scholarly journals Aspiration-assisted Freeform Bioprinting of Tissue Spheroids in a Yield-stress Gel

2020 ◽  
Author(s):  
Bugra Ayan ◽  
Zhifeng Zhang ◽  
Nazmiye Celik ◽  
Kui Zhou ◽  
Yang Wu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Yield Stress ◽  
Self Assembly ◽  
Physical Mechanism ◽  
Three Dimensional ◽  
Human Mesenchymal Stem Cell ◽  
Self Healing ◽  
New Approach ◽  
Cell Spheroids ◽  
Cellular Aggregates

AbstractBioprinting of cellular aggregates, such as tissue spheroids or organoids, in complex three-dimensional (3D) arrangements has been a major obstacle for scaffold-free fabrication of tissues and organs. In this research, we unveiled a new approach to the bioprinting of tissue spheroids in a yield stress granular gel, which exhibited unprecedented capabilities in freeform positioning of spheroids in 3D. Due to its Herschel-Bulkley and self-healing properties as well as its biological inertness, the granular gel supported both the positioning and self-assembly of tissue spheroids. We studied the underlying physical mechanism of the approach to elucidate the interactions between the aspirated spheroids and the gel’s yield-stress during the transfer of spheroids from cell media to the gel. We demonstrate the application of the proposed approach in the realization of various freeform shapes and self-assembly of human mesenchymal stem cell spheroids for the construction of cartilage and bone tissues.

scholarly journals Aspiration-assisted freeform bioprinting of pre-fabricated tissue spheroids in a yield-stress gel

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Bugra Ayan ◽  
Nazmiye Celik ◽  
Zhifeng Zhang ◽  
Kui Zhou ◽  
Myoung Hwan Kim ◽  
...  
Keyword(s):  
Yield Stress ◽  
Self Assembly ◽  
Physical Mechanism ◽  
Three Dimensional ◽  
Human Mesenchymal Stem Cell ◽  
The Self ◽  
Self Healing ◽  
Cell Spheroids ◽  
On Demand ◽  
Cellular Aggregates

Abstract Bioprinting of cellular aggregates, such as tissue spheroids, to form three-dimensional (3D) complex-shaped arrangements, has posed a major challenge due to lack of robust, reproducible and practical bioprinting techniques. Here, we demonstrate 3D aspiration-assisted freeform bioprinting of tissue spheroids by precisely positioning them in self-healing yield-stress gels, enabling the self-assembly of spheroids for fabrication of tissues. The presented approach enables the traverse of spheroids directly from the cell media to the gel and freeform positioning of the spheroids on demand. We study the underlying physical mechanism of the approach to elucidate the interactions between the aspirated spheroids and the gel’s yield-stress during the transfer of spheroids from cell media to the gel. We further demonstrate the application of the proposed approach in the realization of various freeform shapes and self-assembly of human mesenchymal stem cell spheroids for the construction of cartilage and bone tissues.

scholarly journals Size-controlled human adipose-derived stem cell spheroids hybridized with single-segmented nanofibers and their effect on viability and stem cell differentiation

2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Jinkyu Lee ◽  
Sangmin Lee ◽  
Sung Min Kim ◽  
Heungsoo Shin
Keyword(s):  
Stem Cell ◽  
Cell Function ◽  
Average Length ◽  
Three Dimensional ◽  
Stem Cell Differentiation ◽  
Cell Spheroids ◽  
Significant Difference ◽  
Vitro Analysis ◽  
Physical And Chemical

Abstract Background Fabrication of three-dimensional stem cell spheroids have been studied to improve stem cell function, but the hypoxic core and limited penetration of nutrients and signaling cues to the interior of the spheroid were challenges. The incorporation of polymers such as silica and gelatin in spheroids resulted in relatively relaxed assembly of composite spheroids, and enhancing transport of nutrient and biological gas. However, because of the low surface area between cells and since the polymers were heterogeneously distributed throughout the spheroid, these polymers cannot increase the cell to extracellular matrix interactions needed to support differentiation. Methods We developed the stem cell spheroids that incorporate poly(ι-lactic acid) single-segmented fibers synthesized by electrospinning and physical and chemical fragmentation. The proper mixing ratio was 2000 cells/μg fibers (average length of the fibers was 50 μm - 100 μm). The SFs were coated with polydopamine to increase cell binding affinity and to synthesize various-sized spheroids. The function of spheroids was investigated by in vitro analysis depending on their sizes. For statistical analysis, Graphpad Prism 5 software (San Diego, CA, USA) was used to perform one-way analysis of variance ANOVA with Tukey’s honest significant difference test and a Student’s t-test (for two variables) (P < 0.05). Results Spheroids of different sizes were created by modulating the amount of cells and fibers (0.063 mm2–0.322 mm2). The fibers in the spheroid were homogenously distributed and increased cell viability, while cell-only spheroids showed a loss of DNA contents, internal degradation, and many apoptotic signals. Furthermore, we investigated stemness and various functions of various-sized fiber-incorporated spheroids. In conclusion, the spheroid with the largest size showed the greatest release of angiogenic factors (released VEGF: 0.111 ± 0.004 pg/ng DNA), while the smallest size showed greater effects of osteogenic differentiation (mineralized calcium: 18.099 ± 0.271 ng/ng DNA). Conclusion The spheroids incorporating polydopamine coated single-segmented fibers showed enhanced viability regardless of sizes and increased their functionality by regulating the size of spheroids which may be used for various tissue reconstruction and therapeutic applications.

scholarly journals Influence of collagen‐based integrin α 1 and α 2 mediated signaling on human mesenchymal stem cell osteogenesis in three dimensional contexts

2018 ◽  
Vol 106 (10) ◽  
pp. 2594-2604 ◽  
Author(s):  
Silvia M. Becerra‐Bayona ◽  
Viviana R. Guiza‐Arguello ◽  
Brooke Russell ◽  
Magnus Höök ◽  
Mariah S. Hahn
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Three Dimensional ◽  
Human Mesenchymal Stem Cell

scholarly journals Aspiration-assisted bioprinting for precise positioning of biologics

2020 ◽  
Vol 6 (10) ◽  
pp. eaaw5111 ◽  
Author(s):  
Bugra Ayan ◽  
Dong Nyoung Heo ◽  
Zhifeng Zhang ◽  
Madhuri Dey ◽  
Adomas Povilianskas ◽  
...  
Keyword(s):  
Self Assembly ◽  
Physical Mechanism ◽  
Single Cells ◽  
Three Dimensional ◽  
3D Bioprinting ◽  
Precise Control ◽  
3D Space ◽  
Magnitude Range ◽  
Wide Range ◽  
Order Of Magnitude

Three-dimensional (3D) bioprinting is an appealing approach for building tissues; however, bioprinting of mini-tissue blocks (i.e., spheroids) with precise control on their positioning in 3D space has been a major obstacle. Here, we unveil “aspiration-assisted bioprinting (AAB),” which enables picking and bioprinting biologics in 3D through harnessing the power of aspiration forces, and when coupled with microvalve bioprinting, it facilitated different biofabrication schemes including scaffold-based or scaffold-free bioprinting at an unprecedented placement precision, ~11% with respect to the spheroid size. We studied the underlying physical mechanism of AAB to understand interactions between aspirated viscoelastic spheroids and physical governing forces during aspiration and bioprinting. We bioprinted a wide range of biologics with dimensions in an order-of-magnitude range including tissue spheroids (80 to 600 μm), tissue strands (~800 μm), or single cells (electrocytes, ~400 μm), and as applications, we illustrated the patterning of angiogenic sprouting spheroids and self-assembly of osteogenic spheroids.

scholarly journals A stimuli-responsive, pentapeptide, nanofiber hydrogel for tissue engineering

2019 ◽  
Author(s):  
James D. Tang ◽  
Cameron Mura ◽  
Kyle J. Lampe
Keyword(s):  
Tissue Engineering ◽  
Self Assembly ◽  
Amyloid Fibrils ◽  
Culture Media ◽  
Solvent Accessibility ◽  
Three Dimensional ◽  
Building Blocks ◽  
Weight Percent ◽  
Oligodendrocyte Progenitor Cells ◽  
Self Healing

ABSTRACTShort peptides are uniquely versatile building blocks for self-assembly. Supramolecular peptide assemblies can be used to construct functional hydrogel biomaterials—an attractive approach for neural tissue engineering. Here, we report a new class of short, five-residue peptides that form hydrogels with nanofiber structures. Using rheology and spectroscopy, we describe how sequence variations, pH, and peptide concentration alter the mechanical properties of our pentapeptide hydrogels. We find that this class of seven unmodified peptides forms robust hydrogels from 0.2–20 kPa at low weight percent (less than 3 wt. %) in cell culture media, and undergoes shear-thinning and rapid self-healing. The peptides self-assemble into long fibrils with sequence-dependent fibrillar morphologies. These fibrils exhibit a unique twisted ribbon shape, as visualized by TEM and Cryo-EM imaging, with diameters in the low tens of nanometers and periodicities similar to amyloid fibrils. Experimental gelation behavior corroborates our molecular dynamics simulations, which demonstrate peptide assembly behavior, an increase in β-sheet content, and patterns of variation in solvent accessibility. Our Rapidly Assembling Pentapeptides for Injectable Delivery (RAPID) hydrogels are syringe-injectable and support cytocompatible encapsulation of oligodendrocyte progenitor cells (OPCs), as well as their proliferation and three-dimensional process extension. Furthermore, RAPID gels protect OPCs from mechanical membrane disruption and acute loss of viability when ejected from a syringe needle, highlighting the protective capability of the hydrogel as potential cell carriers for trans-plantation therapies. The tunable mechanical and structural properties of these supramolecular assemblies are shown to be permissive to cell expansion and remodeling, making this hydrogel system suitable as an injectable material for cell delivery and tissue engineering applications.

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