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

摘要 手术植入/移植造成的慢性和无法愈合的手术伤口和感染仍然是 严重的医疗问题。纳米纤维垫子似乎是一个吸引人的伤口敷料和 组织支架。具有大比表面积和高孔隙率的纳米材料可以同时 使有效止血、对渗出物的高吸收能力和气体渗透性以及优秀的 细胞和水分的滞留。此外，纳米纤维膜的柔韧性允许共形界面 创面呈曲线状。事实上，聚己内酯(PCL)、聚L-丙交酯(PLLA)和聚乳酸(PLLA)的纳米纤维垫 聚乳酸-羟基乙酸共聚物(PLGA)已用于伤口愈合，尽管这些可生物降解的支架 仍能为大伤患者提供适度的治愈率。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。由超声波产生的压电电荷已经被 证明能显著抑制细菌活性。我们的母公司R21赠款(R21AR078744)旨在开发 一种可植入膝关节的传感器/软骨-移植物一体化系统，测量关节受力 应用于软骨上，同时修复软骨缺损处。传感器/组织杂交是 基于我们最近开发的可生物降解的压电PLLA纳米纤维构建，并设计为 通过手术植入到缺损处。这种传感器/移植物移植方法的一个重要问题 在父母的资助中，植入过程容易感染，对软骨造成更大的损害 接受治疗。尽管灭菌，细菌通常存在于组织支架或医疗植入设备中 在体外构建的。在这方面，我们在父母赠款中建议的传感器是由特殊的压电式PLLA制成的 超声波作用下可产生可控表面电荷的纳米纤维(US) 产生能杀死细菌的活性氧化物种(ROS)。因此，该传感器可用于 同时作为产生ROS的仓库或抗菌伤口敷料，可以在 移植过程。为了实现这一目标，我们需要了解机制并展示 聚乳酸可生物降解纳米纤维创面敷料垫体内抗菌效果。因此，在这方面， 补充助学金，我们的少数民族博士生I‘jaad Muhammad将进行抗菌研究 聚乳酸创面敷料垫的作用机理。他将得到PI(阮氏)的直接支持和监督 以及共同导师(Cato Laurencin博士)，他也是父母赠款中的一名共同导师。这项研究将非常重要 给学生，奠定了坚实的基础，为他获得博士学位的主题，智能生物降解 用于医疗植入设备和组织再生工程的聚合物“，并从事长期职业生涯 学术界的目标是成为生物材料领域的领先研究人员

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