Control of Cell Behaviour Using Hierarchically Structured Functional Materials
Lead Research Organisation:
University College London
Department Name: Structural Molecular Biology
Abstract
Bioscience for Health
Abstract
Cells secrete a broad spectrum of factors in response to local environmental stimuli. This behaviour can be manipulated when cells are attached to substrates with modified surface topographical features such as grooves, ridges and pits. We hypothesize that this response could be harnessed by using nature-inspired, hierarchically structured substrates to manipulate the cell secretome. To test this, the project will combine simulation-assisted design and biological testing to screen novel cell substrates for selective cell attachment and superior activation of the secretome. The project will generate new knowledge that could be translated into applications for bioprocessing, environmental processes, and tissue engineering.
Project
Multidisciplinary research is essential to drive advances in fundamental bioscience for better health across the course of life. This includes the development of new tools that improve quality of life for the ageing population.
The overall aim of the project is to investigate whether hierarchically micro-structured substrates are capable of manipulating the cell secretome for applications in bioprocessing, environmental processes, and tissue engineering.
A range of novel hierarchically micro-structured substrates will be prepared in house using available technologies including TIPS processing and 3D printing, guided by nature-inspired designs. Prof Coppens' group specializes in nature-inspired chemical engineering (NICE), involving multi-scale theoretical, computational and experimental techniques. NICE seeks insights from fundamental physico-chemical processes behind desirable features in biology, such as scalable transport networks, adaptability and robustness, and translates these into practical applications. Applied to this project, this approach will allow for theory-assisted design and experimental synthesis to underpin the generation of the cell substrates, as well as providing new knowledge in our understanding of the fundamental mechanisms and physico-chemical phenomena that govern the production of the investigated substrates. The substrates will be evaluated through an iterative 'design-build-test-analyze' cycle. The regenerative properties of mesenchymal stem cells (MSC) are largely attributed to their secretion of bioactive trophic molecules. Since these cells are readily available and pertinent to end user needs they will be used to screen the effect of the different substrate structures on cell behaviour. Dr Day's group focuses on exploring the interaction between cells and biomaterials for tissue engineering applications. Applied to this project, this approach will allow the substrates to be analysed for quantification of cell attachment and coverage. A combination of techniques will be used for in vitro screening of the secretome. Functional activity of factors found to be elevated in the secretome will be verified using cell based assays.
Abstract
Cells secrete a broad spectrum of factors in response to local environmental stimuli. This behaviour can be manipulated when cells are attached to substrates with modified surface topographical features such as grooves, ridges and pits. We hypothesize that this response could be harnessed by using nature-inspired, hierarchically structured substrates to manipulate the cell secretome. To test this, the project will combine simulation-assisted design and biological testing to screen novel cell substrates for selective cell attachment and superior activation of the secretome. The project will generate new knowledge that could be translated into applications for bioprocessing, environmental processes, and tissue engineering.
Project
Multidisciplinary research is essential to drive advances in fundamental bioscience for better health across the course of life. This includes the development of new tools that improve quality of life for the ageing population.
The overall aim of the project is to investigate whether hierarchically micro-structured substrates are capable of manipulating the cell secretome for applications in bioprocessing, environmental processes, and tissue engineering.
A range of novel hierarchically micro-structured substrates will be prepared in house using available technologies including TIPS processing and 3D printing, guided by nature-inspired designs. Prof Coppens' group specializes in nature-inspired chemical engineering (NICE), involving multi-scale theoretical, computational and experimental techniques. NICE seeks insights from fundamental physico-chemical processes behind desirable features in biology, such as scalable transport networks, adaptability and robustness, and translates these into practical applications. Applied to this project, this approach will allow for theory-assisted design and experimental synthesis to underpin the generation of the cell substrates, as well as providing new knowledge in our understanding of the fundamental mechanisms and physico-chemical phenomena that govern the production of the investigated substrates. The substrates will be evaluated through an iterative 'design-build-test-analyze' cycle. The regenerative properties of mesenchymal stem cells (MSC) are largely attributed to their secretion of bioactive trophic molecules. Since these cells are readily available and pertinent to end user needs they will be used to screen the effect of the different substrate structures on cell behaviour. Dr Day's group focuses on exploring the interaction between cells and biomaterials for tissue engineering applications. Applied to this project, this approach will allow the substrates to be analysed for quantification of cell attachment and coverage. A combination of techniques will be used for in vitro screening of the secretome. Functional activity of factors found to be elevated in the secretome will be verified using cell based assays.
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M009513/1 | 01/10/2015 | 31/03/2024 | |||
| 1618501 | Studentship | BB/M009513/1 | 01/10/2015 | 14/11/2019 | Matthew Chin |
| Description | In the research, I have developed skills to create materials that can manipulate the behaviour of immune cells, including fabrication of materials with different mechanical properties for cell culture. Preliminary results showed that immune cells are sensitive to physical factors in the environment and that these factors can be harnessed to control them for applications such as cancer immunotherapy. I have identified limitations in my initial experimental methods and subsequently developed new approaches to address them. Through iterative rounds of optimisation, my new materials are now ready for the next cell experiment. In addition, I have explored ways to translate my ideas into something that can be used in a clinical setting. This has led to collaborations with various departments within the university such as Chemical Engineering and Biochemical Engineering. |
| Exploitation Route | My findings raise the awareness and highlight the importance of the fact that control in biology is not confined to any particular scale - for example, mechanical forces and genes are both crucial to the normal functioning of cells. Therefore, in cancer immunotherapy, researchers and clinicians should not focus on just molecular approaches, but also consider how environmental factors can be leveraged to fine tune the immune system to eliminate cancer. This can be implemented through the design of new culture protocols and biomaterials for these protocols. |
| Sectors | Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |