Joint replacement surgeries are the most common orthopedic procedures with over 1 million total hip and knee replacement surgeries performed every year in the United States [1]. Postoperative events such as bone loss, device loosening, breakage and adverse immune reactions to foreign substances are observed, leading to severe pain, inflammation, and even implant rejection. To overcome these adverse events and enhance osteointegration, medical devices made up of stainless steel have been widely used in orthopedic applications. Even though traditional manufacturing of orthopedic implants is less expensive and takes less time, the fixed dimensions of standard implants are not the best fit for host bones and thus might lead to adverse immune reactions [2].  In order to address these issues, additive manufacturing of complex geometrical implants with desired porosity and roughness have been designed to facilitate osteointegration and to provide long-term fixation of the implant [2]. Moreover, accumulation of reactive oxygen species at the implant site leads to alteration of signaling pathways and thus results in poor osteointegration [3]. In order to mitigate this problem, novel multilayer biomaterial coatings containing anti-inflammatory drug meloxicam has been deposited on the 3D printed stainless steel (316L), along with biodegradable polymer, poly (L-lactide-co-glycolide) (PLGA).

The drug content and content uniformity of coated metal implants was 100±5% indicating the uniformity of the coatings. The surface morphology of 3D printed implants revealed a smooth, uniform, and homogenous surface without any macroscopic defects. The average coating thickness was found to be around 449 µm. DSC thermogram of meloxicam/PLGA implant did not show any drug peak near to its melting point indicating the conversion of meloxicam from crystalline to amorphous state. The cumulative amount of drug release was found to be linearly proportional to the percentage of incorporated drug and inversely proportional to coating thickness. The implants with 1.5x and 2x coating thickness considerably extended the drug release for more than 30 days, confirming the capability of this approach to achieve sustained drug release for effective anti-inflammatory activity.  There is no significant effect of plasticizer on the cumulative release of meloxicam. Finally, cell adhesion studies showed that substantially more osteosarcoma cells were adhered to the implants with multilayer coatings than the uncoated implants. This might be due to the smoother surface of the multilayer coatings with decreased surface roughness compared to uncoated samples. The percentage cell viability for all the samples was found to be the same for both coated and control (glass slide) samples at 24h and 48h, indicating similar cytotoxicity. This implies that coating of drug and polymer on the metal surface has not affected the cell viability and the multilayer coating possessed excellent biocompatibility. Therefore, coating of meloxicam/PLGA on 3D printed stainless steel implants could possibly reduce the adverse drug reactions, promote tissue regeneration and could prevent implant rejections in orthopedic patients.

Keywords: 3D printed stainless steel, bone implants, meloxicam

References

1.  Steiner C, Andrews R, Barrett M, Weiss A. HCUP Projections: Mobility/Orthopedic Procedures 2003 to 2012. 2012. HCUP Projections Report # 2012-03. 2012 Sep 20. U.S. Agency for Healthcare Research and Quality.
2. Wong KC, Scheinemann P. Additive manufactured metallic implants for orthopaedic applications. Science China Materials. 2018 Apr 1;61(4):440-54.
3. Li X, Ma XY, Feng YF, Ma ZS, Wang J, Ma TC, Qi W, Lei W, Wang L. Osseointegration of chitosan coated porous titanium alloy implant by reactive oxygen species-mediated activation of the PI3K/AKT pathway under diabetic conditions. Biomaterials. 2015 Jan 1;36:44-54.