Self-Organizing Tissue-Engineered Constructs in Collagen Hydrogels

Abstract

A novel self-organizing behavior of cellularized gels composed of collagen type 1 that may have utility for tissue engineering is described. Depending on the starting geometry of the tissue culture well, toroidal rings of cells or hollow spheroids were prompted to form autonomously when cells were seeded onto the top of gels and the gels released from attachment to the culture well 12 to 24 h after seeding. Cells within toroids assumed distinct patterns of alignment not seen in control gels in which cells had been mixed in. In control gels, cells formed complex three-dimensional arrangements and assumed relatively higher levels of heterogeneity in expression of the fibronectin splice variant ED-A—a marker of epithelial mesenchymal transformation. The tissue-like constructs resulting from this novel self-organizing behavior may have uses in wound healing and regenerative medicine, as well as building blocks for the iterative assembly of synthetic biological structures.

Stem Cell Recruitment After Injury: Lessons for Regenerative Medicine

“…Building upon earlier work suggesting that local delivery of BM-MSCs within a simple collagen matrix could support cellular engraftment following experimentally induced cardiac ischemia [180], more sophisticated methodologies have since utilized external BM-MSC seeding and directed collagen hydrogel contraction to form 3D cell-based constructs capable of augmenting contractile skin wound healing [181]. Additionally, BM-MSC seeding of a variety of scaffolds designed to mimic the microcomposition of native extracellular matrix has been used for the directive regeneration of a variety of tissues in vitro and in vivo , including bone [182–184], cartilage [179,185,186] and myocardium [187].…”

Constitutive modeling of compressible type-I collagen hydrogels

“…Cell-based compaction of hydrogels primarily involve observation of the changes in size or shape of the hydrogel and estimation of cell-generated traction forces from the known material behavior [13,15,42–45]. As mentioned earlier, interpretation of experimental results depends on the selection of a suitable material model that can perform under the conditions of interest.…”

“…Injectable collagen hydrogels are currently being investigated to stabilize and improve ventricle remodeling after myocardial infarction [11]. When physically loaded, (e.g., following implantation or when seeded with contractile cells) collagen gels undergo compression and compaction due to the collapse of aqueous voids within the material [12–15]. Accurate interpretation of the response of these materials to applied loads of these (e.g., using finite element analysis), requires the application of an appropriate constitutive model that captures the complex mechanical behavior.…”

Introduction: Extracellular Matrix and Cardiovascular Remodeling—Using Microscopy to Delineate Mechanisms

“…The Gourdie and Potts laboratories explored how self-organizing tissue constructs can be engineered. (Gourdie RG, 2012) Their article describes a novel self-organizing behavior of cellularized collagen I gels that may be useful in wound healing and regenerative medicine. The Baudino laboratory revealed how desmoplakin cell-cell interactions mediate cardiac cell functions, including cytokine secretion.…”

“…They show that in disease states, such as diabetes, heterotypic endothelial cell and pericyte interactions are key regulators in vascular basement membrane deposition, which is critical for vessel tube maturation. The Gourdie and Potts laboratories explored how self-organizing tissue constructs can be engineered (Gourdie et al, 2012). Their article describes a novel self-organizing behavior of cellularized collagen I gels that may be useful in wound healing and regenerative medicine.…”