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

Abstract

Biofabrication of living structures with desired topology and functionality requires the interdisciplinary effort of practitioners of the physical, life, medical and engineering sciences. Such efforts are being undertaken in many laboratories around the world. Numerous approaches are being pursued, such as those based on the use of natural or artificial scaffolds, decellularized cadaveric extracellular matrices and lately bioprinting. To be successful in this endeavor it is crucial to provide in vitro micro-environmental clues for the cells resembling those in the organism. Therefore scaffolds populated with differentiated cells or stem cells of increasing complexity and sophistication are being fabricated. However, scaffolds, no matter how sophisticated they are, can cause problems stemming from their degradation, eliciting immunogenic reactions and other a priori unforeseen complications. It is also being realized that ultimately the best approach is to rely on the self-assembly and self-organizing properties of cells and tissues and the innate regenerative capability of the organism itself, not just simply prepare tissue and organ structures in vitro followed by their implantation. Here we briefly review the different strategies for the fabrication of three-dimensional biological structures, in particular bioprinting. We detail a fully biological, scaffoldless, print-based engineering approach that uses self-assembling multicellular units as bioink particles and employs early developmental morphogenetic principles, such as cell sorting and tissue fusion.

Principles of the Kenzan Method for Robotic Cell Spheroid-Based Three-Dimensional Bioprinting

“…From the early days of this field it has been appreciated the difficulties generated by the use of a 'scaffold', and suggested the most rational alternative: using only cells and the matrix they secrete 15 . This bioprinting approach was vastly explored conceptually 29 , and computer modeled 17,30 . The attempted implementations use 'sacrificial' inorganic materials which permit limited cell-cell interaction, then being removed at a point in the process 15 .…”

3D Printing for Tissue Engineering Applications

“…These tissues are printing with the advantage of cell-cell adhesion and they can grow and evolve in their own natural ECM. That reduces inflammatory responses and increases the biocompatibility of the engineered tissue [21]. For self-assembly applications, cell aggregates are the bioinks for bioprinting.…”

Biofabrication: an overview of the approaches used for printing of living cells

“…In many ways, this could be viewed as a distinct bioprinting concept, rather than just an alternate bioprinting method. It has been the subject of several topical reviews and opinion pieces (Jakab et al 2010;Marga et al 2012;Mironov et al 2009b;Mironov et al 2007;Mironov et al 2006). …”