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

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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