What: 3D Cell Scaffold Generator (3D CSG) is a Grasshopper-based algorithmic toolset created by Dr Matthew Chin to generate bioinspired, 3D printable scaffolds. This toolset was developed as part of a project to create cell scaffolds recapitulating the structural complexity of tissue microenvironments.
Why: Cells interact with a wide variety of physical networks inside the human body. The connectivity of these networks has been shown to a wide range of cell behaviours. Thus, 3D cell culture platofrms, such as cell scaffolds, are typically designed to possess a network architecture that supports the migration and growth of cells. Despite this, graph theory (the mathematical study of graphs/networks) is rarely applied to drive the design of 3D cell scaffolds. To understand how the organisation of networks affects scaffold-adhered cells, we need a way to design networks that reflect the complex topologies found in microenvironments and fabricate them.
How: Note: step-by-step instructions are provided in the Grasshopper file (scaffold_AMI.gh). To design the scaffolds, we took inspiration from fibroblastic reticular cell (FRC) networks typically found in secondary lymphoid organs (e.g. lymph nodes). FRC networks are essentially the "motorways" that support the migration of immune cells (e.g. T cells and dendritic cells) and maintain normal functioning of the immune system. These networks are organised in a so-called "small-world" fashion. To generate small-world networks in 3D, we created an algorithm using Grasshopper in Rhino. The network generation is based on a random geometric graph model, previously used by Soekarjo et al. to model FRC networks in silico. We incorporated this model in our Grasshopper algorithm and added operations to improve the 3D printability of the generated structures.
Applications: Scaffolds generated by this method are intended to be fabricated by two-photon polymerisation and used as a 3D cell culture platform in tissue engineering and cell biology research.
Chin, M. H. W., Reid, B., Lachina, V., Acton, S. E. & Coppens, M.-O. Bioinspired 3D microprinted cell scaffolds: Integration of graph theory to recapitulate complex network wiring in lymph nodes. Biotechnology Journal. doi: 10.1002/biot.202300359 (Nov. 2023).
Graph analysis / computational modelling of FRC networks
- Mario Novkovic, Lucas Onder, Jovana Cupovic, Jun Abe, David Bomze, Viviana Cremasco, et al. PLoS Biol. 2016; 14(7):e1002515.
- Mario Novkovic, Lucas Onder, Gennady Bocharov and Burkhard Ludewig. Cell Reports. 2020; 30(3): 893-904.e6.
- Kasper M. W. Soekarjo, Johannes Textor, Rob J. de Boer. J Immunol. 2019; 202(11): 3318-3325.
FRC networks and immunobiology
Any suggestion to improve this toolset is welcome!
This algorithmic toolset was built using Grasshopper, a graphical algorithm editor available in the computer-aided design (CAD) application, Rhino 7.
To use some of the components in the toolset, third-party Grasshopper plug-ins will need to be installed:
| Library | Version |
|---|---|
| Anemone | 0.4 |
| Heteroptera | 0.4.9.3 |
| Fattener | 0.0.0.1 |
| WeaverBird | 0.9.0.1 |
| SpiderWeb | 0.0.4.2 |
| FlexHopper | 1.0.0.0 |
| Pufferfish | 3.0.0.0 |
| LunchBox | 2020.11.2 .0 |
| Pancake | 2.5.0.0 |
To use the the algorithm, download the scaffold_AMI.gh file and open it inside Grasshopper.
I would like to express my gratitude to the developers whose Grasshopper libraries and components have made this work possible.
I would like to thank Prof Marc-Olivier Coppens (EPSRC "Frontier Engineering" Centre for Nature Inspired Engineering, UCL) for his support and guidance on this project.
Funding: This work was supported in part by the Engineering and Physical Sciences Research Council, EPSRC, through a “Frontier Engineering: Progression” Grant (EP/S03305X/1) and an underpinning multi-user equipment grant (EP/P030084/1); NIH NCI, Cancer Research UK (CRUK) and The Mark Foundation for Cancer Research through the Cancer Grand Challenges (NexTGen).
3D Cell Scaffold Generator (3D CSG) | Copyright (c) 2023 Matthew H. W. Chin
3D CSG is free and you can redistribute and/or modify it under the terms of a GNU General Public License version 3.0 as published by the Free Software Foundation.
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