Bioactive adhesive material for early vaginal wall detachment in pelvic organ prolapse

项目总结 早期阴道壁脱离常导致盆腔器官脱垂(POP)。POP是人类社会的常见病。 老年妇女的高发病率与治疗有关。大约30%-40%的女性可能会经历 这种情况，到80岁左右会有20%左右需要接受矫正手术。但是，当前 用于矫正手术的合成材料一直很受欢迎，但可能会导致严重的并发症，如 被FDA在两次通知(2008,2011)中认可，并有较高的脱垂复发率。 此外，由于识别晚和可变，POP治疗被推迟到晚期 症状学。为了减少POP的发病率和治疗成本，解决早期阴道壁的策略 超脱以防止民研计划的发展将是非常可取的。这种预防性治疗可能会使用 一种合适的可生物降解的生物黏附材料，用于将分离的阴道壁重新附着到骨盆肌肉上 以防止阴道前壁和阴道尖部进一步脱落和脱落导致POP。 我们的初步工作表明，一种以贻贝为灵感的可生物降解粘合剂是实现这一目标的很好的候选材料。 预防目标，但在粘接强度性能和组织耐久性方面还需要进一步提高。在这 项目，我们的目标是开发一种由贻贝启发的粘合剂和可生物降解的新型粘合剂材料 专用于早期阴道壁脱离的纳米颗粒。为了实现这一目标，提出了三个具体目标。 在目标1中，我们将通过改变其化学成分来制备和优化我们现有的可生物降解的纳米级粘合剂。 结构、组分浓度、纳米颗粒含量和表面。在目标2中，我们将评估 使用体外组织模型和评估材料的生物安全性、粘附性的纳米块的粘接强度 使用大鼠模型进行体内力量和组织生长的研究。在目标3中，我们将加入一种细胞招募趋化因子 进入粘合剂，它可以招募干细胞，促进新组织的形成，永久增强 骨盆底和肌肉之间的附着物。我们将进一步测定这种生物活性粘合剂的疗效。 使用的是老鼠模型。提出了三个方面的创新点。第一个是预防战略的新概念 早期处理阴道壁脱离，降低POP的发生率，可提高患者的生活质量。 女性患者，节省了治疗费用。第二是实现了一种新型的可生物降解的 粘合材料系统。它将提供快速和坚固的粘合剂来加固脱离的阴道壁 骨盆肌肉，并允许新组织向内生长。纳米颗粒可提高粘接强度和粘接强度 也被用作传递生物功能分子的载体。第三，这种纳米级粘合剂还可以 作用于细胞募集和组织再生。这一项目的成功结果将提供一种新颖的 早期阴道壁脱离的治疗策略，以防止POP的发生 降低发病率和相关的治疗成本。所开发的材料和方法可用于 用于其他生物医学应用，如组织胶和伤口愈合。

Project summary Early vaginal wall detachment often results in pelvic organ prolapse (POP). POP is a common disease in the aging woman with a high morbidity rate related to treatment. Approximately 30-40% of women may experience this condition, and by 80 years-old about 20% or so will need to undergo corrective surgery. However, current synthetic materials for corrective surgery have been popular but can lead to severe complications as recognized by the FDA in two notifications (2008, 2011) along with a high prolapse recurrence rate. Furthermore, the POP treatment is delayed until advanced stages due to late recognition and variable symptomatology. To reduce POP morbidity and treatment cost, a strategy to address early vaginal wall detachment to prevent POP development would be highly desirable. Such a preventive treatment could employ an appropriate biodegradable bio-adhesive material to reattach the detached vaginal wall to the pelvic muscle in order to prevent further drop and detachment of the anterior vaginal wall and vaginal apex resulting in POP. Our preliminary work indicates that a biodegradable mussel-inspired adhesive is a good candidate to attain this preventive goal, but it needs further improvement in adhesive strength properties and tissue durability. In this project, our goal is to develop a novel adhesive material from mussel-inspired adhesive and biodegradable nanoparticles specific for early vaginal wall detachment. To realize this goal, three specific aims are proposed. In Aim 1, we will prepare and optimize our current biodegradable nanoblend adhesive by altering its chemical structure, component concentrations, nanoparticle contents and surface. In Aim 2, we will evaluate the adhesive strength of the nanoblend using an ex vivo tissue model and assess the material biosafety, adhesive strength and tissue growth in vivo using a rat model. In Aim 3, we will incorporate a cell recruiting chemokine into the adhesive, which can recruit stem cells to promote new tissue formation to permanently enhance the attachment between pelvic floor and muscle. We will further determine the efficacy of this bioactive adhesive using a rat model. Three innovative aspects are proposed. The first is the novel concept of prevention strategy to manage early vaginal wall detachment to reduce the morbidity of POP, which can improve the life quality of the women patients and save therapy costs. The second is the implementation of a novel biodegradable adhesive material system. It will provide rapid and robust adhesive to reinforce the detached vaginal wall from the pelvic muscle, and allow new tissue ingrowth. The nanoparticles can increase the adhesive strength and also served as carriers to deliver biofunctional molecules. The third is that this nanoblend adhesive can also works for cell recruitment and tissue regeneration. The successful outcome of this project will provide a novel strategy to treat patients with early vaginal wall detachment to prevent POP occurrence, thus resulting in reduced morbidity and associated treatment cost. The developed materials and methodologies could be used for other biomedical applications such as tissue glue and wound healing.