Smartwound-plasma
Lead Research Organisation:
University of Bath
Department Name: Chemistry
Abstract
This project addresses two major healthcare and societal challenges of the early 21st century: those of the rise of antimicrobial resistance (AMR) and of the growing epidemic, in developed and developing nations of chronic (non-healing) wounds.
The recent report of Lord Jim O'Neil (TACKLING DRUG-RESISTANT INFECTIONS GLOBALLY, 2016) highlights the scale of the problem we now face as micro-organisms develop resistance to antibiotic therapies that have served us extraordinarily well for now over sixty years. In his report he draws attention to a world in 2050 where AMR is a 'devastating problem' unless we find new alternative strategies to effectively destroying invading pathogens. Whilst in 2016 it was estimated that AMR gave rise to an "already large" 700,000 deaths every year, this number will increase to an "extremely disturbing" 10 million every year, which is in fact more than the number of people that currently die from cancer every year. O'Neil also makes clear, in addition to the 'tragic human costs' the economic penalty of not tackling the rise in in AMR would grow by 2050 to 'an enormous' 100 trillion USD if we do not take action.
Whilst new drug therapies will no doubt play a role in combating the rise in AMR, there is a significant role for engineering solutions. In this project plasma technology is used to generate (from ambient air) agents such as hydrogen peroxide (H2O2) that are extremely effective at killing pathogens. Because plasma delivers several agents at one time, unlike antibiotics there is no evidence to date that microbes can develop resistance to plasma.
One of major complications of chronic wounds is infection, arising from opportunistic micro-organisms. Wound infections, like any other type of infection are showing AMR. Therefore the ability to (i) detect the first signs infection and (ii) neutralise the responsible organisms immediately would provide healthcare professionals a significant new weapon.
Finally the combined technologies that will be developed can be applied to problems beyond wound infection, for example bacterial colonisation of other medical devices including urinary catheters.
The recent report of Lord Jim O'Neil (TACKLING DRUG-RESISTANT INFECTIONS GLOBALLY, 2016) highlights the scale of the problem we now face as micro-organisms develop resistance to antibiotic therapies that have served us extraordinarily well for now over sixty years. In his report he draws attention to a world in 2050 where AMR is a 'devastating problem' unless we find new alternative strategies to effectively destroying invading pathogens. Whilst in 2016 it was estimated that AMR gave rise to an "already large" 700,000 deaths every year, this number will increase to an "extremely disturbing" 10 million every year, which is in fact more than the number of people that currently die from cancer every year. O'Neil also makes clear, in addition to the 'tragic human costs' the economic penalty of not tackling the rise in in AMR would grow by 2050 to 'an enormous' 100 trillion USD if we do not take action.
Whilst new drug therapies will no doubt play a role in combating the rise in AMR, there is a significant role for engineering solutions. In this project plasma technology is used to generate (from ambient air) agents such as hydrogen peroxide (H2O2) that are extremely effective at killing pathogens. Because plasma delivers several agents at one time, unlike antibiotics there is no evidence to date that microbes can develop resistance to plasma.
One of major complications of chronic wounds is infection, arising from opportunistic micro-organisms. Wound infections, like any other type of infection are showing AMR. Therefore the ability to (i) detect the first signs infection and (ii) neutralise the responsible organisms immediately would provide healthcare professionals a significant new weapon.
Finally the combined technologies that will be developed can be applied to problems beyond wound infection, for example bacterial colonisation of other medical devices including urinary catheters.
Planned Impact
Infections are a major complication in non-healing wounds. In developed / developing countries these wounds present a growing problem of epidemic proportion. Chronic wounds which include venous leg ulcers, pressure ulcers and foot ulcers totalled 575,000 cases in 2002 at a cost to the NHS estimated at between £2.3 bn - £3.1 bn. Major underlying causes include obesity and the diabetes (over 7 million people in the UK are now pre-diabetic. Wounds being "open" are more susceptible to advantageous infection and AMR presents a significant threat.
(i) Patients with open, non-healing wounds. These are likely to be either venous leg ulcers or diabetic wounds, but hospital acquired surgical infections account for nearly 24% of all hospital acquired infections. Elderly and medically compromised (e.g. diabetics) patients can live for months, or years with open wounds. Failure of these wound to heal leads to a high probability of infection (50% of diabetic foot ulcers become infected) greatly increasing the risk of subsequent amputation. Around 20% of diabetic patients with infected foot wounds end up with some type of lower extremity amputation. In addition, minor trauma injuries can lead rapidly to diabetic foot infections for much the same reason. Burns and scolds are particularly vulnerable to infections and patients with extensive burns are most at risk.
(ii) Healthcare professionals. The increased incidence of chronic wounds presents a significant and growing burden on healthcare providers. In the case of possible infections, healthcare givers are conservative and are liable to prescribe antibiotics.
(iii) Healthcare systems. Estimates as to the cost of chronic wound management, to the NHS for example vary, but none are below £2bn pa, with agreement that this cost will grow at a rate outstripping funding. The more complicated wounds cost more to manage. This includes infected wounds. Infections are treated by antibiotics and there is evidence that there is a significant over use of antibiotics.
(iv) Manufacturers. The wound care industry is important in the UK. There is a considerable threat to manufacturers of dressing materials, as the industry rapidly moves from comparatively low technology dressings to "smart" dressings.
Beneficiaries could benefit in the following manner:
Patients. For patients with chronic wounds, technologies that provide an early signal of infection, below the critical colonisation threshold CCT, and afford immediate, effective and safe treatment offer: better wound management outcomes; potentially a reduction in the administration of antibiotics and prevent potential later (severe) complications leading to amputation. For burns patients, silver dressings are used prophylactically, but there are concerns about effectiveness and safety.
(i) Healthcare providers. New detection/treatment modalities offer healthcare professionals alternatives to prescribing antibiotics. They will benefit from a substantial reduction in the volume of patients and from reduced time per patient. Early, successful interventions will prevent more radical interventions (e.g. amputations).
(ii) Healthcare systems. We believe that the smart dressing-plasma offers a route to manage costs, whilst ensuring good patient outcomes. A clear priority is to reduce the use of antibiotics, reserving these for the "worst" indications.
(iii) Manufacturers. One of the attractive elements of the Smartwound-plasma technology is that it value adds to existing wound care materials. Smartwound-plasma technology can be built into existing hydrogel dressings, impacting little if at all on manufacturing costs, but adding (potentially) very significant value to the final product.
(i) Patients with open, non-healing wounds. These are likely to be either venous leg ulcers or diabetic wounds, but hospital acquired surgical infections account for nearly 24% of all hospital acquired infections. Elderly and medically compromised (e.g. diabetics) patients can live for months, or years with open wounds. Failure of these wound to heal leads to a high probability of infection (50% of diabetic foot ulcers become infected) greatly increasing the risk of subsequent amputation. Around 20% of diabetic patients with infected foot wounds end up with some type of lower extremity amputation. In addition, minor trauma injuries can lead rapidly to diabetic foot infections for much the same reason. Burns and scolds are particularly vulnerable to infections and patients with extensive burns are most at risk.
(ii) Healthcare professionals. The increased incidence of chronic wounds presents a significant and growing burden on healthcare providers. In the case of possible infections, healthcare givers are conservative and are liable to prescribe antibiotics.
(iii) Healthcare systems. Estimates as to the cost of chronic wound management, to the NHS for example vary, but none are below £2bn pa, with agreement that this cost will grow at a rate outstripping funding. The more complicated wounds cost more to manage. This includes infected wounds. Infections are treated by antibiotics and there is evidence that there is a significant over use of antibiotics.
(iv) Manufacturers. The wound care industry is important in the UK. There is a considerable threat to manufacturers of dressing materials, as the industry rapidly moves from comparatively low technology dressings to "smart" dressings.
Beneficiaries could benefit in the following manner:
Patients. For patients with chronic wounds, technologies that provide an early signal of infection, below the critical colonisation threshold CCT, and afford immediate, effective and safe treatment offer: better wound management outcomes; potentially a reduction in the administration of antibiotics and prevent potential later (severe) complications leading to amputation. For burns patients, silver dressings are used prophylactically, but there are concerns about effectiveness and safety.
(i) Healthcare providers. New detection/treatment modalities offer healthcare professionals alternatives to prescribing antibiotics. They will benefit from a substantial reduction in the volume of patients and from reduced time per patient. Early, successful interventions will prevent more radical interventions (e.g. amputations).
(ii) Healthcare systems. We believe that the smart dressing-plasma offers a route to manage costs, whilst ensuring good patient outcomes. A clear priority is to reduce the use of antibiotics, reserving these for the "worst" indications.
(iii) Manufacturers. One of the attractive elements of the Smartwound-plasma technology is that it value adds to existing wound care materials. Smartwound-plasma technology can be built into existing hydrogel dressings, impacting little if at all on manufacturing costs, but adding (potentially) very significant value to the final product.
Publications
Xu S
(2019)
A boronic acid-based fluorescent hydrogel for monosaccharide detection
in Frontiers of Chemical Science and Engineering
Sedgwick AC
(2018)
An ESIPT Probe for the Ratiometric Imaging of Peroxynitrite Facilitated by Binding to Aß-Aggregates.
in Journal of the American Chemical Society
Patenall BL
(2021)
Assessment of mutations induced by cold atmospheric plasma jet treatment relative to known mutagens in Escherichia coli.
in Mutagenesis
Williams G
(2020)
Boronate ester cross-linked PVA hydrogels for the capture and H 2 O 2 -mediated release of active fluorophores
in Chemical Communications
Gaur N
(2023)
Cold Atmospheric Plasma-Activated Composite Hydrogel for an Enhanced and On-Demand Delivery of Antimicrobials.
in ACS applied materials & interfaces
Davies A
(2020)
Consensus demonstrates four indicators needed to standardize burn wound infection reporting across trials in a single-country study (ICon-B study)
in Journal of Hospital Infection
Hathaway H
(2019)
Delivery and quantification of hydrogen peroxide generated via cold atmospheric pressure plasma through biological material
in Journal of Physics D: Applied Physics
Lampard EV
(2018)
Dye Displacement Assay for Saccharides using Benzoxaborole Hydrogels.
in ChemistryOpen
Ghimire B
(2021)
Enhancement of hydrogen peroxide production from an atmospheric pressure argon plasma jet and implications to the antibacterial activity of plasma activated water
in Plasma Sources Science and Technology
Patenall BL
(2023)
Evidence of bacterial biofilms within acute wounds: a systematic review.
in Journal of wound care
Patenall B
(2018)
Limiting Pseudomonas aeruginosa Biofilm Formation Using Cold Atmospheric Pressure Plasma
in Plasma Medicine
Gwynne L
(2019)
Long Wavelength TCF-Based Fluorescent Probe for the Detection of Alkaline Phosphatase in Live Cells.
in Frontiers in chemistry
Sedgwick AC
(2018)
Long-wavelength TCF-based fluorescence probes for the detection and intracellular imaging of biological thiols.
in Chemical communications (Cambridge, England)
Szili E
(2021)
On-demand cold plasma activation of acetyl donors for bacteria and virus decontamination
in Applied Physics Letters
Davies A
(2019)
Protocol for the development of a core indicator set for reporting burn wound infection in trials: ICon-B study.
in BMJ open
Patenall BL
(2019)
Reaction-based indicator displacement assay (RIA) for the development of a triggered release system capable of biofilm inhibition.
in Chemical communications (Cambridge, England)
Thet NT
(2020)
SPaCE Swab: Point-of-Care Sensor for Simple and Rapid Detection of Acute Wound Infection.
in ACS sensors
Yan KC
(2022)
TCF-based fluorescent probe for monitoring superoxide anion produced in bacteria under chloramphenicol- and heat-induced stress.
in Chemical communications (Cambridge, England)
Ghimire B
(2021)
The influence of a second ground electrode on hydrogen peroxide production from an atmospheric pressure argon plasma jet and correlation to antibacterial efficacy and mammalian cell cytotoxicity
in Journal of Physics D: Applied Physics
Description | The team showed that using a cold atmospheric plasma jet on a bacterial biofilm (a model of wound infection) could produce hydrogen peroxide which has been proposed as a method of clearing such biofilms from wounds. We found that the biofilm interacted with the het and reduce the effective concentration of the hydrogen peroxide and therefore the potential utility of using plasma to control wound infection. This has very important implication since plasma jets are being proposed for wound cleaning in the clinic, with several commercial companies producing jet. Furthermore, we found that direct plasma had the potential to cause mutations of bacteria in the biofilm, which might accelerate evolution of antimicrobial resistance in wound bacteria. Our solution to these problems was to create a hydrogel sheet impregnated with iodine-poviodine, which is an antiseptic currently used in wound care. Application of the plasma jet appeared to release an active form of the antiseptic and improve its ability to control biofilms in wound models. Prototypes have been developed which are being taken forward in a follow up research programme. |
Exploitation Route | IP is being protected and technology will be tested on model biofilms created by direct swabbing of patients with diabetic foot ulcers in a follow up project. |
Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
Description | Findings from this grant are underpinning the development of our two infection swab sensor concepts, for wounds and for neonatal babies: SPaCE Wound infection sensor: https://smartwound.co.uk/the-space-sensor SPaCE-GBS neonatal infection sensor: https://smartwound.co.uk/gbs Research is being taken forward in a follow up research programme: Plasma-activated antimicrobial hydrogel therapy (PAHT) for combating infections in diabetic foot ulcers EP/V00462X/1 |
First Year Of Impact | 2020 |
Sector | Healthcare |
Impact Types | Societal |
Description | Development of an infection detecting wound dressing Competition: Precision medicine technologies: shaping the future |
Amount | £24,883 (GBP) |
Organisation | University of Bath |
Sector | Academic/University |
Country | United Kingdom |
Start | 11/2018 |
End | 10/2019 |
Description | Plasma-activated antimicrobial hydrogel therapy (PAHT) for combating infections in diabetic foot ulcers |
Amount | £407,563 (GBP) |
Funding ID | EP/V00462X/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 02/2021 |
End | 10/2024 |
Description | Smartwound-development |
Amount | £74,540 (GBP) |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 04/2018 |
End | 03/2019 |
Description | Urology Foundation small grant scheme |
Amount | £9,401 (GBP) |
Organisation | University of Bath |
Sector | Academic/University |
Country | United Kingdom |
Start | 01/2019 |
End | 08/2019 |
Title | Composition |
Description | Field of Invention The present invention relates to composite hydrogels comprising 5 at least one active pharmaceutical ingredient that can be selectively released from the hydrogel for delivery to a patient. Summary of the Invention According to a first aspect of the invention, there is provided a composite hydrogel comprising an anionic or cationic functional group-containing polymer and at least one active pharmaceutical agent (API), wherein the API is oppositely charged to the anionic or cationic functional group-containing polymer. One challenge in designing hydrogels for delivery of APIs to skin, wounds or other topical areas is to trigger drug release following a specific stimulus. It is undesirable to have slow passive release from a hydrogel dressing if the drug being eluted is present in concentrations below its therapeutic limit. The composite hydrogel described herein allows at least one API to be delivered to skin, wounds or other topical areas under specific conditions in a dose-controllable and reproducible manner. A second aspect of the invention provides a method of displacing an active pharmaceutical ingredient from a composite hydrogel according to the first aspect of the invention, the method comprising a step of treating the composite hydrogel with an ion source. A third aspect of the invention provides a wound dressing comprising the composite hydrogel of the first aspect of the invention. A fourth aspect of the invention provides a method of treating a wound comprising the steps of: (a) applying the wound dressing of the third aspect of the invention or the composite hydrogel of the first aspect of the invention to a wound, and (b) displacing the at least one active pharmaceutical ingredient by the method described in the second aspect of the invention. A fifth aspect of the invention provides a method of delivering an API to a patient comprising the steps of: (a) applying the composite hydrogel of the first aspect of the invention to a patient, and (b) displacing the at least one active pharmaceutical ingredient by the method described in the second aspect of the invention. |
IP Reference | |
Protection | Patent / Patent application |
Year Protection Granted | 2022 |
Licensed | No |
Impact | Plan to licence to Plasma-4 Ltd in next 6 months |
Company Name | PLASMA4 LIMITED |
Description | Plasma4 is a micro SME founded to develop the technology discovered in the grant towards clinical use. Professor Rob Short (CI) at Lancaster is the founder and director. |
Year Established | 2021 |
Impact | None - yet, it is only 4 months old. |
Description | Combe Down Primary school science week hands on activity: polymers and gels |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | As part f Combe Down Primary Schools annual 'Science Week', I ran an interactive workshop for 5 - 6 year old children on gels and polymers. Chiilden investigated sodium polyacrylate gels, swelling in water and deswelling with salts. |
Year(s) Of Engagement Activity | 2018 |
Description | Online talk at POLY-CHAR 2022 international conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Conference talk at POLY-CHAR 2022 on the composite hydrogel system developed at Bath |
Year(s) Of Engagement Activity | 2022 |
URL | https://poly-char2022.org/ |
Description | Royal United Hospital research showcase event |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | I demonstrated our infection diagnostic technology and plans for future RUH-Bath collaboration at the 1st University of Bath / RUH reearxh networking event. |
Year(s) Of Engagement Activity | 2019 |
Description | Talk to Corona Club (club for elderly ladies) on paediatric burns |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Talk to Cornona Club on the problem of Paediatric Burns and our approaches to better diagnosis and treatment. |
Year(s) Of Engagement Activity | 2019 |