Bionic Self-Stimulated Cartilage

仿生自刺激软骨

• 批准号: 9375269
• 负责人: Thanh Nguyen
• 金额: $ 23.93万
• 依托单位: UNIVERSITY OF CONNECTICUT STORRS
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-15 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9375269
• 关键词: Acids; Allografting; American; Attention; Autologous; Autologous Transplantation; Biocompatible Materials; Biological; Bionics; Bone Regeneration; Cartilage; Chondrocytes; Defect; Degenerative polyarthritis; Devices; Disease; Electric Stimulation; Electricity; Engineering; Exhibits; FDA approved; Feedback; Film; Graft Enhancements; Growth; Harvest; Hyaline Cartilage; Hybrids; Immune response; Implant; In Vitro; Joints; Knee joint; Knowledge; Mechanics; Modeling; Molecular Weight; Morbidity - disease rate; Natural regeneration; Operative Surgical Procedures; Oryctolagus cuniculus; Output; Overdose; Performance; Polymers; Process; Property; Reporting; Science; Signal Transduction; Site; Technology; Thick; Tissues; Weight-Bearing state; biodegradable polymer; bone; cartilage cell; cartilage regeneration; cartilage repair; direct application; experimental study; graft healing; healing; implantable device; implantation; in vivo; innovation; joint injury; knee replacement arthroplasty; medical implant; nano; novel strategies; osteochondral tissue; polyvinylidene fluoride; prevent; regenerative; response; scaffold

Millions of American go through total knee replacement every year due to osteoarthritis. Surgical treatment of this disease is to implant replacement auto or allografts. Despite many advantages, these grafts poses several limitations including limit of supplies, donor site morbidity (for autografts) and immune response (in case of allografts). Consequently, engineered grafts - constructed in vitro by culturing autologous chondrocytes on synthetic biomaterial scaffolds – have received attentions. Yet, they also exhibit issues, one of which is the inefficiency of seeded-chondrocytes in these grafts to generate hyaline cartilages after implantation, preventing their widespread use. As such, we believe it is necessary to seek for a new approach to effectively stimulate and accelerate cartilage growth from commonly-used chondrocyte-seeded grafts, enhancing the grafts’ healing and regeneration capability. Electrical stimulation (ES) have been shown to exhibit profound effects on cartilage and bone repair/regeneration. However, current ES devices present many drawbacks including inefficiency of generated electrical field (for external ES devices), bulky size and toxic materials used in electrical stimulators, and non- degradability of implanted ES devices. Piezoelectric materials, which can generate electrical signals from deformation and vice versa, can be employed to create self-powered electrical stimulators. Interestingly, Poly-L-Lactid acid (PLLA), a biodegradable polymer which has been used in many medical implants, can exhibit piezoelectricity when being processed properly. Although not having a high piezoelectric constant, PLLA, owing to its low dielectric parameter, exhibits the same efficiency for energy conversion as the common Polyvinylidene fluoride (PVDF) polymer. In this project, we study the science and technology to create a biodegradable, highly efficient piezoelectric PLLA stimulator and integrate the stimulator with a biological chondrocyte-seeded cartilage graft, forming a bionic cartilage tissue. Hypothetically, this bionic cartilage will create a feedback loop in which more damaging joint-forces imparted on the cartilage would generate more useful electricity, which in turn enhances cartilage growth. Once less force is exerted on the implant, the graft will be subject to less electrical stimulation, avoiding harmful overdosing effect of electrical current on cartilage cells. The generated electrical outputs – in response to joint force - can be tailored and optimized by altering PLLA film’s properties (e.g. thickness, molecular weight, piezoelectric efficiency and number of PLLA layers etc.). As such, this “smart” bionic cartilage will offer an innovative approach, optimizing electric stimulation for cartilage repair and regeneration from autologous chondrocyte-seeded grafts.

每年有数百万美国人因骨关节炎接受全膝关节置换术。外科手术 本病的治疗方法是植入替代的自体或同种异体骨。尽管有许多优点，这些移植物 造成了几个限制，包括供应限制、供体部位发病率(自体移植)和免疫反应 (如属同种异体移植)。因此，工程移植物--通过培养自体细胞在体外构建 软骨细胞在合成生物材料支架上的应用受到了人们的关注。然而，它们也展示了一些问题，其中之一 这就是这些移植物中的种子软骨细胞在植入后生成透明软骨的效率低下， 阻止了它们的广泛使用。因此，我们认为有必要寻求一种新的方法来有效地 从常用的软骨细胞种子移植物中刺激和加速软骨生长，增强移植物的 治疗和再生能力。 电刺激(ES)已被证明对软骨和骨骼有深远的影响 修复/再生。然而，目前的ES设备存在许多缺点，包括生成效率低下 电刺激器中使用的电场(用于外部ES设备)、体积大小和有毒材料，以及非 植入ES装置的降解性。 压电材料可以通过变形产生电信号，反之亦然。 被用来制造自给式电刺激器。有趣的是，聚L丙交酸(PLLA)，一种可生物降解的 聚合物已用于许多医疗植入物，在加工过程中会表现出压电性。 恰到好处。尽管PLLA不具有很高的压电常数，但由于其介电参数较低，因此表现出 与普通聚偏氟乙烯(PVDF)聚合物具有相同的能量转换效率。 在这个项目中，我们研究了科学技术来创造一种可生物降解的、高效的 并将该刺激器与生物软骨细胞种子软骨移植整合在一起， 形成仿生软骨组织。假设，这种仿生软骨将创造一个反馈循环，在这个循环中， 对软骨造成破坏的关节力会产生更多有用的电能，进而增强 软骨生长。一旦对植入物施加较小的力，移植物就会受到较少的电刺激， 避免电流过量对软骨细胞的有害影响。产生的电气输出-输入 对连接力的响应-可以通过改变PLLA膜的属性(例如，厚度， 相对分子质量、压电效率和PLLA层数等)。因此，这种“智能”的仿生软骨 将提供一种创新的方法，优化电刺激，以修复和再生软骨 自体软骨细胞种植移植物。