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.

项目摘要 早期的阴道壁脱离通常会导致骨盆器官脱垂（POP）。流行是一种常见疾病 与治疗相关的高发病率的老年女性。大约30-40％的女性可能会遇到 这种情况，到80岁左右，需要进行纠正术。但是，当前 用于纠正手术的合成材料很受欢迎，但可能导致严重的并发症 由FDA在两次通知（2008，2011）中识别，以及较高的脱垂复发率。 此外，流行疗法被推迟到由于较晚识别和可变而导致高级阶段 症状学。为了降低流行发病率和治疗成本，解决早期阴道墙的策略 防止流行音乐发展的分离将是非常可取的。这样的预防治疗可以采用 一种适当的可生物降解的生物粘附材料，可将脱落的阴道壁重新安装到骨盆肌肉 为了防止进一步的掉落和脱离阴道壁和阴道顶点，导致流行。 我们的初步工作表明，可生物降解的贻贝启发的粘合剂是实现这一目标的好候选者 预防目标，但需要进一步改善粘合强度性能和组织耐用性。在这个 项目，我们的目标是从贻贝启发的粘合剂和可生物降解的新型粘合剂材料开发出一种新颖的粘合剂材料 纳米颗粒针对早期阴道壁脱离。为了实现这一目标，提出了三个具体目标。 在AIM 1中，我们将通过更改其化学物质来准备和优化当前可生物降解的纳米蓝色粘合剂 结构，组件浓度，纳米颗粒含量和表面。在AIM 2中，我们将评估 使用离体组织模型的纳米蓝色的粘合力强度，并评估材料生物安全，粘合剂 使用大鼠模型在体内的强度和组织生长。在AIM 3中，我们将合并一个募集趋化因子的细胞 进入粘合剂，可以募集干细胞以促进新组织形成以永久增强 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。提出了三个创新的方面。首先是预防策略的新颖概念 管理早期阴道墙分离以减少流行的发病率，这可以提高生活质量 女性患者并节省治疗费用。第二个是实施新颖的可生物降解 粘合物材料系统。它将提供快速，可靠的粘合剂，以增强从 骨盆肌肉，并允许新的组织向内生长。纳米颗粒可以提高粘合强度和 还用作携带生物功能分子的载体。第三个是这种纳米蓝色粘合剂也可以 用于细胞募集和组织再生的工作。该项目的成功结果将提供小说 治疗早期阴道壁脱脱患者以防止发生流行的策略，从而导致 发病率降低和相关的治疗成本。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。