Injectable Nanoparticles for Soft Tissue Recovery and Strength Enhancement

在美国，每年有超过3200万例韧带和肌腱的创伤性和重复性运动损伤，耗资300亿美元。扭伤（韧带损伤）和拉伤（肌腱和肌肉损伤）占到急诊室的570万人次。2002年，大约20万美国人需要进行韧带重建手术，花费超过50亿美元。关节脱位在结缔组织疾病患者中更为常见，比如埃勒斯-丹洛斯综合征（EDS），这是一组遗传性结缔组织疾病，会导致胶原蛋白产生缺陷。EDS患者经常经历关节脱位，不稳定的关节可能会疼痛和虚弱。作为扭伤、拉伤和关节脱位的解决方案，本项目提出了一种可注射治疗方法，使组织恢复到正常长度，并使用天然的粘合形成剂加强组织，以防止再次损伤/未来损伤。该项目还将在夏季和整个学年为代表性不足的第一代本科生创造研究机会。它还将为服务不足的小学中代表性不足的学生创造机会，让他们通过演讲和动手实验来学习生物医学工程。该项目的总体目标是研究热敏聚合物和交联剂的组合，通过恢复受损肌腱和韧带的强度和原始长度来快速稳定关节。这将通过研究聚（n-异丙基丙烯酰胺）（pNIPAm）的收缩和表没食子儿茶素-3-没食子酸酯（EGCG）交联的体内有效性来完成。研究方法分为三个方面。首先，胶原蛋白结合的可收缩纳米粒子将被创造和评估。这一步骤将改变纳米颗粒的组成和pNIPAm的浓度，以最大限度地收缩和结合胶原纤维。其次，将评估EGCG的释放及其对细胞行为和组织强度的影响。EGCG的浓度将会产生最大的胶原交联，同时对周围细胞无毒。第三，评估纳米颗粒在体内的收缩和组织强化能力。基于前两项任务的纳米颗粒将被注射到受损肌腱模型中。注射后，将评估其对步态、注射后长度和力量的影响。如果成功，这种创新的疗法将通过增强力量、促进伤口愈合和快速稳定受损关节而使数百万人受益。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

In the U.S., there are over 32 million traumatic and repetitive motion injuries to ligaments and tendons each year, costing $30 billion. Sprains (ligament injuries) and strains (tendon and muscle injuries) account for 5.7 million visits to emergency rooms. In 2002, approximately 200,000 Americans required ligament reconstructive surgery costing over $5 billion. Joint dislocations are more frequent for those with connective tissue disorders like Ehlers-Danlos Syndrome (EDS), a group of genetic connective tissue disorders that cause defective collagen production. Patients with EDS frequently experience joint dislocations from unstable joints that can be painful and debilitating. As a solution to sprains, strains, and joint dislocations, this project proposes an injectable therapy to return the tissue to its normal length and strengthen it using a natural, bond-forming agent to prevent reinjury/future injury. This project will also create research opportunities for underrepresented and first-generation undergraduate students during the summers and throughout the school year. It will also create opportunities for underrepresented students in underserved elementary schools to learn about biomedical engineering through presentations and hands-on experiments.The overall goal of this project is to investigate the combination of a thermosensitive polymer and crosslinking agent to quickly stabilize joints by restoring strength and original length to damaged tendons and ligaments. This will be accomplished by studying the contraction of poly(N-isopropylacrylamide) (pNIPAm) and the effectiveness of epigallocatechin-3-gallate (EGCG) crosslinking in vivo. The research approach is divided into three areas. First, collagen-binding contractile nanoparticles will be created and evaluated. This step will alter nanoparticle composition and pNIPAm concentration to maximize contraction and bind to collagen fibers. Second, the EGCG release and its effect on cell behavior and tissue strength will be evaluated. The concentrations of EGCG that create maximum collagen crosslinking, while remaining nontoxic to surrounding cells will be discovered. Third, the contractile and tissue strengthening ability of the nanoparticles in vivo will be evaluated. Nanoparticles with compositions based on the earlier two tasks will be injected into a damaged tendon model. After injection, they will be evaluated for their effect on gait, length after injection, and strength. If successful, this innovative, therapy would benefit millions of people by increasing strength, improving wound healing, and quickly stabilizing damaged joints.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.