al, 2015;Ghosh and Mandal, 2017) thanks to their flexibility, biocompatibility, biodegradability and piezoelectric behaviour (Fukada and Yasuda, 1964;Denning et al, 2014).…”

Dry vs. wet: Properties and performance of collagen films. Part II. Cyclic and time-dependent behaviours

“…This hierarchical order defines the complex viscoelastic behaviour of collagenous materials. Importantly, collagen films have significant applications in tissue regeneration such as corneal and wound healing (Ber et al, 2005;Sang et al, 2017;Li et al, 2019;Liu et al, 2012Liu et al, , 2014, substrates for sustained release of hormones (Maeda et al, 2001), dural substitutes (Collins et al, 1991), flexible electronics (Moreno et al, 2015;Ghosh and Mandal, 2017) etc. thanks to their biocompatibility, biodegradability, flexibility and mechanical strength (Lee and Mooney, 2001;Fratzl, 2008).…”