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

骨不连骨折是骨折长时间不能愈合的临床并发症，给患者、社会和医疗经济带来了巨大的负担。最常见的治疗包括将实体移植物引入缺损部位，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将推出一种创新的方法，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愈合骨折的愈合。该方法将使用聚焦超声通过刺激脂质体离子的释放来远程触发磷灰石的沉淀。这种远程矿化将纳入由高浓度胶原蛋白组成的颗粒水凝胶。这种生物材料将提供经皮注射和原位设置的流变特性，间质孔隙度和材料提示支持细胞侵入和血管化，高密度纤维网络使磷灰石在天然骨中具有成核和生长的大小、分布和形态。这项工作计划将发展超声触发矿化的概念，将其整合到颗粒水凝胶中，并在体外模拟系统的再生能力，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.