Perfused Organ Cell‐Dense Macrotissues Assembled from Prefabricated Living Microtissues

Ip, Blanche C.; Cui, Francis; Wilks, Benjamin T.; Murphy, John; Tripathi, Anubhav; Morgan, Jeffrey R.

doi:10.1002/adbi.201800076

Cited by 13 publications

(6 citation statements)

References 49 publications

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“…To explore the confined self‐organization of cells, we employed cell‐repellent agarose hydrogel templates to realize topography‐induced aggregation ( Scheme ). Using HepG2 cells (a human hepatoma carcinoma cell line) as a model system, stable cellular aggregates with defined shapes were obtained after adding the cells (5 × 10 6 cells mL −1 ) into hydrogel templates for a 24 h culture (Scheme a). Taking advantage of defined hydrogel templates with different shapes (Figure S2, Supporting Information), cellular aggregates with simple shapes were first obtained such as toroid, trigonal ring, quadrangular ring, and pentagonal ring, where the templates provided a confined space for the aggregation and further fusion of cells ( Figure a–d).…”

Section: Resultsmentioning

confidence: 99%

Topography‐Induced Cell Self‐Organization from Simple to Complex Aggregates

Luo

Meng

et al. 2019

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Self‐organization is a fundamental and indispensable process in a living system. To understand cell behavior in vivo such as tumorigenesis, 3D cellular aggregates, instead of 2D cellular sheets, have been employed as a vivid in vitro model for self‐organization. However, most focus on the macroscale wetting and fusion of cellular aggregates. In this study, it is reported that self‐organization of cells from simple to complex aggregates can be induced by multiscale topography through confined templates at the macroscale and cell interactions at the nanoscale. On the one hand, macroscale templates are beneficial for the organization of individual cells into simple and complex cellular aggregates with various shapes. On the other hand, the realization of these macro‐organizations also depends on cell interactions at the nanoscale, as demonstrated by the intimate contact between nanoscale pseudopodia stretched by adjacent frontier cells, much like holding hands and by the variation in the intermolecular interactions based on E‐cadherin. Therefore, these findings may be very meaningful for clarifying the organizational mechanism of tumor development, tissue engineering and regenerative medicine.

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Section: Resultsmentioning

confidence: 99%

Topography‐Induced Cell Self‐Organization from Simple to Complex Aggregates

Luo

Meng

et al. 2019

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“…Our approach represents a rapid and simple alternative for the bottom-up generation of scaffoldfree and well-organized artificial vascular beds at millimetric scale. In previous studies, millimetresized tissues have been commonly generated by using non-adhesive moulds [16,18,36] or coated plates [14,15], where spheroids are seeded on and allowed to aggregate. Although simple and inexpensive, these approaches often lead to formation of tissues with irregular sizes and geometries, displaying a low degree of organization due to random spheroid fusion [14,15].…”

Section: Discussionmentioning

confidence: 99%

“…For biomanufacturing more complex structures, single spheroids can be subsequently fused into larger constructs [13], but current methodologies still present several limitations. A few studies have reported the formation of spheroid-based constructs, with dimensions in the range of 0.1-2 cm, by promoting spheroids fusion using non-adhesive wells and channels [14][15][16][17][18] or directional magnetic fields [19,20]. However, such methods often create constructs of irregular sizes, where spheroids are randomly packed [14,15].…”

Section: Introductionmentioning

confidence: 99%

Directed self-assembly of spheroids into modular vascular beds for engineering large tissue constructs

et al. 2021

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Spheroids can be used as building-blocks for bottom-up generation of artificial vascular beds, but current biofabrication strategies are often time-consuming and complex. Also, pre-optimization of single spheroid properties is often neglected. Here, we report a simple setup for rapid biomanufacturing of spheroid-based patch-like vascular beds. Prior to patch assembly, spheroids combining mesenchymal stem/stromal cells (MSCs) and outgrowth endothelial cells (OECs) at different ratios (10:1; 5:1; 1:1; 1:5) were formed in non-adhesive microwells and monitored along 7 d. Optimal OEC retention and organization was observed at 1:1 MSC/OEC ratio. Dynamic remodelling of spheroids led to changes in both cellular and extracellular matrix components (ECMs) over time. Some OEC formed internal clusters, while others organized into a peripheral monolayer, stabilized by ECM and pericyte-like cells, with concomitant increase in surface stiffness. Along spheroid culture, OEC switched from an active to a quiescent state, and their endothelial sprouting potential was significantly abrogated, suggesting that immature spheroids may be more therapeutically relevant. Non-adhesive moulds were subsequently used for triggering rapid, one-step, spheroid formation/fusion into square-shaped patches, with spheroids uniformly interspaced via a thin cell layer. The high surface area, endothelial sprouting potential, and scalability of the developed spheroid-based patches make them stand out as artificial vascular beds for modular engineering of large tissue constructs.

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“…In terms of applications, the conjugation of 3D-printed liver tissues and microfluidic systems integrated with biosensors could enable real-time monitoring, thus introducing a new paradigm to the drug screening platform. Furthermore, micromanipulation technology could serve as one of the strategies to build volumetric liver tissue constructs ( Ip et al, 2018 ; Ayan et al, 2020 ). This technology enables the control of functional liver tissue blocks to assemble the blocks according to the predefined design; this is expected to efficiently produce volumetric liver tissues.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Review on Multicomponent Hydrogel Bioinks Based on Natural Biomaterials for Bioprinting 3D Liver Tissues

Kim

Lee

et al. 2022

Front. Bioeng. Biotechnol.

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Three-dimensional (3D)-printed in vitro tissue models have been used in various biomedical fields owing to numerous advantages such as enhancements in cell response and functionality. In liver tissue engineering, several studies have been reported using 3D-printed liver tissue models with improved cellular responses and functions in drug screening, liver disease, and liver regenerative medicine. However, the application of conventional single-component bioinks for the printing of 3D in vitro liver constructs remains problematic because of the complex structural and physiological characteristics of the liver. The use of multicomponent bioinks has become an attractive strategy for bioprinting 3D functional in vitro liver tissue models because of the various advantages of multicomponent bioinks, such as improved mechanical properties of the printed tissue construct and cell functionality. Therefore, it is essential to review various 3D bioprinting techniques and multicomponent hydrogel bioinks proposed for liver tissue engineering to suggest future directions for liver tissue engineering. Accordingly, we herein review multicomponent bioinks for 3D-bioprinted liver tissues. We first describe the fabrication methods capable of printing multicomponent bioinks and introduce considerations for bioprinting. We subsequently categorize and evaluate the materials typically utilized for multicomponent bioinks based on their characteristics. In addition, we also review recent studies for the application of multicomponent bioinks to fabricate in vitro liver tissue models. Finally, we discuss the limitations of current studies and emphasize aspects that must be resolved to enhance the future applicability of such bioinks.

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Perfused Organ Cell‐Dense Macrotissues Assembled from Prefabricated Living Microtissues

Cited by 13 publications

References 49 publications

Topography‐Induced Cell Self‐Organization from Simple to Complex Aggregates

Topography‐Induced Cell Self‐Organization from Simple to Complex Aggregates

Directed self-assembly of spheroids into modular vascular beds for engineering large tissue constructs

Review on Multicomponent Hydrogel Bioinks Based on Natural Biomaterials for Bioprinting 3D Liver Tissues

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