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害相关的疾病，会影响数百万的人 每年。当前的药物，包括镇痛药和抗炎药，仅减轻症状 但是，在使用替换软骨自动或异晶型手术方法的手术方法时，请勿治愈这种疾病 感染，供体发病率，免疫排斥和组织供应有限的问题。在这方面， 基于生物材料支架，干细胞和生物学生长的再生工程方法 构建人造替代软骨组织的因素已成为一个重要领域。而成长的因素 这些化学物质对其有毒和副作用引起了重大关注。或者， 已知电刺激（ES）对促进骨骼和软骨生长具有重要作用。 由于生物电性是活生物体的内在物理信号，因此ES的使用大概提供了更多 自然诱导软骨生长的方法。但是，虽然体外电刺激器不是 有效的，植入的设备依靠有毒电池，需要侵入性手术才能清除，这很容易 损害愈合组织。在这方面，我们开发了一种新型的可生物降解压电纳米纤维 脚手架，由PLLA（Poly-L-lactide）制成，表明该脚手架可以在施加的关节下自生ES 在小动物模型中治愈软骨缺陷的力量。然而，仍然存在重要的问题仍然需要 解决。这些问题是（1）最佳刺激和最佳的压电生物降解 脚手架用于软骨愈合，（2）体育锻炼的脚手架是否可以治愈主要软骨 大动物的缺陷。在这里，我们首次提出了一种新的可生物降解压电 纳米复合软骨移植物（含有PLLA和氧化镁 - MGO纳米颗粒），并研究 最佳的身体运动，以获得一种新型的再生方法，可以治愈关键大小 大动物的软骨缺陷。彼此之间，这项工作的设计具有三个特定的目标。目标1是 表征所提出的可生物降解的压电复合材料支架体外以获得良好的替代品 软骨移植物。目标2是研究和评估最佳体育锻炼（持续时间，频率和强度），并且 最佳的复合支架，可在兔子中最佳治愈软骨缺陷。目标3是研究和证明 大型动物模型（绵羊）中的软骨愈合。第一个里程碑（1。5年以内）是找出最好的里程碑 在体外具有所需性能的压电支架。 3。5年后的第二个里程碑是找出 最佳的体育锻炼和脚手架，以治愈兔子的软骨缺陷。最后一个里程碑（5年后）是 证明MGO/PLLA支架具有衍生的最佳关节载荷（N/M2）和跑步机训练的能力 治愈绵羊的关键大小软骨缺陷。