Biodegradable Piezoelectric Nanocomposite Scaffold with Physical Exercise to Heal Major Cartilage Defects in Large Animals

可生物降解的压电纳米复合支架与体育锻炼可治愈大型动物的主要软骨缺陷

• 批准号: 10634516
• 负责人: Thanh Nguyen
• 金额: $ 42.26万
• 依托单位: UNIVERSITY OF CONNECTICUT STORRS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-03 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10634516
• 关键词: Address; Affect; Allografting; American; Analgesics; Animal Model; Animals; Anti-Inflammatory Agents; Area; Autologous Transplantation; Biocompatible Materials; Biodegradation; Biological; Body Weight; Cartilage; Charge; Chemicals; Clinical; Defect; Degenerative polyarthritis; Devices; Disease; Electric Stimulation; Electricity; Electrospinning; Engineering; Environment; Excision; Exercise; Exhibits; Foundations; Frequencies; Grant; Growth; Growth Factor; Human; Immune; Implant; In Vitro; Infection; Inflammation; Joints; Magnesium Oxide; Mechanics; Medicine; Methods; Morbidity - disease rate; Motion; Nanofiber Scaffold; Natural regeneration; Operative Surgical Procedures; Organism; Oryctolagus cuniculus; Persons; Pharmaceutical Preparations; Physical Exercise; Physiological; Physiology; Process; Property; Regenerative engineering; Self Stimulation; Sheep; Signal Transduction; Site; Stress; Symptoms; Technology; Therapeutic Effect; Time; Tissues; Toxic effect; Training; United States National Institutes of Health; Work; arthropathies; articular cartilage; biodegradable scaffold; bioelectricity; bioscaffold; bone; cartilage regeneration; cartilage transplantation; design; healing; implantable device; joint loading; mechanical properties; nanocomposite; nanofiber; nanoparticle; novel; poly(lactic acid); pressure; reduce symptoms; regenerative approach; research clinical testing; scaffold; side effect; stem cells; success; tissue support frame; treadmill training

Abstract Osteoarthritis (OA), a disease associated with cartilage damages inside the joints, affects millions of people every year. The current medicines, including analgesics and anti-inflammation drugs only alleviate symptoms but do not cure the disease while surgical methods to use replacement cartilage auto- or allo-grafts struggle with the problems of infection, donor-site morbidity, immune-rejection and limited tissue supply. In this regard, regenerative engineering approaches which are based on biomaterial scaffolds, stem cells and biological growth factors to construct artificial replacement cartilage tissues have become an important field. While growth factors are powerful, these chemicals pose a significant concern regarding to their toxic and side effects. Alternatively, electrical stimulation (ES) has been known to exhibit a significant effect on promoting bone and cartilage growth. As bioelectricity is an intrinsic physiological signal of living organisms, the use of ES presumably, offers a more natural approach for inducing cartilage growth. However, while extracorporeal electrical stimulators are not effective, implanted devices rely on toxic batteries, requiring invasive surgery for removal, which can easily damage the healing tissues. In this regard, we have developed a novel biodegradable piezoelectric nanofiber scaffold, made of PLLA (Poly-L-lactide) and shown that this scaffold can self-generate ES under applied joint force to heal cartilage defects in small animal models. Yet remaining important questions still need to be addressed. These questions are (1) what the optimal stimulation and the best piezoelectric biodegradable scaffold are for cartilage healing and (2) whether the scaffold with physical exercise can heal the major cartilage defects in large animals. Here, we propose, for the first time, a new biodegradable piezoelectric nanocomposite cartilage-graft (containing PLLA and magnesium oxide – MgO nanoparticles), and study an optimal physical-exercise to obtain a novel regenerative approach which can heal critical-sized cartilage defects in large animals. Accordingly, the work is designed with three specific aims; Aim 1 is to characterize the proposed biodegradable piezoelectric composite scaffold in vitro to obtain a good replacement cartilage graft. Aim 2 is to study and assess optimal physical exercise (duration, frequency, and intensity) and optimal composite scaffolds for the best healing of cartilage defects in rabbits. Aim 3 is to study and demonstrate cartilage healing in large animal model (sheep). The first milestone (in 1.5 years) is to find out the best piezoelectric scaffold with desired properties in vitro. The second milestone after 3.5 years is to find out the optimal physical training and scaffold to heal cartilage defects in rabbits. The final milestone (after 5 years) is to demonstrate the ability of the MgO/PLLA scaffold with derived optimal joint load (N/m2) and treadmill training to heal critical-sized cartilage defects in sheep.

抽象的 骨关节炎 (OA) 是一种与关节内软骨损伤相关的疾病，影响数百万人 目前的药物，包括止痛药和消炎药，只能缓解症状。 但并不能治愈这种疾病，而使用自体或同种异体软骨替代软骨的手术方法却难以治愈 感染、供体部位发病率、免疫排斥和组织供应有限等问题。 基于生物材料支架、干细胞和生物生长的再生工程方法 构建人工替代软骨组织的因子已成为一个重要的领域。 虽然这些化学物质威力强大，但其毒性和副作用引起了人们的严重关注。 众所周知，电刺激 (ES) 对促进骨骼和软骨生长具有显着效果。 由于生物电是生物体固有的生理信号，因此使用 ES 大概可以提供更多信息 然而，体外电刺激器却不是诱导软骨生长的自然方法。 有效的植入设备依赖有毒电池，需要进行侵入性手术才能移除，这很容易 在这方面，我们开发了一种新型的可生物降解的压电纳米纤维。 由 PLLA（聚左旋丙交酯）制成的支架，表明该支架可以在应用关节下自行生成 ES 然而，仍然需要解决一些重要问题。 这些问题是最优的（1）什么是最好的刺激和压电可生物降解。 支架是用于软骨愈合的；（2）支架配合体育锻炼是否可以愈合主要软骨 在这里，我们首次提出了一种新的可生物降解压电材料。 纳米复合软骨移植物（含有 PLLA 和氧化镁 - MgO 纳米颗粒），并进行研究 最佳的身体锻炼以获得一种新颖的再生方法，可以治愈临界尺寸 因此，这项工作的设计目标有三个： 体外表征所提出的可生物降解压电复合支架以获得良好的替代品 目标 2 是研究和评估最佳体育锻炼（持续时间、频率和强度）和 目标 3 是研究和证明最适合兔子软骨缺损愈合的复合支架。 大型动物模型（绵羊）的软骨愈合第一个里程碑（1.5 年内）是找出最好的。 3.5年后的第二个里程碑是找出在体外具有所需特性的压电支架。 治愈兔子软骨缺陷的最佳体能训练和支架 最后的里程碑（5年后）是 证明 MgO/PLLA 支架具有导出的最佳关节负荷 (N/m2) 和跑步机训练的能力 治愈绵羊临界尺寸的软骨缺损。