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，随着人口老龄化，这一问题将变得更加严重。延迟的骨愈合和延长的康复每年为欧洲经济带来390亿英镑的骨损伤成本，大约15万例手腕、脊椎和髋部骨折每年使英国损失21亿英镑。一部分骨折无法通过目前的临床干预措施适当愈合，这些干预措施包括机械固定或更罕见的生物材料和/或生物活性剂。因此，迫切需要新的治疗方法。到目前为止，还没有临床上批准的骨折的全身治疗。我们正在制定这样的方法。在初步工作中，我们发现已知大小的纳米颗粒（NP）在骨折后特定窗口期间在损伤部位积累。我们已经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递送到损伤部位，而不破坏愈合组织，愈合组织的完整性通常对令人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，这些观察现在提供了远程和主动控制药物释放和骨修复中的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.