Real-time Measurement of Joint-loading for Osteoarthritis Study and Treatment R21AR078744

用于骨关节炎研究和治疗的关节负荷实时测量 R21AR078744

• 批准号: 10362159
• 负责人: Thanh Nguyen
• 金额: $ 4.03万
• 依托单位: UNIVERSITY OF CONNECTICUT STORRS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10362159
• 关键词: Academia; Acoustics; Anti-Bacterial Agents; Bacteria; Biocompatible Materials; Cartilage; Cells; Charge; Chronic; Defect; Degenerative polyarthritis; Deposition; Doctor of Philosophy; Electricity; Exudate; Foundations; Gases; Glycolates; Goals; Grant; Hemostatic function; Implant; In Vitro; Infection; Injury; Joints; Knee joint; Measures; Mechanics; Medical; Medicine; Membrane; Mentors; Minority; Operative Surgical Procedures; Parents; Permeability; Porosity; Process; Property; Regenerative engineering; Research Personnel; Site; Sonication; Sterilization; Students; Supervision; Surface; Surgical Wound Infection; Systems Integration; Time; Tissue Grafts; Tissues; Transplantation; Ultrasonography; base; biodegradable polymer; career; cartilage transplantation; design; doctoral student; flexibility; force sensor; healing; implantable device; implantation; in vivo; joint loading; laurencin; medical implant; nanofiber; nanomaterials; parent grant; polycaprolactone; pressure; prevent; regenerative tissue; scaffold; sensor; temporal measurement; tissue support frame; tool; wound; wound dressing; wound healing

Abstract Chronic and non-healing surgical wounds and infection due to surgical implantation/transplantation remain a major medical problem. Nanofiber mats have appeared to be an appealing platform for wound dressings and tissue scaffolds. The nanomaterial with a large surface-to-volume ratio and high porosity can simultaneously enable an effective hemostasis, a high absorbability of exudate and gas permeability along with an excellent retention of cells and moisture. In addition, the flexibility of the nanofiber membrane allows a conformal interface with curvilinear wound surface. Indeed, nanofiber mats of Polycaprolactone (PCL), Poly-L-Lactide (PLLA), and Polylactic-co-glycolic acid (PLGA) have been used for wound healing although these biodegradable scaffolds still provide modest healing rates in large injuries. Piezoelectric effect is an ability of some materials to convert mechanical deformation into electricity and vice versa. Piezoelectric charge, generated by sonication, has been demonstrated to significantly suppress bacterial activities. Our parent R21 grant (R21AR078744) aims to develop a sensor/cartilage-graft integration system which can be implanted into the knee joint, measure the joint force applied on the cartilage, and at the same time, heal the cartilage defect. The sensor/tissue hybridization is constructed, based on our recently developed biodegradable piezoelectric PLLA nanofibers, and designed to be surgically implanted into the defect site. One significant problem for such a sensor/graft transplantation approach in the parent grant is that the implantation process is prone to infection, causing more damages on the cartilages to be treated. Despite sterilization, bacteria are often present in tissue scaffolds or medical implanted devices constructed in vitro. In this regard, our proposed sensor in the parent grant is made of special piezoelectric PLLA nanofibers which can generate controllable surface charge under applied acoustic pressure of ultrasound (US) to produce reactive oxidative species (ROS) which can kill off bacteria. The sensor can be therefore used at the same time to be a ROS-producing depot or an antibacterial wound dressing which can kill bacteria after the transplantation process. To achieve such a goal, we need to understand the mechanism and demonstrate the antibacterial effect of the PLLA biodegradable nanofiber wound-dressing mat in vivo. Accordingly, in this supplementary grant, our minority PhD student, I’jaad Muhammad, will perform the studies on antibacterial mechanism of the PLLA wound dressing mat. He will receive a direct support and supervision of the PI (Nguyen) and the co-mentor (Dr. Cato Laurencin) who is also a co-I in the parent grant. The study will be very important to the student, laying a strong foundation for him to achieve his PhD degree in the topic of “smart biodegradable polymers for medical implanted devices and tissue regenerative engineering” and pursue his long-term career goal in academia to become a leading researcher in the field of biomaterials

摘要 由于手术植入/移植引起的慢性和不愈合的手术伤口和感染仍然是一个严重的问题。 严重的医疗问题。纳米纤维垫似乎是用于伤口敷料的有吸引力的平台， 组织支架具有大的表面积体积比和高孔隙率的纳米材料可以同时 能够有效止血，渗出物的高吸收性和气体渗透性沿着， 保持细胞和水分。此外，该膜的柔性允许共形界面 伤口表面呈曲线形事实上，聚己内酯（PCL）、聚左旋丙交酯（PLLA）和聚己内酯（PLLA）的纳米纤维垫 聚乳酸-共-乙醇酸（PLGA）已用于伤口愈合，尽管这些可生物降解的支架 在大面积损伤中仍然提供适度的愈合率。压电效应是某些材料的一种转换能力， 机械变形转化为电能，反之亦然。由超声处理产生的压电电荷已经被 证明其显著抑制细菌活性。我们的母公司R21赠款（R21 AR 078744）旨在开发 传感器/软骨移植物集成系统，其可植入膝关节中，测量关节力， 贴敷在软骨上，同时修复软骨缺损。传感器/组织杂交是 构建，基于我们最近开发的可生物降解的压电PLLA纳米纤维， 通过手术植入缺损部位这种传感器/移植物移植方法的一个重要问题是 植入过程容易感染，对软骨造成更多损伤 接受治疗尽管进行了灭菌，但细菌通常存在于组织支架或医疗植入装置中 在体外构建。在这方面，我们提出的传感器在家长赠款是由特殊的压电PLLA 在施加超声声压下可产生可控表面电荷的纳米纤维（US） 产生活性氧化物质（ROS），可以杀死细菌。因此，传感器可用于 同时作为ROS生产仓库或抗菌伤口敷料，可以在伤口愈合后杀死细菌。 移植过程为了实现这一目标，我们需要了解机制，并展示 PLLA可生物降解敷料垫的体内抗菌效果。因此，在此 我们的少数民族博士生I 'jaad Muhammad将获得补充拨款，进行抗菌研究 PLLA伤口敷料垫的机制。他将得到PI（Nguyen）的直接支持和监督 和共同导师（卡托劳伦辛博士）谁也是一个共同的我在家长补助金。这项研究将非常重要 为他在“智能生物降解”课题上获得博士学位奠定了坚实的基础 用于医疗植入设备和组织再生工程的聚合物”，并追求他的长期职业生涯 在学术界的目标是成为一个领先的研究人员在生物材料领域