Realtime wireless monitoring of inflammation for improved healthcare outcomes
Lead Research Organisation:
University of Nottingham
Department Name: Sch of Pharmacy
Abstract
Millions of medical devices are surgically implanted every year, with annual sales approaching US$500 billion worldwide. Failure of implanted devices designed to be permanent can be as high as 20%, impacting patients' quality of life and burdening health services. Glucose sensors are used by most diabetics in the UK, with fine needle electrodes to sense glucose in the outermost tissue - they have recommended lifetimes of only 10-14 days because foreign body encapsulation renders them inaccurate, with each disposable unit costing £50.
The foreign body response (FBR) is the hostile immune cell reaction of the body to implants, with chronic inflammation, infection and fibrosis being the major underlying causes of implant failure. With sustained support from Wellcome Trust and EPSRC over the last fifteen years, including a current Large Grant, we are developing novel cell-instructive polymers to reduce and ultimately eliminating medical device failure.
To underpin cell-instructive polymer development, we need to be able to monitor the response of the body to novel implants in real-time. Only a snapshot of the complex biological interplay between inflammatory pathways is provided by current histological assessment of inflammatory responses measured on explants. The lack of technology to sense real-time changes of these complex processes hampers our ability to comprehensively understand these intricate inflammatory mechanisms in the hunt for polymers providing the best implant outcomes.
We propose the development of a disruptive method to achieve continuous, minimally invasive monitoring of implants in both animal models and humans. Longitudinal real-time measurements of signature inflammatory markers and FBR will be made possible using an innovative wireless bioelectronic approach: conductive nanoantennae will be decorated with antibodies to achieve continuous and minimally invasive electrical monitoring of cytokines and macrophages in a multiplexed fashion. This novel wireless monitoring method will allow us to assess new polymers in situ in real-time, aiding their successful development.
When used in humans, sensing will allow the continuous monitoring of the body's response to the new implant and therefore faster and better therapies that will ultimately improve implant success, patient outcomes and savings for healthcare providers. It will have broader application in the clinic for a variety of conditions where (device-unrelated) fibrosis is the source of morbidity and mortality.
People with diabetes suffer disproportionately from adverse implant reactions as well as chronic wounds. Through a clinical partnership with a diabetologist, we will develop an impedance sensor that does not require nanoantenna injection for earlier clinical adoption proved on glucose monitors worn by healthy volunteers.
This proposal has been co-developed by our interdisciplinary and international team, integrating expertise in cell-instructive materials, immunology, analytic devices engineering, clinical application and medical device commercialisation. The scope spans EPSRC, MRC and BBSRC remits, making it challenging for a single council and review college to fully address the multifaceted expertise and methodological range assembled to tackle this unmet need.
Benefits for the biomaterials and medical device fields include mechanistic understanding and acceleration of the novel device development process which will speed impact through MedTech products to improve options for clinicians. Immunologists will better understand the kinetics of the inflammatory response enabling more complete mechanistic descriptions. Reciprocal benefits for the rapidly advancing bioelectronics discipline will be through the clinical and pre-clinical examples it will deliver, along with the methodological experience that will be contained within the journal publications and patent filings.
The foreign body response (FBR) is the hostile immune cell reaction of the body to implants, with chronic inflammation, infection and fibrosis being the major underlying causes of implant failure. With sustained support from Wellcome Trust and EPSRC over the last fifteen years, including a current Large Grant, we are developing novel cell-instructive polymers to reduce and ultimately eliminating medical device failure.
To underpin cell-instructive polymer development, we need to be able to monitor the response of the body to novel implants in real-time. Only a snapshot of the complex biological interplay between inflammatory pathways is provided by current histological assessment of inflammatory responses measured on explants. The lack of technology to sense real-time changes of these complex processes hampers our ability to comprehensively understand these intricate inflammatory mechanisms in the hunt for polymers providing the best implant outcomes.
We propose the development of a disruptive method to achieve continuous, minimally invasive monitoring of implants in both animal models and humans. Longitudinal real-time measurements of signature inflammatory markers and FBR will be made possible using an innovative wireless bioelectronic approach: conductive nanoantennae will be decorated with antibodies to achieve continuous and minimally invasive electrical monitoring of cytokines and macrophages in a multiplexed fashion. This novel wireless monitoring method will allow us to assess new polymers in situ in real-time, aiding their successful development.
When used in humans, sensing will allow the continuous monitoring of the body's response to the new implant and therefore faster and better therapies that will ultimately improve implant success, patient outcomes and savings for healthcare providers. It will have broader application in the clinic for a variety of conditions where (device-unrelated) fibrosis is the source of morbidity and mortality.
People with diabetes suffer disproportionately from adverse implant reactions as well as chronic wounds. Through a clinical partnership with a diabetologist, we will develop an impedance sensor that does not require nanoantenna injection for earlier clinical adoption proved on glucose monitors worn by healthy volunteers.
This proposal has been co-developed by our interdisciplinary and international team, integrating expertise in cell-instructive materials, immunology, analytic devices engineering, clinical application and medical device commercialisation. The scope spans EPSRC, MRC and BBSRC remits, making it challenging for a single council and review college to fully address the multifaceted expertise and methodological range assembled to tackle this unmet need.
Benefits for the biomaterials and medical device fields include mechanistic understanding and acceleration of the novel device development process which will speed impact through MedTech products to improve options for clinicians. Immunologists will better understand the kinetics of the inflammatory response enabling more complete mechanistic descriptions. Reciprocal benefits for the rapidly advancing bioelectronics discipline will be through the clinical and pre-clinical examples it will deliver, along with the methodological experience that will be contained within the journal publications and patent filings.
