Bubbles for bone: acoustic stimulation for drug delivery in fracture repair.
Lead Research Organisation:
University of Southampton
Department Name: Human Development and Health
Abstract
Priority Alignment: Interdisciplinary
Bone fractures and their associated complications are a major societal problem that is set to get significantly worse as our population ages. Delayed bone healing and extended rehabilitation contribute to the 39 billion Euros per year cost of bone injuries to the European economy, and approximately 150,000 wrist, vertebral and hip fractures cost the UK £2.1 billion annually. A proportion of bone fractures fail to heal appropriately with current clinical interventions, which include mechanical fixation or, more rarely, biomaterials and/or bioactive agents. New therapies are therefore urgently required. As yet, there is no clinically approved, systemic therapy for bone fracture.
We are developing such an approach. In preliminary work, we have found that nanoparticles (NPs) of known size accumulate at injury sites during specific windows post-fracture. We have used this approach to deliver therapeutic molecules to the injury site selectively at different phases of fracture healing without disrupting the healing tissue, the integrity of which is often critical to satisfactory outcomes. Aside from enabling the passive release of drugs at fracture sites, these observations now provide the exciting opportunity to remotely and actively control drug release and tissue stimulation in bone repair.
In this studentship, we propose to attempt this by delivering ultrasound-responsive bubbles to the fracture site. Ultrasound stimulation of bubbles causes them to resonate. In our preliminary data, we have shown that this results in the release of bubble-associated drugs, improved uptake of compounds in nearby cells, and mechanostimulation of cells through either direct membrane interaction or via shear of extracellular media. More recently we have found that acoustically-responsive bubbles can be fabricated in the nanometre size range and that they accumulate at fracture sites. This means we will be able to localise drug-containing nanobubbles at bone fracture sites, before remotely stimulating them with ultrasound to both release their cargo and mechanostimulate the surrounding tissue.
In this studentship, the student will first develop and optimise nanobubbles and ultrasound-responsive nanodroplet formulations (which cavitate to form microbubbles upon ultrasound stimulation) to demonstrate that these agents can simultaneously be used to deliver drugs and to mechanostimulate stem cells, inducing their differentiation in in vitro models. The student will then determine which size and chemical characteristics lead to localisation of bubbles to the fracture callus post-injury. Finally, the student will test in vivo whether acoustic stimulation of fracture callus-localised bubbles affects the rate and quality of bone fracture healing. The student will train with experts in stem cell biology, mechanobiology, nanotechnology and ultrasonics from established experts at University of Southampton
Bone fractures and their associated complications are a major societal problem that is set to get significantly worse as our population ages. Delayed bone healing and extended rehabilitation contribute to the 39 billion Euros per year cost of bone injuries to the European economy, and approximately 150,000 wrist, vertebral and hip fractures cost the UK £2.1 billion annually. A proportion of bone fractures fail to heal appropriately with current clinical interventions, which include mechanical fixation or, more rarely, biomaterials and/or bioactive agents. New therapies are therefore urgently required. As yet, there is no clinically approved, systemic therapy for bone fracture.
We are developing such an approach. In preliminary work, we have found that nanoparticles (NPs) of known size accumulate at injury sites during specific windows post-fracture. We have used this approach to deliver therapeutic molecules to the injury site selectively at different phases of fracture healing without disrupting the healing tissue, the integrity of which is often critical to satisfactory outcomes. Aside from enabling the passive release of drugs at fracture sites, these observations now provide the exciting opportunity to remotely and actively control drug release and tissue stimulation in bone repair.
In this studentship, we propose to attempt this by delivering ultrasound-responsive bubbles to the fracture site. Ultrasound stimulation of bubbles causes them to resonate. In our preliminary data, we have shown that this results in the release of bubble-associated drugs, improved uptake of compounds in nearby cells, and mechanostimulation of cells through either direct membrane interaction or via shear of extracellular media. More recently we have found that acoustically-responsive bubbles can be fabricated in the nanometre size range and that they accumulate at fracture sites. This means we will be able to localise drug-containing nanobubbles at bone fracture sites, before remotely stimulating them with ultrasound to both release their cargo and mechanostimulate the surrounding tissue.
In this studentship, the student will first develop and optimise nanobubbles and ultrasound-responsive nanodroplet formulations (which cavitate to form microbubbles upon ultrasound stimulation) to demonstrate that these agents can simultaneously be used to deliver drugs and to mechanostimulate stem cells, inducing their differentiation in in vitro models. The student will then determine which size and chemical characteristics lead to localisation of bubbles to the fracture callus post-injury. Finally, the student will test in vivo whether acoustic stimulation of fracture callus-localised bubbles affects the rate and quality of bone fracture healing. The student will train with experts in stem cell biology, mechanobiology, nanotechnology and ultrasonics from established experts at University of Southampton
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| MR/R502261/1 | 01/10/2017 | 30/09/2022 | |||
| 1960951 | Studentship | MR/R502261/1 | 01/10/2017 | 31/03/2021 | Sara Ferri |