Non-tissue staining photodynamically-active fibres for antibiotic-free infection control in chronic wounds
Lead Research Organisation:
University of Leeds
Department Name: Mechanical Engineering
Abstract
This project now aims to integrate this system with safe photosensitiser (PS) dye to achieve on-demand photoinduced antimicrobial activity and minimised reliance on antibiotics. The PhD candidate will develop methods and fibrous configurations aiming to accomplish antimicrobial effect, yet ensuring retention of the photosensitiser dye in the fibres even in physiological conditions. This is key to enable long-lasting antimicrobial effect and to minimise tissue staining following application of the device to the wound.
We have already investigated demonstrated incorporation of the PS dye into fibres to achieve antimicrobial photodynamic therapy (aPDT) effect when irradiated with a suitable light source. In collaboration with Neotherix Ltd. and the University of Massachusetts Amherst (USA), we have also confirmed and quantified the encapsulation of resulting fibrous meshes with the PS dye via manufacturing processes established at Leeds and demonstrated aPDT effect against Escherichia coli as exemplary chronic wound pathogen.
Aiming to achieve long-lasting antimicrobial aPDT effect, we now want to investigate and control the mechanism with which the PS dye is incorporated in the fibres. Typical PS dyes are soluble in aqueous environment. Consequently, if simply dispersed in the fibres, diffusion of the PS dye away of the fibres can be expected over time following fibre contact with the wound, resulting in tissue staining and short-lived antimicrobial capability.
Aim: to develop industry-compliant fibre spinning approaches yielding (i) fibrous configurations with controlled PS dye loading and release capability; (ii) rapid (< 3 min) broad-spectrum aPDT effect following fibre exposure to a specific light source, e.g. via employment of a smartphone light emitting device. Depending on progress, investigation of the prototype with human patient-derived wound exudate can also be carried out.
We have already investigated demonstrated incorporation of the PS dye into fibres to achieve antimicrobial photodynamic therapy (aPDT) effect when irradiated with a suitable light source. In collaboration with Neotherix Ltd. and the University of Massachusetts Amherst (USA), we have also confirmed and quantified the encapsulation of resulting fibrous meshes with the PS dye via manufacturing processes established at Leeds and demonstrated aPDT effect against Escherichia coli as exemplary chronic wound pathogen.
Aiming to achieve long-lasting antimicrobial aPDT effect, we now want to investigate and control the mechanism with which the PS dye is incorporated in the fibres. Typical PS dyes are soluble in aqueous environment. Consequently, if simply dispersed in the fibres, diffusion of the PS dye away of the fibres can be expected over time following fibre contact with the wound, resulting in tissue staining and short-lived antimicrobial capability.
Aim: to develop industry-compliant fibre spinning approaches yielding (i) fibrous configurations with controlled PS dye loading and release capability; (ii) rapid (< 3 min) broad-spectrum aPDT effect following fibre exposure to a specific light source, e.g. via employment of a smartphone light emitting device. Depending on progress, investigation of the prototype with human patient-derived wound exudate can also be carried out.
Planned Impact
Regenerative Medicine been defined as "an interdisciplinary approach, spanning tissue
engineering, stem cell biology, gene therapy, cellular therapeutics, biomaterials (scaffolds and matrices),nanoscience, bioengineering and chemical biology that seeks to repair or replace damaged or diseased human cells or tissues to restore normal function, (UK Strategy for Regenerative Medicine). CDT TERM will focus on acellular therapies, scaffolds,autologous cells and regenerative devices, which can be delivered to patients as class three device interventions, thus reducing the time and cost of translation and which provide an opportunity to deliver economic growth and benefits to health in the next decade. The primary beneficiaries of CDT TERM are patients, the health service, UK industry, as well as the academic community and the students themselves. Recognising that the impact and benefit from CDT TERM will arise in the future, the statements describing impact below are supported by evidence of actual impact from our existing research and training.
Patients will benefit from regenerative interventions, which address unmet clinical needs, have improved safety and reliability, have been stratified to meet patients needs and manufactured in a cost effective manner. An example of impact arising from previous students work is a new acellular scaffold for young adult heart valve repair, which has demonstrated improved clinical outcomes at five years.
The Health Service will benefit from collaborations on research, development and evaluation of technologies, through existing partnerships with National Health Service Blood and Transplant NHSBT and the Leeds Biomedical Musculoskeletal Research Unit LMBRU. NHSBT will benefit through collaborative projects, through technology transfer, through enhancement of manufacturing processes, through pre-clinical evaluation of products and supply of trained personnel. We currently collaborate on heart valves, skin, ligaments and arteries, have licensed patents on acellular bioprocesses, and support product and process developments with pre-clinical testing and simulation. LMBRU and NHS clinicians will benefits from our collaborative research and training environment and access to our research expertise, facilities and students. Existing collaborative projects include, delivery devices for minimally manipulated stem cells and applied imaging for early OA.
Industry will benefit from supply of highly trained multidisciplinary engineers and scientists, from collaborative research and development projects, from creation and translation of IP, creation of spinout companies and through access to unique equipment, facilities and expertise. We have demonstrated: successful spin outs in form of Tissue Regenix and Credentis; successful commercialisation of a novel biological scaffolds for vascular patch repair; sustainable long term R and D and successful licensing of technology with DePuy; collaborative research with Invibio, partnering with Simulation Solutions to develop new pre-clinical simulation systems, which been adopted by regulatory agencies such as China FDA. Our graduates and researchers are employed by our industry partners.
The academic community will benefit through collaborative research and access to our facilities. We have funded collaborations with over 30 academic institutions in UK and internationally. The CDT TERM will support these collaborations and the academic partners will support student research and training. The CDT students will benefit from enhanced integrated multidisciplinary training and research, a cohort experience focused on research innovation and translation, access to our research partners, industry and clinicians. Feedback from existing students has identified the benefit of the multidisciplinary experience, the depth and breadth of excellence in our research base, the outstanding facilities and the added value of the cohort training.
engineering, stem cell biology, gene therapy, cellular therapeutics, biomaterials (scaffolds and matrices),nanoscience, bioengineering and chemical biology that seeks to repair or replace damaged or diseased human cells or tissues to restore normal function, (UK Strategy for Regenerative Medicine). CDT TERM will focus on acellular therapies, scaffolds,autologous cells and regenerative devices, which can be delivered to patients as class three device interventions, thus reducing the time and cost of translation and which provide an opportunity to deliver economic growth and benefits to health in the next decade. The primary beneficiaries of CDT TERM are patients, the health service, UK industry, as well as the academic community and the students themselves. Recognising that the impact and benefit from CDT TERM will arise in the future, the statements describing impact below are supported by evidence of actual impact from our existing research and training.
Patients will benefit from regenerative interventions, which address unmet clinical needs, have improved safety and reliability, have been stratified to meet patients needs and manufactured in a cost effective manner. An example of impact arising from previous students work is a new acellular scaffold for young adult heart valve repair, which has demonstrated improved clinical outcomes at five years.
The Health Service will benefit from collaborations on research, development and evaluation of technologies, through existing partnerships with National Health Service Blood and Transplant NHSBT and the Leeds Biomedical Musculoskeletal Research Unit LMBRU. NHSBT will benefit through collaborative projects, through technology transfer, through enhancement of manufacturing processes, through pre-clinical evaluation of products and supply of trained personnel. We currently collaborate on heart valves, skin, ligaments and arteries, have licensed patents on acellular bioprocesses, and support product and process developments with pre-clinical testing and simulation. LMBRU and NHS clinicians will benefits from our collaborative research and training environment and access to our research expertise, facilities and students. Existing collaborative projects include, delivery devices for minimally manipulated stem cells and applied imaging for early OA.
Industry will benefit from supply of highly trained multidisciplinary engineers and scientists, from collaborative research and development projects, from creation and translation of IP, creation of spinout companies and through access to unique equipment, facilities and expertise. We have demonstrated: successful spin outs in form of Tissue Regenix and Credentis; successful commercialisation of a novel biological scaffolds for vascular patch repair; sustainable long term R and D and successful licensing of technology with DePuy; collaborative research with Invibio, partnering with Simulation Solutions to develop new pre-clinical simulation systems, which been adopted by regulatory agencies such as China FDA. Our graduates and researchers are employed by our industry partners.
The academic community will benefit through collaborative research and access to our facilities. We have funded collaborations with over 30 academic institutions in UK and internationally. The CDT TERM will support these collaborations and the academic partners will support student research and training. The CDT students will benefit from enhanced integrated multidisciplinary training and research, a cohort experience focused on research innovation and translation, access to our research partners, industry and clinicians. Feedback from existing students has identified the benefit of the multidisciplinary experience, the depth and breadth of excellence in our research base, the outstanding facilities and the added value of the cohort training.
Organisations
People |
ORCID iD |
| Giuseppe Tronci (Primary Supervisor) | |
| Emily Absalom (Student) |