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

骨不连是指骨折长期不愈合，给患者、社会和医疗保健经济带来巨大负担的临床并发症。最常见的治疗方法包括向缺损处引入固体移植物，然而，这些方法需要高度侵入性的外科手术，具有临床和经济上的缺点。ULTRABONE将输出一种创新的方法，有可能形成一种新的再生程序，通过微创手术加速和改善骨不连骨折的愈合。这种方法将使用聚焦超声通过脂质体离子的刺激释放来远程触发磷灰石的沉淀。这种远程矿化将被结合到由高浓度胶原蛋白组成的颗粒状水凝胶中。这种生物材料将提供用于经皮注射和原位植入的热流变性能、支持细胞侵袭和血管形成的间质孔隙率和材料线索，以及以天然骨中存在的尺寸、分布和形态成核和生长磷灰石的高密度纤维网络。这项工作计划将开发超声触发矿化的概念，将其集成到颗粒水凝胶中，并对系统的体外再生能力进行建模，为未来的临床前测试做好准备。

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 theintroduction of solid grafts into the defect site, however, these methods require highly invasive surgical procedures that have clinicaland economic drawbacks. ULTRABONE will output an innovative method with the potential to form a new regenerative procedure toaccelerate and improve the healing of non-union bone fractures via minimally invasive surgery. This method will use focusedultrasound to remotely trigger the precipitation of apatite through stimulated release of liposomal ions. This remote mineralizationwill be incorporated within a granular hydrogel composed of high concentration collagen. This biomaterial will provide therheological properties for percutaneous injection and in situ setting, the interstitial porosity and material cues to support cell invasionand vascularization, and the high-density fibrillar network to nucleate and grow apatite at a size, distribution, and morphology that ispresent in native bone. This work program will develop the concept of ultrasound-triggered mineralization, integrate it within thegranular hydrogel, and model the regenerative capability of the system in vitro, in readiness for future preclinical testing.