Effect of temperature and ultraviolet light on the bacterial kill effectiveness of antibiotic-infused 3D printed implants.

Drug eluting 3D printed polymeric implants have great potential in orthopaedic applications since they are relatively inexpensive and can be designed to be patient specific thereby providing quality care. Fused Deposition Modeling (FDM) and Stereolithography (SLA) are among the most popular techniques available to print such polymeric implants. These techniques facilitate introducing antibiotics into the material at microscales during the manufacturing stage and subsequently, the printed implants can be engineered to release drugs in a controlled manner. However, FDM uses high temperature to melt the filament as it passes through the nozzle and SLA relies on exposure to nanoscale wavelength ultraviolet (UV) light which can adversely affect the anti-bacterial effectiveness of the antibiotics. The focus of this article is two-fold: i) Examine the effect of high temperature on the bacterial kill-effectiveness of eluted antibiotics through Polycaprolactone (PCL) based femoral implants and ii) Examine the effect of exposure to ultraviolet (UV) light on the bacterial kill-effectiveness of eluted antibiotics through femoral implants made up of a composite resin with various weight fractions of Polyethylene Glycol (PEG) and Polyethylene Glycol Diacrylate (PEGDA). Results indicate that even after exposing doxycycline, vancomycin and cefazolin at different temperatures between 20oC and 230oC, the antibiotics did not lose their effectiveness (kill radius of at least 0.85 cm). For doxycycline infused implants exposed to UV light, it was seen that a resin with 20 % PEGDA and 80 % PEG had the highest efficacy (1.8 cm of kill radius) and the lowest efficacy was found in an implant with 100 % PEGDA (1.2 cm of kill radius).

Efficacy of eluted antibiotics through 3D printed femoral implants.

Costs associated with musculoskeletal diseases in the United States account for 5.7% of the Gross Domestic Product (GDP) (Weinstein et al. 2018). As such, there is a need to pursue new ideas in orthopaedic implants that can decrease cost and improve patient care. In the recent years, 3D printing of polymers using Fused Deposition Modeling (FDM) and metals using Direct Metal Laser Sintering (DMLS) has opened several exciting possibilities to create customized orthopaedic implants. Such implants can be engineered to release antibiotics in a controlled manner by infusing the drug into the material during manufacturing stage. However, the prevalence of high temperature could impact the anti-bacterial effectiveness of the eluted antibiotics in such implants. An alternative approach to circumvent this issue would be to modify the implant geometry to incorporate built-in design features such as micro-channels and reservoirs in which antibiotics can be introduced prior to the surgical procedure. Irrespective of the approach used, the ability of 3D printed orthopaedic implants to elute antibiotics, and the rate of elution are not well understood. The purpose of this article is to study the elution of doxycycline through 3D printed femoral implants using three different materials: Poly-Lactic Acid (PLA), Poly-Caprolactone (PCL) and Titanium grade Ti-6Al-4V. The PLA and Ti-6Al-4V implants were designed with built-in reservoirs and micro-channels in which doxycycline was introduced post the manufacturing stage. However, the PCL implants were printed from a PCL spool that was infused with doxycycline using an extruder. The PLA and Ti-6Al-4V experiments were run for a period of 31 days and the PCL experiment for one day. The antibacterial ability of eluted doxycycline from all implants were examined using Kirby-Bauer test on the bacteria E.coli k-12. The results show that most of doxycycline eluted through the three materials in the first 24 hours. After the initial spike, a steady release was achieved for the PLA and Ti-6Al-4V implants for 30 days. During this timeframe, Ti-6Al-4V implants released more doxycycline than the PLA implant. The eluted antibiotics through all the implants demonstrated the ability to kill bacteria in the subsequent Kirby-Bauer test. These outcomes show that irrespective of how the antibiotics were introduced, 3D printed polymeric and metallic implants have great potential in orthopaedic applications.