Bubbles to Bond Broken Bones: targeted drug delivery for fracture repair
Lead Research Organisation:
University of Southampton
Department Name: Human Development and Health
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Publications
Ferri S
(2021)
Tailoring the size of ultrasound responsive lipid-shelled nanodroplets by varying production parameters and environmental conditions.
in Ultrasonics sonochemistry
Polydorou A
(2023)
An investigation into the cytotoxic effects of microbubbles and their constituents on osteosarcoma and bone marrow stromal cells
in Biochimica et Biophysica Acta (BBA) - General Subjects
Wu Q
(2021)
Investigation of the Acoustic Vaporization Threshold of Lipid-Coated Perfluorobutane Nanodroplets Using Both High-Speed Optical Imaging and Acoustic Methods.
in Ultrasound in medicine & biology
| Description | We have successfully formulated a drug-carrying nanodroplet that vaporises and releases the drug when stimulated by ultrasound. We are now investigating the effect of this on human cells and tissues, and will soon perform animal experiments to see if we can heal bones. this has led to 3 publications so far. We have successfully develop an in vivo ultrasound device for stimulation UCSA in bone fractures. This allows is to manipulate ultrasound contrast agents as they flow through a bone fracture and cause them to release drugs and stimulate the bone to heal. We are now measuring this in mice. We have developed a project to measure ultrasound contrast agents in bone fracture. This has been successful indicating that contrast agents may be manipulated in humans, as well as in cells and mice. We have as a result of this award led a human trial to test the hypothesis that microbubble contrast agents can be imaged in bone fracture. This is currently underway with 9 patients treated so far with 1 further to do. This will be published soon |
| Exploitation Route | Data published and in public domain for others to learn. |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
| Description | The findings from this exciting intervention have been positive, with some encouraging results enabling us to continue to pursue our research in both patients. students and with industrial partners. The key scientific findings arising from this project include: (1) ultrasound-responsive emulsions can be modified to include osteogenic agents, which release their payload on ultrasound stimulation; (2) novel formulations of both microbubbles and nanodroplets are biocompatible in primary cells isolated from human patients and can induce their differentiation; (3) ultrasound responsive agents can be stimulated to transfer energy in mouse bone fractures and (4) in a human clinical study initiated as a direct result of this EPSRC funded research, we have found that microbubbles perfuse extensively human acute bone fracture. This data paved the way directly for a clinical that is underway presently on 10 patient volunteers, 9 of which have been treated to date (March 2023). It has also led to the implementation of a new clinical trial on a larger cohort of patients and further development of the technology in preclinical models through MRC funding (this is due to start in May 2023). It has paved the way directly for a renewed partnership with GE Healthcare, the major manufacturer of clinical ultrasound devices in NHS trusts in the UK, with inward investment through industrial and NHS partnership of £200000. It has led to academic publications to date as well preliminary work on filing a UK patent, after which the main body of results will be published academically. Further to this, the work informed a yearly residential workshop, which has run throughout covid lockdowns remotely. This course has had a direct impact on young people choosing to pursue engineering related disciplines. In partnership with educational charity The Smallpeice Trust, 142 students aged 15 to 16 completed workshops; 91.6% of males and 85.3% of females agreed with the statement: 'This course has increased your interest in engineering generally', and 48.3% of males and 54.9% of females agreed with the statement: 'This course has persuaded you to follow a career in this field of engineering.' Of those students who selected science or engineering degrees at university and participated in the Southampton course 84.8% (28/33) said the course had 'increased interest in the subject' and 26.8% (9/34) said the course directly 'influenced their degree choice'. |
| First Year Of Impact | 2020 |
| Sector | Education,Healthcare,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Societal,Economic |
| Description | Nanoemulsions for oxygen delivery in bone repair |
| Amount | £75,000 (GBP) |
| Funding ID | 081 |
| Organisation | Orthopaedic Research UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 02/2021 |
| End | 02/2025 |
| Description | Ultrasound-responsive agents for non-invasive fracture healing |
| Amount | £1,200,000 (GBP) |
| Funding ID | MR/X009793/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 05/2023 |
| End | 04/2026 |
| Description | Ultrasound-responsive agents for non-invasive fracture healing |
| Amount | £50,000 (GBP) |
| Organisation | Orthopaedic Research UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 09/2022 |
| End | 08/2023 |
| Description | Dstl partnership |
| Organisation | Defence Science & Technology Laboratory (DSTL) |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | This partnership has developed to exploit mutual interests in drug delivery in infection that have arisen from successful preliminary data from our ESPRC funder project. This involves development of ultrasound activated agents for delivery of antibiotics or inhibition of infection |
| Collaborator Contribution | Our institution and Dstl has contributed funding to a PhD student to explore research aligned with this objective. This has also been supported by a further 2 part time students working between our insitutes (one at Dstl and one at UoS). |
| Impact | Funding from Dstl to UoS and vice versa of £140,000 GBP |
| Start Year | 2021 |
| Description | GE Healthcare |
| Organisation | GE Healthcare Limited |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We initiated this partnership to translate the work to the clinic. This has led to involvement of technical specialists and further inward in kind investment of £80,000 |
| Collaborator Contribution | Technical guidance with instrumentation and formulations |
| Impact | Presentations at national and international conferences. |
| Start Year | 2020 |
| Title | Contrast-enhanced ultrasound imaging of displaced humeral fractures: pragmatic single-centre study. |
| Description | This trial was to determine if a commercial formulation of microbubbles, SonoVue, could be imaged in human bone fractures. It is a trial of 10 patients with 9 recruited to date. This was funded by an ESPRC IAA that we were awarded based on work done in this study. |
| Type | Therapeutic Intervention - Medical Devices |
| Current Stage Of Development | Early clinical assessment |
| Year Development Stage Completed | 2023 |
| Development Status | Under active development/distribution |
| Impact | Impacts on awareness of contrast enhanced imaging in orthopaedic surgeons and radiologists |