Tissue Engineering by Self-Assembly of Cells Printed into Topologically Defined Structures

Jakab, Károly; Norotte, Cyrille; Damon, Brook; Marga, Françoise; Neagu, Adrian; Besch‐Williford, Cynthia; Kachurin, Anatoly M.; Church, Kenneth H.; Park, Hyoungshin; Mironov, Vladimir; Markwald, Roger R.; Vunjak‐Novakovic, Gordana; Forgács, Gabor

doi:10.1089/ten.2007.0173

Cited by 265 publications

(67 citation statements)

References 42 publications

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“…Emulating these structures in hydrogels via bioprinting technique is of considerable interest not only for tissue engineering and organs on a chip, but also for hydrogel microfluidics, 10, 39, 40 self-healing biomaterials 24, 25, 41 and organ printing. 33, 42, 43 The field of hydrogel microfluidics has gained increased attention in recent years. 21, 44 The ability to explore cell behavior within 3D microenvironments under continuous flow condition has allowed researchers to explore physiologically relevant mechanisms in tissue-like microenvironments.…”

Section: Resultsmentioning

confidence: 99%

Hydrogel bioprinted microchannel networks for vascularization of tissue engineering constructs

et al. 2014

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Vascularization remains a critical challenge in tissue engineering. The development of vascular networks within densely populated and metabolically functional tissues facilitate transport of nutrients and removal of waste products, thus preserving cellular viability over a long period of time. Despite tremendous progress in fabricating complex tissue constructs in the past few years, approaches for controlled vascularization within hydrogel based engineered tissue constructs have remained limited. Here, we report a three dimensional (3D) micromolding technique utilizing bioprinted agarose template fibers to fabricate microchannel networks with various architectural features within photo cross linkable hydrogel constructs. Using the proposed approach, we were able to successfully embed functional and perfusable microchannels inside methacrylated gelatin (GelMA), star poly (ethylene glycol-co-lactide) acrylate (SPELA), poly (ethylene glycol) dimethacrylate (PEGDMA) and poly (ethylene glycol) diacrylate (PEGDA) hydrogels at different concentrations. In particular, GelMA hydrogels were used as a model to demonstrate the functionality of the fabricated vascular networks in improving mass transport, cellular viability and differentiation within the cell-laden tissue constructs. In addition, successful formation of endothelial monolayers within the fabricated channels was confirmed. Overall, our proposed strategy represents an effective technique for vascularization of hydrogel constructs with useful applications in tissue engineering and organs on a chip.

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Section: Resultsmentioning

confidence: 99%

Hydrogel bioprinted microchannel networks for vascularization of tissue engineering constructs

et al. 2014

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“…Multiple groups have proposed using cells and aggregates of cells along with ECM proteins as building blocks in organ building strategies based on inkjet printer technology Jakab et al, 2007;Mironov et al, 2003a,b;Smith et al, 2004) or based on simple packing and endothelialization of preformed collagen gel-cell modules (McGuigan and Sefton, 2006). Understanding and controlling tissue fusion and cell sorting is important for these strategies as they seek to build vascularized organs with complex shapes and multiple cell types.…”

Section: Discussionmentioning

confidence: 99%

“…For purposes of tissue engineering, it is important to understand and control tissue fusion because strategies are emerging to use cells and aggregates of cells as building units to create larger more complex 3D tissue structures. For example, tissue fusion is important in organ printing, a process whereby a modified inkjet printer extrudes small volumes of viable cells or cell aggregates along with extracellular matrix proteins (ECM) to build a 3D structure layer by layer Jakab et al, 2007;Mironov et al, 2003a;Wilson and Boland, 2003). Others are creating microscale modules of cells plus ECM and assembling these structures to create organoids that can be perfused in vitro (McGuigan and Sefton, 2006).…”

Section: Introductionmentioning

confidence: 99%

Controlling cell position in complex heterotypic 3D microtissues by tissue fusion

Rago

Dean

Morgan

2008

Biotech & Bioengineering

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Tissue fusion and cell sorting are processes fundamental to developmental biology with applications in tissue engineering. We have designed a fusion assay to investigate the factors governing the fusion of microtissues and the cell sorting that occurs after fusion. Normal human fibroblast (NHF) spheroids were self-assembled and cultured for 1, 4, or 7 days, then combined in trough shaped recesses. Over a 24-h period the spheroids fused to become a rod shaped microtissue and the kinetics and extent of fusion could be quantified by assessing rod contraction. By varying the amount of spheroid culture time prior to fusion (1-7 days), the rate of fusion, the coherence of the building units (as measured by fusion angle) and the steady state length of the structure could be easily controlled. Longer pre-culture times for the spheroids resulted in slower fusion, less coherence and increased length of rod microtissues. The fusion kinetics and steady length of rods formed by smaller versus larger spheroids ( approximately 100 vs. 300 microm diameter) were indistinguishable, even though smaller spheroids had twice the surface area and greater numbers of contacts between units. Both small and large spheroids were strongly influenced by spheroid pre-culture time. Pre-culture time could also be used to control cell sorting and cell position when combinations of NHFs and H35s, a rat hepatocyte cell line, were fused to form heterotypic microtissues. Control of fusion and cell position are important parameters for creating functional heterotypic microtissues as well as the use of microtissues as building units to create larger tissue structures.

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“…These difficulties, along with the increased understanding of developmental and morphogenetic processes, have led many groups towards the development of “self-assembly” approaches in which individual cells organize into multicellular subunits (e.g. spheroids, sheets or cylinders) [42-45]. The individual subunits further arrange themselves into larger tissue structures with little intervention, and in most cases, without the use of exogenous scaffolds [46, 47].…”

Section: Fundamentals Of Tissue Engineeringmentioning

confidence: 99%

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

et al. 2010

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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.

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Tissue Engineering by Self-Assembly of Cells Printed into Topologically Defined Structures

Cited by 265 publications

References 42 publications

Hydrogel bioprinted microchannel networks for vascularization of tissue engineering constructs

Hydrogel bioprinted microchannel networks for vascularization of tissue engineering constructs

Controlling cell position in complex heterotypic 3D microtissues by tissue fusion

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

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