Abstract
3D organoids are widely used as tractable in vitro models capable of elucidating aspects of human development and disease. However, the manual and low-throughput culture methods, coupled with a low reproducibility and geometric heterogeneity, restrict the scope and application of organoid research. Combining expertise from stem cell biology and bioengineering offers a promising approach to address some of these limitations. Here, melt electrospinning writing is used to generate tuneable grid scaffolds that can guide the self-organization of pluripotent stem cells into patterned arrays of embryoid bodies. Grid geometry is shown to be a key determinant of stem cell self-organization, guiding the position and size of emerging lumens via curvature-controlled tissue growth. Two distinct methods for culturing scaffold-grown embryoid bodies into either interconnected or spatially discrete cerebral organoids are reported. These scaffolds provide a high-throughput method to generate, culture, and analyze large numbers of organoids, substantially reducing the time investment and manual labor involved in conventional methods of organoid culture. It is anticipated that this methodological development will open up new opportunities for guiding pluripotent stem cell culture, studying lumenogenesis, and generating large numbers of uniform organoids for high-throughput screening.
| Original language | English |
|---|---|
| Article number | 2300305 |
| Number of pages | 14 |
| Journal | Advanced Materials |
| Volume | 35 |
| Issue number | 41 |
| DOIs | |
| Publication status | Published - 12 Oct 2023 |
| Externally published | Yes |
Funding
K.I.R.‐R. and S.J.P.C. contributed equally to this work. K.I.R‐R. and M.M.S. acknowledge funding through the EPSRC Centre for Doctoral Training in Neurotechnology (EP/L016737/1) and the Rosetrees Trust. S.J.P.C. acknowledges funding through a Rubicon fellowship from the Dutch Research Council (File No. 019.211EN.025) and through a UKRI Postdoctoral Fellowship (EP/X027163/1). R.X. and M.M.S. acknowledge funding from the Engineering and Physical Sciences Research Council (EP/P00114/1). M.C. acknowledges funding through a Swiss National Science Foundation PostDoc Mobility grant (P2EZP2_199862) and the L'Oreal‐UNESCO UK & Ireland For Women in Science Foundation. C.L.G. was supported by grants from StratNeuro and the Whitaker International Program. C.L.G. and M.M.S. acknowledge support from the Swedish Research Council (VR 4‐478/2016). L.P.‐M. acknowledges support from The Leverhulme Trust's “Leverhulme Doctoral Scholarship Programme” and the Engineering and Physical Research Council (Grant Number: EP/S023518/1). R.W. acknowledges funding from The Rosetrees Trust under the Young Enterprise Fellowship agreement (A2741/M873) and the British Heart Foundation under the Centre of Research Excellence agreement (RE/18/4/34215). A.C.M. acknowledges support from the Whitaker International Program. A.C.M. and M.M.S. acknowledge funding through the UK Regenerative Medicine Platform 'Acellular/Smart Materials‐3D Architecture (MR/R015651/1), Wellcome Trust Accelerator for Muscoskeletal Devices iTPA (208858/Z/17/Z), and National Institute for Health Global Health Research “POsT Conflict Trauma” (PrOTeCT 1613745). J.P.K.A. acknowledges funding from an MRC/UKRI Innovation Rutherford Fund Fellowship (MR/S00551X/1) and a UKRI Future Leaders Fellowship (MR/V024965/1). M.M.S. acknowledges support from the Wellcome Trust Senior Investigator Award (098411/Z/12/Z). Work in the Knoblich laboratory is supported by the Austrian Academy of Sciences, the Austrian Science Fund (FWF) (SCORPION DOC 72‐B27, Special Research Programme F7804‐B and Stand‐Alone grants P35680 and P35369), the Austrian Federal Ministry of Education, Science and Research, the City of Vienna, the Simons Foundation Autism Research Initiative (SFARI, no. 724430), and a European Research Council (ERC) Advanced Grant under the European Union's Horizon 2020 programs (no. 695642 and no. 874769). The authors acknowledge the use of the characterization facilities within the Harvey Flower Electron Microscopy Suite (Department of Materials) and the Facility for Imaging by Light Microscopy (FILM) at Imperial College London. K.I.R.-R. and S.J.P.C. contributed equally to this work. K.I.R-R. and M.M.S. acknowledge funding through the EPSRC Centre for Doctoral Training in Neurotechnology (EP/L016737/1) and the Rosetrees Trust. S.J.P.C. acknowledges funding through a Rubicon fellowship from the Dutch Research Council (File No. 019.211EN.025) and through a UKRI Postdoctoral Fellowship (EP/X027163/1). R.X. and M.M.S. acknowledge funding from the Engineering and Physical Sciences Research Council (EP/P00114/1). M.C. acknowledges funding through a Swiss National Science Foundation PostDoc Mobility grant (P2EZP2_199862) and the L'Oreal-UNESCO UK & Ireland For Women in Science Foundation. C.L.G. was supported by grants from StratNeuro and the Whitaker International Program. C.L.G. and M.M.S. acknowledge support from the Swedish Research Council (VR 4-478/2016). L.P.-M. acknowledges support from The Leverhulme Trust's “Leverhulme Doctoral Scholarship Programme” and the Engineering and Physical Research Council (Grant Number: EP/S023518/1). R.W. acknowledges funding from The Rosetrees Trust under the Young Enterprise Fellowship agreement (A2741/M873) and the British Heart Foundation under the Centre of Research Excellence agreement (RE/18/4/34215). A.C.M. acknowledges support from the Whitaker International Program. A.C.M. and M.M.S. acknowledge funding through the UK Regenerative Medicine Platform 'Acellular/Smart Materials-3D Architecture (MR/R015651/1), Wellcome Trust Accelerator for Muscoskeletal Devices iTPA (208858/Z/17/Z), and National Institute for Health Global Health Research “POsT Conflict Trauma” (PrOTeCT 1613745). J.P.K.A. acknowledges funding from an MRC/UKRI Innovation Rutherford Fund Fellowship (MR/S00551X/1) and a UKRI Future Leaders Fellowship (MR/V024965/1). M.M.S. acknowledges support from the Wellcome Trust Senior Investigator Award (098411/Z/12/Z). Work in the Knoblich laboratory is supported by the Austrian Academy of Sciences, the Austrian Science Fund (FWF) (SCORPION DOC 72-B27, Special Research Programme F7804-B and Stand-Alone grants P35680 and P35369), the Austrian Federal Ministry of Education, Science and Research, the City of Vienna, the Simons Foundation Autism Research Initiative (SFARI, no. 724430), and a European Research Council (ERC) Advanced Grant under the European Union's Horizon 2020 programs (no. 695642 and no. 874769). The authors acknowledge the use of the characterization facilities within the Harvey Flower Electron Microscopy Suite (Department of Materials) and the Facility for Imaging by Light Microscopy (FILM) at Imperial College London.
UN SDGs
This output contributes to the following UN Sustainable Development Goals (SDGs)
-
SDG 3 Good Health and Well-being
Keywords
- Humans
- Reproducibility of Results
- Organoids
- Pluripotent Stem Cells
- Brain
- stem cells
- lumenogenesis
- scaffolds
- organoids
- bioengineering
- melt electrospinning writing
Fingerprint
Dive into the research topics of 'Microfibrous Scaffolds Guide Stem Cell Lumenogenesis and Brain Organoid Engineering'. Together they form a unique fingerprint.Cite this
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver