Fibrin-targeting PLGA microspheres for prevention of post-operative peritoneal adhesions; a pre-clinical proof of concept study

腹部手术后，经常会形成不必要的疤痕组织，将腹部器官捆绑在一起。这被称为术后粘连，发生在大多数患者中。粘连往往是如此过度或持久，它可以导致一系列并发症，包括疼痛，不适和更严重的肠梗阻和女性不孕症。术后粘连一旦形成，唯一有效的治疗方法是矫正手术。治疗术后粘连相关问题的成本极其昂贵，在英国计算为> 5000万英镑/年。因此，预防术后粘连具有重要价值。到目前为止，还没有成功开发出有效的药物用于此目的。相反，越来越多的生物材料产品，包括人造薄膜和凝胶，已被生产用于医院。这些产品可以将受损组织与周围组织分离，限制粘连形成。话虽如此，这些产品只对一半接受治疗的患者有效。因此，对于预防术后粘连形成的更有效的治疗存在很大的未满足的需求。基于我们最近的科学发现，我们提出了一种新的技术，以防止术后粘连使用微米大小的人造球，其目的是聚集在受损组织表面，防止粘连形成。我们将使用一种已被证明可安全用于患者的生物材料。这种先进的技术与目前的预防方法相比具有一系列显著的优势，包括更高的有效性，更高的特异性和更少的并发症。事实上，我们的初步研究表明，这项技术减少了腹部手术后的粘连，没有任何不良事件。因此，本项目的主要目的是建立可靠的临床前证据，证明这种有前途的治疗方法预防术后粘连形成的安全性和有效性。我们将优化颗粒尺寸、设计和剂量，并确认其在多种临床相关术后粘连模型中的安全性和有效性。我们还将系统地探索与这种治疗的安全性和益处相关的生物学见解。所获得的结果将验证这一尖端先进技术的进展，以下一阶段的发展，以早期临床采用。此外，该项目将提供重要的，以前未知的科学知识，以了解术后粘连的形成，巨噬细胞生物学，生物材料和工程技术。这些将阐明新的科学观念，为未来的医学和科学研究铺平道路。因此，该项目具有巨大的潜力，使科学家，患者，医生，NHS和社会受益。由于相关市场巨大，这种用于术后粘连的创新技术也存在商业机会。

After abdominal surgery, an unwanted scar tissue is frequently formed, binding the abdominal organs together. This is called a post-operative adhesion, which occurs in most patients. The adhesion is often so excessive or persistent that it can cause a range of complications, including pain, discomfort and more seriously bowel obstruction and female infertility. The only effective therapy of post-surgical adhesions, once developed, is corrective surgery. The cost for treating post-surgical adhesion-related problems is extremely expensive, calculated to be >£50 million/year in the UK. Therefore, prevention of post-surgical adhesions is of great value. To date, no effective drug has been successfully developed for this purpose. Instead, an increasing number of biomaterial products, including artificial films and gels, have been produced for use in hospitals. These products can separate the damaged tissues from surrounding tissues, limiting the adhesion formation. Having said this, these products are only effective in half of the patients treated. Therefore, there is a great unmet need for a more effective treatment to prevent post-operative adhesion formation. Based on our recent scientific discovery, we propose a new technology to prevent post-operative adhesions using micrometre-sized man-made spheres, which are designed to gather at the damaged tissue surface and prevent adhesion formation. We will use a biomaterial that has proven safe to use in the patients. This advanced technology has a range of significant advantages over the current preventative methods, in terms of greater effectiveness, higher specificity, and less complications. Indeed, our pilot study suggested that this technology reduced adhesions after abdominal operation without any adverse event. Thus, the primary aim of this project is to establish robust pre-clinical evidence for the safety and usefulness of this promising treatment to prevent post-operative adhesion formation. We will optimize the particle size, design, and dose, and confirm its safety and effectiveness in multiple clinically relevant models of post-operative adhesions. We will also systematically explore the biological insights relevant to the safety and benefits of this treatment. The results obtained will validate the progression of this cutting-edge advanced technology to the next stage of development toward early clinical adoption. In addition, this project will provide important, previously unknown scientific knowledge to understand the formation of post-operative adhesions, macrophage biology, and biomaterial and engineering technology. These will shed light on the new scientific perceptions, which will pave the way to future medical and scientific research. Therefore, this project has great potential to benefit the scientists, patients, doctors, the NHS, and society. There are also commercial opportunities associated with this innovative technology for post-operative adhesion as the relevant market is huge.