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

生物活性粘合材料治疗盆腔器官脱垂早期阴道壁脱离

• 批准号: 10328255
• 负责人: Yi Hong
• 金额: $ 31.58万
• 依托单位: UNIVERSITY OF TEXAS ARLINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10328255
• 关键词: Acrylates; Address; Adhesions; Adhesives; Affect; Age; Aging; Alginates; Animal Model; Anterior; Attenuated; Bladder; Cells; Cervix Uteri; Chemical Structure; Clinic; Data; Defect; Development; Disease; Drops; Dyspareunia; Effectiveness; Environment; FDA approved; Family suidae; Fibrin; Fibrin Tissue Adhesive; Functional disorder; Glues; Goals; Growth; Implant; In Vitro; Infective cystitis; Injectable; Intestines; Lead; Life; Mechanics; Methodology; Modeling; Morbidity - disease rate; Muscle; Mussels; Notification; Operative Surgical Procedures; Outcome; Pain; Patients; Pelvic Floor Muscle; Pelvic floor structure; Pelvis; Pessaries; Polymers; Prevention; Prevention strategy; Preventive; Preventive treatment; Property; Ptosis; Quality of life; Rattus; Rectum; Recurrence; Repeat Surgery; Safety; Sheep; Silicon Dioxide; Skin; Smooth Muscle Myocytes; Surface; Surgical incisions; Symptoms; System; Testing; Time; Tissue Model; Tissues; Treatment Cost; Vagina; Woman; Work; abdominal wall; adhesive polymer; base; biodegradable polymer; biomaterial compatibility; care costs; chemokine; cost; crosslink; cytotoxicity; design; effectiveness evaluation; experience; healing; improved; in vivo; innovation; interest; middle age; nanoparticle; novel; novel strategies; older women; pelvic organ prolapse; pressure; prevent; procedure cost; recruit; repaired; replacement tissue; safety assessment; stem cells; symptomatology; tissue glueing; tissue regeneration; translational applications; wound; wound healing

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.

项目概要 早期阴道壁脱离常常导致盆腔器官脱垂（POP）。 POP是一种常见疾病 与治疗相关的高发病率的老年女性。大约 30-40% 的女性可能会经历 这种情况，到了80岁左右大约20%左右就需要接受矫正手术。然而，目前 用于矫正手术的合成材料很受欢迎，但可能会导致严重的并发症，例如 FDA 在两次通知（2008 年、2011 年）中认可了这种脱垂复发率。 此外，由于识别迟缓和变量的存在，POP 治疗被推迟到晚期。 症状学。为了降低 POP 发病率和治疗成本，解决早期阴道壁问题的策略 非常需要采取分遣队来防止持久性有机污染物的发展。这种预防性治疗可以采用 适当的可生物降解的生物粘合材料，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进一步下垂、脱离而导致POP。 我们的初步工作表明，可生物降解的贻贝粘合剂是实现这一目标的良好候选者 预防性目标，但需要进一步提高粘合强度性能和组织耐久性。在这个 项目，我们的目标是开发一种新型粘合材料，以贻贝为灵感的粘合剂和可生物降解的粘合剂 专门针对早期阴道壁脱离的纳米颗粒。为实现这一目标，提出了三个具体目标。 在目标 1 中，我们将通过改变其化学性质来制备和优化现有的可生物降解纳米混合粘合剂 结构、成分浓度、纳米颗粒含量和表面。在目标 2 中，我们将评估 使用离体组织模型评估纳米混合物的粘合强度，并评估材料的生物安全性、粘合性 使用大鼠模型进行体内强度和组织生长。在目标 3 中，我们将纳入细胞募集趋化因子 进入粘合剂中，它可以招募干细胞来促进新组织的形成，从而永久增强 骨盆底和肌肉之间的附着。我们将进一步确定这种生物活性粘合剂的功效 使用大鼠模型。提出了三个创新点。一是预防策略理念新颖 处理早期阴道壁脱离，降低 POP 的发病率，从而提高患者的生活质量 为女性患者节省治疗费用。第二个是实施新型可生物降解的 粘合材料系统。它将提供快速而坚固的粘合剂，以加固分离的阴道壁 骨盆肌肉，并允许新的组织向内生长。纳米粒子可以增加粘合强度 还充当传递生物功能分子的载体。第三，这种纳米混合粘合剂还可以 适用于细胞招募和组织再生。该项目的成功成果将为 治疗早期阴道壁脱离患者的策略以预防 POP 的发生，从而导致 降低发病率和相关治疗费用。可以使用开发的材料和方法 用于其他生物医学应用，例如组织胶和伤口愈合。