Ultrasound-triggered mineralization: building a technology for non-union bone fracture repair

Non-union bone fractures are a clinical complication that occurs when broken bones fail to heal after a prolonged period of time,
which places a tremendous burden upon the patient, society, and the healthcare economy. The most common treatment involves the
introduction of solid grafts into the defect site, however, these methods require highly invasive surgical procedures that have clinical
and economic drawbacks. ULTRABONE will output an innovative method with the potential to form a new regenerative procedure to
accelerate and improve the healing of non-union bone fractures via minimally invasive surgery. This method will use focused
ultrasound to remotely trigger the precipitation of apatite through stimulated release of liposomal ions. This remote mineralization
will be incorporated within a granular hydrogel composed of high concentration collagen. This biomaterial will provide the
rheological properties for percutaneous injection and in situ setting, the interstitial porosity and material cues to support cell invasion
and vascularization, and the high-density fibrillar network to nucleate and grow apatite at a size, distribution, and morphology that is
present in native bone. This work program will develop the concept of ultrasound-triggered mineralization, integrate it within the
granular hydrogel, and model the regenerative capability of the system in vitro, in readiness for future preclinical testing.