Life is 3D: Boosting Spheroid Function for Tissue Engineering

Laschke, Matthias W.; Menger, Michael D.

doi:10.1016/j.tibtech.2016.08.004

Cited by 313 publications

(278 citation statements)

References 84 publications

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“…Three‐dimensional cell culture technologies provide physiologically relevant and, likely, more predictive strategies for organogenesis and tissue engineering, organs‐on‐a‐chip, drug discovery and testing, disease modeling, and developing cell‐based assays and animal‐free models . Three‐dimensional cellular systems, mimicking the native tissue structures, have been a noticeable improvement over two‐dimensional (2D) monolayer cultures in terms of improved cell–cell and cell–ECM interactions, high stability, and enhanced functionality (Figure ) .…”

Section: Introductionmentioning

confidence: 99%

Gelatin‐polysaccharide composite scaffolds for 3D cell culture and tissue engineering: Towards natural therapeutics

Afewerki

Sheikhi

Kannan

et al. 2018

Bioengineering & Transla Med

262

192

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Gelatin is a promising material as scaffold with therapeutic and regenerative characteristics due to its chemical similarities to the extracellular matrix (ECM) in the native tissues, biocompatibility, biodegradability, low antigenicity, cost‐effectiveness, abundance, and accessible functional groups that allow facile chemical modifications with other biomaterials or biomolecules. Despite the advantages of gelatin, poor mechanical properties, sensitivity to enzymatic degradation, high viscosity, and reduced solubility in concentrated aqueous media have limited its applications and encouraged the development of gelatin‐based composite hydrogels. The drawbacks of gelatin may be surmounted by synergistically combining it with a wide range of polysaccharides. The addition of polysaccharides to gelatin is advantageous in mimicking the ECM, which largely contains proteoglycans or glycoproteins. Moreover, gelatin–polysaccharide biomaterials benefit from mechanical resilience, high stability, low thermal expansion, improved hydrophilicity, biocompatibility, antimicrobial and anti‐inflammatory properties, and wound healing potential. Here, we discuss how combining gelatin and polysaccharides provides a promising approach for developing superior therapeutic biomaterials. We review gelatin–polysaccharides scaffolds and their applications in cell culture and tissue engineering, providing an outlook for the future of this family of biomaterials as advanced natural therapeutics.

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Section: Introductionmentioning

confidence: 99%

Gelatin‐polysaccharide composite scaffolds for 3D cell culture and tissue engineering: Towards natural therapeutics

Afewerki

Sheikhi

Kannan

et al. 2018

Bioengineering & Transla Med

262

192

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“…In one category, cells cultured by the 3D systems could become multicellular aggregates, also known as multicellular spheroids or spheroids. Spheroids generated by different methods have already been utilized in the field of stem cell biology and tissue engineering . In this review, we will provide an overview of biomaterial substrate‐derived spheroids and their applications in tissue engineering.…”

Section: Introductionmentioning

confidence: 99%

Biomaterial Substrate‐Mediated Multicellular Spheroid Formation and Their Applications in Tissue Engineering

Tseng

Wong

Hsieh

et al. 2017

Biotechnology Journal

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Three-dimentional (3D) multicellular aggregates (spheroids), compared to the traditional 2D monolayer cultured cells, are physiologically more similar to the cells in vivo. So far there are various techniques to generate 3D spheroids. Spheroids obtained from different methods have already been applied to regenerative medicine or cancer research. Among the cell spheroids created by different methods, the substrate-derived spheroids and their forming mechanism are unique. This review focuses on the formation of biomaterial substrate-mediated multicellular spheroids and their applications in tissue engineering and tumor models. First, the authors will describe the special chitosan substrate-derived mesenchymal stem cell (MSC) spheroids and their greater regenerative capacities in various tissues. Second, the authors will describe tumor spheroids derived on chitosan and hyaluronan substrates, which serve as a simple in vitro platform to study 3D tumor models or to perform cancer drug screening. Finally, the authors will mention the self-assembly process for substrate-derived multiple cell spheroids (co-spheroids), which may recapitulate the heterotypic cell-cell interaction for co-cultured cells or crosstalk between different types of cells. These unique multicellular mono-spheroids or co-spheroids represent a category of 3D cell culture with advantages of biomimetic cell-cell interaction, better functionalities, and imaging possibilities.

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“…Several technical advancements have been made to improve the fidelity of such in vitro systems. For example, the advent of three‐dimensional culture systems has yielded tremendous insights in biology that were previously difficult or impossible to observe with traditional two‐dimensional culture systems (Kolesky, Homan, Skylar‐Scott, & Lewis, ; Laschke & Menger, ). Moreover, the use of perfusion devices, which can deliver media throughout a tissue construct, has been instrumental in overcoming the limits of gas and nutrient diffusion that would otherwise lead to necrosis (Gao et al., ; Huang et al., ; Karimi et al., ; Prodanov et al., ; Roberts, DiVito, Ligler, Adams, & Daniele, ; Zhang, Wang, Hui, Qiu, & Wang, ).…”

Section: Commentarymentioning

confidence: 99%

Spatiotemporal Control of Morphogen Delivery to Pattern Stem Cell Differentiation in Three‐Dimensional Hydrogels

O’Grady

Balikov

Lippmann

et al. 2019

CP Stem Cell Biology

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Morphogens are biological molecules that alter cellular identity and behavior across both space and time. During embryonic development, morphogen spatial localization can be confined to small volumes in a single tissue or permeate throughout an entire organism, and the temporal effects of morphogens can range from fractions of a second to several days. In most cases, morphogens are presented as a gradient to adjacent cells within tissues to pattern cell fate. As such, to appropriately model development and build representative multicellular architectures in vitro, it is vital to recapitulate these gradients during stem cell differentiation. However, the ability to control morphogen presentation within in vitro systems remains challenging. Here, we describe an innovative platform using channels patterned within thick, three‐dimensional hydrogels that deliver multiple morphogens to embedded cells, thereby demonstrating exquisite control over both spatial and temporal variations in morphogen presentation. This generalizable approach should have broad utility for researchers interested in patterning in vitro tissue structures. © 2019 by John Wiley & Sons, Inc.

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Life is 3D: Boosting Spheroid Function for Tissue Engineering

Cited by 313 publications

References 84 publications

Gelatin‐polysaccharide composite scaffolds for 3D cell culture and tissue engineering: Towards natural therapeutics

Gelatin‐polysaccharide composite scaffolds for 3D cell culture and tissue engineering: Towards natural therapeutics

Biomaterial Substrate‐Mediated Multicellular Spheroid Formation and Their Applications in Tissue Engineering

Spatiotemporal Control of Morphogen Delivery to Pattern Stem Cell Differentiation in Three‐Dimensional Hydrogels

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