Biomimetic hydrogel supports initiation and growth of patient-derived breast tumor organoids

Prince, Elisabeth; Cruickshank, Jennifer; Ba-Alawi, Wail; Hodgson, Kate; Haight, Jillian; Tobin, Chantal; Wakeman, A. Maurice; Avoulov, Alona; Topolskaia, Valentina; Elliott, Mitchell J.; McGuigan, Alison P.; Berman, Hal K.; Haibe‐Kains, Benjamin; Cescon, David W.; Kumacheva, Eugenia

doi:10.1038/s41467-022-28788-6

Cited by 73 publications

(66 citation statements)

References 83 publications

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“…Interestingly the OT-2 workflow developed here was compatible with all three different viscous hydrogel compositions we used without the need for protocol adjustments. There is considerable effort within the community to generate biomatrix alternatives to replace commonly used Matrigel™ since it cannot be easily standardized [47,48]. Many of these alternative bio-matrices are viscous hydrogels or hydrogel precursors therefore automated tissue manufacturing methods compatible with these more viscous materials will likely be important as the use of these alternative gels increases [49].…”

Section: Resultsmentioning

confidence: 99%

An automation workflow for high-throughput manufacturing and analysis of scaffold-supported 3D tissue arrays

Cao

Cadavid

et al. 2022

Preprint

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The success rate of bringing novel cancer therapies to the clinic remains extremely low due to the lack of relevant pre-clinical culture models that capture the complexity of human tumours. Patient-derived organoids have emerged as a useful tool to model patient and tumour heterogeneity to begin addressing this need. Scaling these complex culture models while enabling stratified analysis of different cellular sub-populations remains a challenge, however. One strategy to enable higher throughput organoid cultures that also enables easy image-based analysis is the Scaffold-supported Platform for Organoid-based Tissues (SPOT) platform. SPOT allows the generation of flat, thin and dimensionally-defined microtissues in both 96- and 384-well plate footprints and is compatible with tumour organoid culture and downstream image-based readouts. SPOT manufacturing is currently a manual process however, limiting the use of SPOT to perform larger-scale screening. In this study, we integrate and optimize an automation approach to generate tumour-mimetic 3D engineered microtissues in SPOT using a liquid handler, and show comparable within-sample and between-sample variation as the standard manual manufacturing process. Furthermore, we develop a liquid handler-supported whole-cell extraction protocol and as a proof-of-value demonstration, we generate 3D complex tissues containing different proportions of tumour and stromal cells and perform single-cell-based end-point analysis to demonstrate the impact of co-culture on the tumour cell population specifically. We also demonstrate we can incorporate primary patient-derived organoids into the pipeline to capture patient-level tumour heterogeneity. We envision that this automated workflow integrated with 96/384-SPOT and multiple cell types and patient-derived organoid models will provide opportunities for future applications in high-throughput screening for novel personalized therapeutic targets. This pipeline also allows the user to assess dynamic cell responses using high-content longitudinal imaging or downstream single-cell-based analyses.

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Section: Resultsmentioning

confidence: 99%

An automation workflow for high-throughput manufacturing and analysis of scaffold-supported 3D tissue arrays

Cao

Cadavid

et al. 2022

Preprint

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“…Over the past decade, our group has developed microgels derived from alginate, agarose, ,, chitosan, and nanocellulose. − Recently, we developed a biomimetic filamentous hydrogel from aldehyde-functionalized cellulose nanocrystals (a-CNCs) chemically cross-linked with gelatin (later in the text, this gel is referred to as EKGel). − The a-CNCs were responsible for the fibrillar hydrogel structure and enabled control of the hydrogel stiffness, and gelatin provided cell-adhesion ligands. The EKGel offers the biocompatibility and the capability to control the chemical and physical hydrogel properties.…”

Section: Transformation Of Droplets To Microgelsmentioning

confidence: 99%

Trends in Droplet Microfluidics: From Droplet Generation to Biomedical Applications

et al. 2022

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Over the past decade, droplet microfluidics has attracted growing interest in biology, medicine, and engineering. In this feature article, we review the advances in droplet microfluidics, primarily focusing on the research conducted by our group. Starting from the introduction to the mechanisms of microfluidic droplet formation and the strategies for cell encapsulation in droplets, we then focus on droplet transformation into microgels. Furthermore, we review three biomedical applications of droplet microfluidics, that is, 3D cell culture, single-cell analysis, and in vitro organ and disease modeling. We conclude with our perspective on future directions in the development of droplet microfluidics for biomedical applications.

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“…Currently, the cultivation of PDOs relies on basement-membrane extract (BME), which suffers from batch-to-batch variability and poor control of mechanical properties. To address these issues, Prince et al [157] developed a nanofibrous hydrogel (EKGel) for the culture of breast cancer PDOs. PDOs grown in EKGel have similar histopathological features, gene expression, and drug responses to their parental tumors.…”

Section: Cancer Treatmentmentioning

confidence: 99%

Biocompatible Conductive Hydrogels: Applications in the Field of Biomedicine

Yang

Lin

Yang

et al. 2022

IJMS

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The impact of COVID-19 has rendered medical technology an important factor to maintain social stability and economic increase, where biomedicine has experienced rapid development and played a crucial part in fighting off the pandemic. Conductive hydrogels (CHs) are three-dimensional (3D) structured gels with excellent electrical conductivity and biocompatibility, which are very suitable for biomedical applications. CHs can mimic innate tissue’s physical, chemical, and biological properties, which allows them to provide environmental conditions and structural stability for cell growth and serve as efficient delivery substrates for bioactive molecules. The customizability of CHs also allows additional functionality to be designed for different requirements in biomedical applications. This review introduces the basic functional characteristics and materials for preparing CHs and elaborates on their synthetic techniques. The development and applications of CHs in the field of biomedicine are highlighted, including regenerative medicine, artificial organs, biosensors, drug delivery systems, and some other application scenarios. Finally, this review discusses the future applications of CHs in the field of biomedicine. In summary, the current design and development of CHs extend their prospects for functioning as an intelligent and complex system in diverse biomedical applications.

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Biomimetic hydrogel supports initiation and growth of patient-derived breast tumor organoids

Cited by 73 publications

References 83 publications

An automation workflow for high-throughput manufacturing and analysis of scaffold-supported 3D tissue arrays

An automation workflow for high-throughput manufacturing and analysis of scaffold-supported 3D tissue arrays

Trends in Droplet Microfluidics: From Droplet Generation to Biomedical Applications

Biocompatible Conductive Hydrogels: Applications in the Field of Biomedicine

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