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

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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.