Micro-patterned polymer substrates as novel models of epidermal wound healing
Lead Research Organisation:
Queen Mary University of London
Department Name: Blizard Institute of Cell and Molecular
Abstract
The proposed research will develop a novel in vitro model of wound healing within the skin. We will employ state-of-the-art micro-fabrication techniques to create engineered substrates for culturing human keratinocytes. This technology will allow us to precisely control multiple parameters of the wound environment. Specifically, we will determine how the composition, geometry, and stiffness of the wound influence cell behaviour. In addition, we will examine the molecular signalling pathways that regulate the cellular responses to these different environments. This project has the potential to provide significant insights into how human skin cells sense and respond to extrinsic signals during the wound healing process. Moreover, this model system may be a powerful tool for future cell biology studies, drug screening, and other types of translational research.
Technical Summary
The overall objective of the proposed research is to determine how human keratinocytes sense and respond to changes in their environment during wound healing. Micro-contact printing techniques will be used to create a novel in vitro model of epidermal wound healing. Micro-patterned substrates will consist of islands of protein resistant polymer brushes, which will serve as model 'wound beds', and will be surrounded by confluent human keratinocytes. Migration into the wound will be activated by coupling specific extracellular matrix proteins to the polymer brushes. This system will allow us to precisely control the size, shape, and composition of the wound bed. In addition, this assay will be used to investigate the role of serum response factor (SRF) signalling in keratinocyte mechano-sensing during the wound healing process. This work will be carried out in three specific aims and test two major hypotheses: (1) The composition and structure of the wound bed regulates re-epithelialization via altered migration and proliferation of the keratinocytes. (2) SRF mediates cellular responses to physical cues during epidermal wound healing.
Planned Impact
The main objective of the project is to improve our fundamental understanding of the normal wound healing process through the use of a novel in vitro system. While the immediate benefits of this knowledge will be to related academic communities, the model system may have long-term benefits to the UK economy and to public health and well-being. Our model of wound healing may be a useful assay for screening new compounds or bio-active molecules for treating chronic ulcers or skin diseases. As a tool for pharmaceutical companies, this model could benefit the UK and world economy. More importantly, the assay could aid the drug development process and lead to improved treatments for patients and overall public health. The knowledge generated by the proposed studies may also provide important information for wound management and tissue repair. Our studies will establish the basic role of physical cues in the normal wound healing process. This information may be useful to those in the tissue engineering field and provide design criteria for biomaterials and tissue scaffolds. Understanding the physical regulation of wound healing may also be important for healthcare professionals when applying wound dressings and sutures. Therefore, this project could benefit the economy by guiding the development of new tissue engineering and regenerative medicine products. Patients would also benefit from more effective products and treatments. Beyond the pharmaceutical and healthcare industries, this project may stimulate the materials and chemical industries. By providing a new application for micro-contact printing and polymer brushes, this project may lead to the development of new materials, chemicals, or processes that are more ideally suited for these types of experimental systems.
People |
ORCID iD |
John Connelly (Principal Investigator) |
Publications
Almeida FV
(2019)
High-Content Analysis of Cell Migration Dynamics within a Micropatterned Screening Platform.
in Advanced biosystems
Almeida FV
(2015)
The cytolinker plectin regulates nuclear mechanotransduction in keratinocytes.
in Journal of cell science
Costa P
(2012)
Biophysical signals controlling cell fate decisions: how do stem cells really feel?
in The international journal of biochemistry & cell biology
Costa P
(2021)
Regulation of collective cell polarity and migration using dynamically adhesive micropatterned substrates.
in Acta biomaterialia
Costa P
(2014)
Directing cell migration using micropatterned and dynamically adhesive polymer brushes.
in Acta biomaterialia
Sharili AS
(2016)
Nuclear actin modulates cell motility via transcriptional regulation of adhesive and cytoskeletal genes.
in Scientific reports
Theocharidis G
(2016)
Type VI Collagen Regulates Dermal Matrix Assembly and Fibroblast Motility.
in The Journal of investigative dermatology
Description | We have successfully developed a novel cell migration assay using micro-fabrication technologies. This platform has allowed us to control and study how interactions between cells and their environment regulate collective migration, a fundamental processes involved in wound repair. We are currently investigating how these extracellular cues impact cell polarity (i.e. directionality) and fate. In addition, further research to scale up this platform for high-content screening has uncovered novel epigenetic regulatory mechanisms controlling keratinocyte migration. These findings have important implications for wound healing and may represent new therapeutic targets for improving impaired healing. |
Exploitation Route | The technology developed during this project could be used in several different ways. First, it will likely lead to new knowledge and understanding of basic biological processes. Second, as a biotechnology tool it could be a valuable resource for drug testing and development. Finally, the specific findings of our studies could be used to guide the development of scaffolds for tissue engineering and wound repair. |
Sectors | Education Healthcare Pharmaceuticals and Medical Biotechnology |
Description | Through this research grant we have developed a novel, micro-patterned assay for studying cell migration. This work has led to several key outputs, including knowledge dissemination through primary research articles and conference presentations, and securing further grant funding to develop this technology into a high-throughout format. In addition, this project has fostered public engagement activities through the development of an on-line learning resources about wound healing and tissue engineering. |
First Year Of Impact | 2012 |
Sector | Digital/Communication/Information Technologies (including Software),Education |
Impact Types | Societal Economic |
Description | Honor Fell Travel Award |
Amount | £1,000 (GBP) |
Organisation | Company of Biologists |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 05/2012 |
End | 07/2012 |
Description | Queen Mary Innovation Award |
Amount | £10,000 (GBP) |
Organisation | Queen Mary University of London |
Sector | Academic/University |
Country | United Kingdom |
Start | 01/2014 |
End | 09/2014 |
Description | Research Project Grant |
Amount | £117,823 (GBP) |
Organisation | Dr Hadwen Trust (DHT) |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2015 |
End | 12/2016 |
Title | Development of micro-patterned migration assay |
Description | We have successfully developed a novel cell migration assay that allows us to precisely control migration over space and time. This technique involves micro-contact printing and a light activated coupling reaction to create dynamically adhesive surfaces. |
Type Of Material | Technology assay or reagent |
Year Produced | 2013 |
Provided To Others? | Yes |
Impact | We are in the process of developing a new research collaboration with Dr. Simona Parinello at Imperial College, and this assay will be used in a recently awarded grant from the Dr. Hadwen Trust. |
Description | Development of virtual experiment educational tool |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Schools |
Results and Impact | Through the Centre of the Cell and the X-plore Health initiative, we developed an on-line virtual experiment called 'Engineer Skin'. The aim was to teach secondary school children about the concepts of tissue engineering and how it could specifically be applied to skin repair. None aware of yet. |
Year(s) Of Engagement Activity | 2012 |
URL | http://www.xplorehealth.eu/en/media/engineer-skin |
Description | Invited seminar at Imperial College London |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Dr. Connelly gave an invited seminar to the Bioengineering Department at Imperial College London. Approximately 60 academics and students attended the talk, and it resulted in discussion and questions afterwards. |
Year(s) Of Engagement Activity | 2015 |
Description | Invited seminar at King's College London |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | The talk led to valuable discussion and plans for future studies and potential collaborations. None known yet |
Year(s) Of Engagement Activity | 2014 |
Description | Invited seminar at Trinity College Dublin |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | I presented our previous and on-going research on micro-patterned models of wound healing to the Bioengineering Department at Trinity College Dublin. The seminar resulted in questions and discussion about the research and the development of new professional contacts in Ireland. |
Year(s) Of Engagement Activity | 2016 |
Description | Invited seminar at University of Liverpool |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | The talk resulted in discussion with lecturers and students about significance of the findings, future work, and potential collaborations Scientists in Liverpool planned new studies and approaches based on our discussion |
Year(s) Of Engagement Activity | 2013 |
Description | Invited seminar at University of Pennsylvania |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Participants in your research or patient groups |
Results and Impact | We presented our findings in a seminar to the dermatology and orthopaedic departments within the School of Medicine at the University of Pennsylvania. no actual impacts realised to date |
Year(s) Of Engagement Activity | 2012 |
Description | Invited seminar at University of Southampton |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | We presented the micro-patterned model at an invited seminar at the University of Southampton on November 9th, 2012. The audience consisted of researchers and academics in the Engineering Department and School of Medicine. no actual impacts realised to date |
Year(s) Of Engagement Activity | 2012 |
Description | Pint of Science |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | 30 members of the public attended an evening lecture in which I discussed how micro-fabrication technologies are currently being used in biomedical research for creating model 'organs on a chip'. The lecture was followed by a question and answer and discussion session with the audience. |
Year(s) Of Engagement Activity | 2016 |