Quantitative characterization of 3D bioprinted structural elements under cell generated forces

Morley, Cameron; Ellison, Sarah; Bhattacharjee, Tapomoy; O'Bryan, Christopher S.; Zhang, Yifan; Smith, Kourtney F; Kabb, Christopher P.; Sebastian, Mathew; Moore, Ginger; Schulze, Kyle D.; Niemi, Sean R.; Sawyer, W. Gregory; Tran, David; Mitchell, Duane A.; Sumerlin, Brent S.; Flores, Catherine; Angelini, Thomas E.

doi:10.1038/s41467-019-10919-1

Cited by 82 publications

(44 citation statements)

References 42 publications

(43 reference statements)

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“…This new way of building is fully compatible with a range of existing synthetic strategies, including 3D printing. Indeed, researchers are beginning to quantify emergent material dynamics driven by cell behaviors within living bio-inks (32,33). These dynamics include compaction of relatively loose printed ECMs by resident cells, which can cause shrinkage, fracture, and shape change.…”

Section: Discussionmentioning

confidence: 99%

Kinomorphs: Shape-shifting tissues for developmental engineering

Viola

Porter

Gupta

et al. 2019

Preprint

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Current methods for building tissues usually start with a non-biological blueprint, or rely on self-organization, which does not extend to organ-scales. This has limited the construction of large tissues that simultaneously encode fine-scale cell organization. Here we bridge scales by mimicking developmental dynamics using “kinomorphs”, tissue scaffolds that undergo globally programmed shape and density changes to trigger local self-organization of cells in many locations at once. In this first report, we focus on mimicking the extracellular matrix (ECM) compaction and division into leaflets that occurs in kidney collecting duct development. We start by creating single-cell resolution cell patterns in ECM-mimetic hydrogels that are >10x larger than previously described, by leveraging photo-lithographic technology. These patterns are designed to mimic the branch geometry of the embryonic kidney collecting duct tree. We then predict the shape dynamics of kinomorphs driven by cell contractility-based compaction of the ECM using kinematic origami simulations. We show that these dynamics spur centimeter-scale assembly of structurally mature ~50 μm-diameter epithelial tubules that are locally self-organized, but globally programmed. Our approach prescribes tubule network geometry at ~5x smaller length-scales than currently possible using 3D printing, and at local cell densities comparable to in vivo tissues. Kinomorphs could be used to scaffold and “plumb” arrays of organoids in the future, by guiding the morphogenesis of epithelial networks. Such hybrid globally programmed/locally self-organized tissues address a major gap in our ability to recapitulate organ-scale tissue structure.Significance StatementEngineers are attempting to build tissues that mimic human diseases outside of the body. Although stem cells can be coaxed to form small organoids with a diversity of cell types, they do not properly organize over large distances by themselves. We report a strategy to mimic developmental processes using dynamic materials that attempt to guide a cellular “blueprint” towards a more complex tissue endpoint. We call these materials kinomorphs, combining the Greek kinó (propel, drive) and morfí (form, shape), since they seek to shepherd both the shape and developmental trajectory of cell collectives within them. Kinomorphs could pave the way towards organ-scale synthetic tissues built through a hybrid of engineering and self-organization strategies.

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Section: Discussionmentioning

confidence: 99%

Kinomorphs: Shape-shifting tissues for developmental engineering

Viola

Porter

Gupta

et al. 2019

Preprint

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“…[ 298 – 301 ] Next generation bioinks, in addition to design criteria centered on rheology and printability, will need to be inspired by substantial input from advances in cell biology and biotechnology. Fundamental lessons learned from embryonic development, mechanobiology, cell differentiation and repair in species with regenerative capacity superior to that of humans, [ 302 , 303 ] will be paramount to guide bioink development, as well as to instruct which architectures and cell patterns to print to boost maturation. Given the dynamic and multifaceted events that determine development and progress of living tissues, other important criteria will be endowing bioprinted structures with the ability to evolve over time and provide different stimuli to the printed cells, for instance via the incorporation of materials in which biological signals and growth factors can be patterned and released on demand.…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

From Shape to Function: The Next Step in Bioprinting

et al. 2020

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In 2013, the “biofabrication window” was introduced to reflect the processing challenge for the fields of biofabrication and bioprinting. At that time, the lack of printable materials that could serve as cell‐laden bioinks, as well as the limitations of printing and assembly methods, presented a major constraint. However, recent developments have now resulted in the availability of a plethora of bioinks, new printing approaches, and the technological advancement of established techniques. Nevertheless, it remains largely unknown which materials and technical parameters are essential for the fabrication of intrinsically hierarchical cell–material constructs that truly mimic biologically functional tissue. In order to achieve this, it is urged that the field now shift its focus from materials and technologies toward the biological development of the resulting constructs. Therefore, herein, the recent material and technological advances since the introduction of the biofabrication window are briefly summarized, i.e., approaches how to generate shape, to then focus the discussion on how to acquire the biological function within this context. In particular, a vision of how biological function can evolve from the possibility to determine shape is outlined.

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“… 27,32 The Angelini research group similarly have multiple publications, focusing on the physics of the embedded printing process, 35,36 new materials for the support bath, 26,37 and cell behavior in 3D environments. 38–40 Daly and co-workers have also explored 3D printing in yield-stress support baths using a range of chemistries and hydrogel microparticles. 41 The impact of FRESH printing is also apparent by the large number of research labs that have adopted the technique.…”

Section: The Emergence Of Fresh and Embedded 3d Printing Within The Bmentioning

confidence: 99%

“… 52 Additionally, several other research groups have modified the FRESH approach to create support baths from gellan gum, 53,54 laponite nanoclay, 53,55–58 and acrylamide. 38 A range of example support baths are shown in Fig. 4 and listed in Table II .…”

Section: Customizability Of the Fresh Platformmentioning

confidence: 99%

Emergence of FRESH 3D printing as a platform for advanced tissue biofabrication

et al. 2021

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In tissue engineering, an unresolved challenge is how to build complex 3D scaffolds in order to recreate the structure and function of human tissues and organs. Additive manufacturing techniques, such as 3D bioprinting, have the potential to build biological material with unprecedented spatial control; however, printing soft biological materials in air often results in poor fidelity. Freeform Reversible Embedding of Suspended Hydrogels (FRESH) is an embedded printing approach that solves this problem by extruding bioinks within a yield-stress support bath that holds the bioinks in place until cured. In this Perspective, we discuss the challenges of 3D printing soft and liquid-like bioinks and the emergence for FRESH and related embedded printing techniques as a solution. This includes the development of FRESH and embedded 3D printing within the bioprinting field and the rapid growth in adoption, as well as the advantages of FRESH printing for biofabrication and the new research results this has enabled. Specific focus is on the customizability of the FRESH printing technique where the chemical composition of the yield-stress support bath and aqueous phase crosslinker can all be tailored for printing a wide range of bioinks in complex 3D structures. Finally, we look ahead at the future of FRESH printing, discussing both the challenges and the opportunities that we see as the biofabrication field develops.

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Quantitative characterization of 3D bioprinted structural elements under cell generated forces

Cited by 82 publications

References 42 publications

Kinomorphs: Shape-shifting tissues for developmental engineering

Kinomorphs: Shape-shifting tissues for developmental engineering

From Shape to Function: The Next Step in Bioprinting

Emergence of FRESH 3D printing as a platform for advanced tissue biofabrication

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