Toward engineering functional organ modules by additive manufacturing.

Tissue engineering is emerging as a possible alternative to methods aimed at alleviating the growing demand for replacement tissues and organs. A major pillar of most tissue engineering approaches is the scaffold, a biocompatible network of synthetic or natural polymers, which serves as an extracellular matrix mimic for cells. When the scaffold is seeded with cells it is supposed to provide the appropriate biomechanical and biochemical conditions for cell proliferation and eventual tissue formation.

Tissue engineering by self-assembly and bio-printing of living cells.

Biofabrication of living structures with desired topology and functionality requires the interdisciplinary effort of practitioners of the physical, life and engineering sciences. Such efforts are being undertaken in many laboratories around the world. Numerous approaches are pursued, such as those based on the use of natural or artificial scaffolds, decellularized cadaveric extracellular matrices and, most lately, bioprinting.

Cadherin adhesion, tissue tension, and noncanonical Wnt signaling regulate fibronectin matrix organization.

In this study we demonstrate that planar cell polarity signaling regulates morphogenesis in Xenopus embryos in part through the assembly of the fibronectin (FN) matrix. We outline a regulatory pathway that includes cadherin adhesion and signaling through Rac and Pak, culminating in actin reorganization, myosin contractility, and tissue tension, which, in turn, directs the correct spatiotemporal localization of FN into a fibrillar matrix. Increased mechanical tension promotes FN fibril assembly in the blastocoel roof (BCR), while reduced BCR tension inhibits matrix assembly.

Relating cell and tissue mechanics: implications and applications.

The Differential Adhesion Hypothesis (DAH) posits that differences in adhesion provide the driving force for morphogenetic processes. A manifestation of differential adhesion is tissue liquidity and a measure for it is tissue surface tension. In terms of this property, DAH correctly predicts global developmental tissue patterns.

Tissue engineering by self-assembly of cells printed into topologically defined structures.

Understanding the principles of biological self-assembly is indispensable for developing efficient strategies to build living tissues and organs. We exploit the self-organizing capacity of cells and tissues to construct functional living structures of prescribed shape. In our technology, multicellular spheroids (bio-ink particles) are placed into biocompatible environment (bio-paper) by the use of a three-dimensional delivery device (bio-printer).

Multiscale computational analysis of Xenopus laevis morphogenesis reveals key insights of systems-level behavior.

Background: Tissue morphogenesis is a complex process whereby tissue structures self-assemble by the aggregate behaviors of independently acting cells responding to both intracellular and extracellular cues in their environment. During embryonic development, morphogenesis is particularly important for organizing cells into tissues, and although key regulatory events of this process are well studied in isolation, a number of important systems-level questions remain unanswered. This is due, in part, to a lack of integrative tools that enable the coupling of biological phenomena across spatial and temporal scales.

Three-dimensional tissue constructs built by bioprinting.

Bioprinting is an evolving tissue engineering technology. It utilizes computer controlled three-dimensional printers for rapid and high-precision construction of three-dimensional biological structures. We employed discrete and continuous bioprinting to build three-dimensional tissue constructs.

The interplay of cell-cell and cell-matrix interactions in the invasive properties of brain tumors.

Impairment of tissue cohesion and the reorganization of the extracellular matrix are crucial events during the progression toward invasive cell phenotype. We studied the in vitro invasion patterns of nine brain tumor cell lines in three-dimensional collagen gels. Cell-cell and cell-matrix interactions were quantified and correlated with the expression level of specific molecules: N-cadherin, matrix metalloproteinases, and their inhibitor.

Role of physical mechanisms in biological self-organization.

Organs form during morphogenesis, the process that gives rise to specialized biological structures of specific shape and function in early embryonic development. Morphogenesis is under strict genetic control, but shape evolution itself is a physical process. Here we report the results of experimental and modeling biophysical studies on in vitro biological structure formation.

Organ printing: fiction or science.

Aggregates of living cells (i.e. model tissue fragments) under appropriate conditions fuse like liquid drops.

Engineering biological structures of prescribed shape using self-assembling multicellular systems.

Self-assembly is a fundamental process that drives structural organization in both inanimate and living systems. It is in the course of self-assembly of cells and tissues in early development that the organism and its parts eventually acquire their final shape. Even though developmental patterning through self-assembly is under strict genetic control it is clear that ultimately it is physical mechanisms that bring about the complex structures.