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

腹部手术后，通常会形成不需要的疤痕组织，将腹部器官捆绑在一起。这被称为术后粘连，在大多数患者中都会发生。这种粘连通常非常严重或持续，以至于会引起一系列并发症，包括疼痛、不适、更严重的肠梗阻和女性不孕。术后粘连一旦形成，唯一有效的治疗方法就是矫正手术。治疗术后粘连相关问题的费用非常昂贵，在英国每年约为5000万英镑。因此，预防术后粘连具有重要的价值。迄今为止，还没有为此目的成功开发出有效的药物。相反，越来越多的生物材料产品，包括人造薄膜和凝胶，已经被生产出来供医院使用。这些产品可以将受损组织与周围组织分离，限制粘连的形成。话虽如此，这些产品只对一半的患者有效。因此，对于预防术后粘连形成的更有效的治疗方法有很大的需求。基于我们最近的科学发现，我们提出了一种防止术后粘连的新技术，使用微米大小的人造球体，这些球体旨在聚集在受损组织表面并防止粘连的形成。我们将使用一种已被证明对患者安全的生物材料。与目前的预防方法相比，这种先进的技术在更大的有效性、更高的特异性和更少的并发症方面具有一系列显著的优势。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，该项目的主要目的是建立可靠的临床前证据，证明这种有希望的治疗方法在预防术后粘连形成方面的安全性和有效性。我们将优化颗粒大小、设计和剂量，并在多种临床相关的术后粘连模型中证实其安全性和有效性。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，使其进入下一阶段的早期临床应用。此外，该项目将为了解术后粘连的形成、巨噬细胞生物学以及生物材料和工程技术提供重要的、以前未知的科学知识。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，这个项目有很大的潜力使科学家、病人、医生、NHS和社会受益。由于相关市场巨大，这项创新技术在术后粘连方面也有商机。

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.