Bubbles for biofilm: acoustic stimulation for drug delivery in fracture repair

骨折及其相关并发症是一个主要的社会问题，随着我们人口的老龄化，这个问题将变得更加严重。延迟的骨骼愈合和延长的康复每年给欧洲经济造成390亿英镑的骨损伤成本，大约150,000个手腕、脊柱和髋部骨折每年花费英国21亿英镑。目前的临床干预措施，包括机械固定，或者更罕见的是，使用生物材料和/或生物活性物质，未能适当地愈合一部分骨折。因此，迫切需要新的治疗方法。到目前为止，还没有临床批准的全身治疗骨折的方法。我们正在开发这样一种方法。在初步工作中，我们发现，在特定的窗口骨折后，已知大小的纳米颗粒(NPs)在损伤部位积累。我们使用这种方法在骨折愈合的不同阶段选择性地将治疗分子输送到损伤部位，而不破坏愈合组织，愈合组织的完整性通常对满意的结果至关重要(图1)。除了能够在骨折部位被动释放药物外，这些观察现在还提供了远程和主动控制骨修复中的药物释放和组织刺激的令人兴奋的机会。

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 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 (Figure 1). 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.