3D Printing of Antibacterial Polymer Devices Based on Nitric Oxide Release from Embedded S-Nitrosothiol Crystals

ACS Applied Bio Materials 2021 Volume 4, Issue 10, Pages 7653–7662

Controlled release of drugs from medical implants is an effective approach to reducing foreign body reactions and infections. We report here on a one-step 3D printing strategy to create drug-eluting polymer devices with a drug-loaded bulk and a drug-free coating. The spontaneously formed drug-free coating dramatically reduces the surface roughness of the implantable devices and serves as a protective layer to suppress the burst release of drugs. A high viscosity liquid silicone that can be extruded based on its shear-thinning property and quickly vulcanize upon exposure to ambient moisture is used as the ink for 3D printing. S-Nitrosothiol type nitric oxide (NO) donors in their crystalline forms are selected as model drugs because of the potent antimicrobial, antithrombotic, and anti-inflammatory properties of NO. Direct ink writing of the homogenized polymer-drug mixtures generates rough and ill-defined device surfaces because of the exposed S-nitrosothiol microparticles. When a low-viscosity silicone (polydimethylsiloxane) is added into the ink, this silicone diffuses outward upon deposition to form a drug-free outermost layer without compromising the integrity of the printed structures. S-Nitrosoglutathione (GSNO) or S-nitroso-N-acetylpenicillamine (SNAP) embedded in the printed silicone matrix releases NO under physiological conditions from days to about one month. The microsized drug crystals are well-preserved in the ink preparation and printing processes, which is one reason for the sustained NO release. Biofilm and cytotoxicity experiments confirmed the antibacterial property and safety of the printed NO-releasing devices. This additive manufacturing platform does not require dissolution of drugs and involves no thermal or UV processes and, therefore, offers unique opportunities to produce drug-eluting silicone devices in a customized manner.