Multi-functional 3D Printed Dental Implants for Preventing Peri-implantitis - Project Summary/Abstract Peri-implantitis is one of the most common and challenging implant-related oral infections that affect millions of patients every year. This project aims to develop a multi-functional [antibacterial and bioactive (that can osseointegrate efficiently)] patient-specific dental implant that can effectively prevent peri-implantitis. Specifically, we will develop highly tunable silver-doped amorphous magnesium phosphate (AgAMP) bioceramic particles and incorporate them in a high-performance biopolymer matrix known as Polyetheretherketone (PEEK) to engineer AgAMP-PEEK multi-functional composite, referred to as Ultra-PEEK. Notably, Ultra-PEEK will be developed as uniform diameter filaments that can be used in a Fused Filament Fabrication (FFF)-based 3D printer as a feedstock material to develop high-resolution implants. Feasibility studies show that the 3D-printed Ultra-PEEK implants exhibit approving mechanical properties, and the Ultra-PEEK implant composition demonstrates comparable osseointegration properties to clinical standard Titanium implants. Notably, Ultra- PEEK implants also show promising in vitro antibacterial efficacy. However, refining the implant composition and 3D printing parameters is necessary to yield implants with optimum mechanical, antibacterial, and osseointegration properties (i.e., with high clinical value). Hence, in the first specific aim, we aim to determine the processing-structure-property relationships of 3D-printed Ultra-PEEK implants. To accomplish the latter aim, we will analyze the effect of AgAMP content on Ultra-PEEK’s mechanical properties. We will develop 3D-printed Ultra-PEEK implants with varying AgAMP content using high-temperature FFF and validate their fatigue strength per FDA requirements. In the second specific aim, we will determine the infection resistance and osseointegration properties of Ultra-PEEK implants. The bacterial inhibition capabilities will be initially determined in vitro using biofilm models against peri-implantitis-associated oral pathogens. Biocompatibility will be determined using standard in vitro assays. Finally, a well-proven polymicrobial peri-implantitis rodent (rat) model will be used to determine Ultra-PEEKs’ infection resistance and osseointegration capabilities. Finally, in the third specific aim, a highly translational peri-implantitis porcine animal model will be used to determine the implants' infection resistance and osseointegration capabilities by analyzing clinical parameters such as bleeding on probing, pocket depth, gingival recession, and clinical attachment level compared to titanium controls. After accomplishing this project, we envision establishing the first-of-its-kind, unique, antibacterial, and bioactive 3D printed implant that will hinder peri-implantitis incidences for patients needing tooth implants and relieve patients from the baleful aftermaths of implant-related infections.