Controlled NO-Release from 3D-Printed Small-Diameter Vascular Grafts Prevents Platelet Activation and Bacterial Infectivity

Abstract

Thrombogenicity and bacterial infectiveness are the most common complications for foreign blood contacting surfaces associated with functional failure of small-diameter vascular grafts (SDVGs). In this work, novel bactericidal and nonthrombogenic SDVGs were manufactured via 3Dprinting technology, thus producing a controlled nitric oxide (NO) release coating. S-Nitroso-N-acetyl-D-penicillamine (SNAP) was synthesized as an NO-donor, and three biomedical grade composite matrixes of poly(ethylene glycol) (PEG)-SNAP, polycaprolactone (PCL)-SNAP, and PEG-PCL-SNAP were validated for water uptake and NO-release kinetics. To optimize and extend the NO releasing profile, a PCL topcoat (tc) was deposited over the NO-releasing layer. The PEG-PCL-SNAP-tc was selected for biological tests as its NO-release profile was prolonged and well-controlled. Coating the 3D-printed SDVG with PEG-PCL-SNAP-tc resulted in quantitative antibacterial features against both Gram-positive and Gram-negative bacteria and in NO-mediated inhibition of platelet activation and aggregation. Antibacterial and antithrombogenic properties in plasma are expected to be as effective as in PBS, since NO release in plasma was not significantly different from that in PBS. Overall, application of the inexpensive, rapid, and reproducible 3D-printing technology as a custom-based production method, in combination with a well-controlled NO release system, is promising for the production of innovative bactericidal and hemocompatible SDVGs.

Additively manufactured small‐diameter vascular grafts with improved tissue healing using a novel SNAP impregnation method

“…The antibacterial effect of controlled NO delivery in this study is in agreement with earlier reports where NO‐releasing significantly killed both S. aureus (Lee et al, ; Mihu et al, ; Seabra et al, ) and E. coli (Kabirian, Ditkowski, et al, ; Lee et al, ). The advantage of the antibacterial properties of the NO controlled release system is that it does not cause the development of bacterial resistance due to its multiple nonspecific bactericidal mechanisms (Backlund, Worley, & Schoenfisch, ).…”

“…The SDVGs were successfully prepared from PLA filament using a FDM 3D printer according to a predesigned CAD model. Previously, we fabricated biodegradable 3D‐printed SDVGs from PLA using the FDM machine (Kabirian et al, ; Kabirian, Ditkowski, et al, ; Kabirian, Milan, et al, ). In this study, to improve the healing and antibacterial properties of such SDVGs, a novel NO‐releasing system was successfully incorporated.…”

“…3D printing is an advantageous procedure to design and fabricate highly accurate and reproducible custom‐based structures which can promisingly be used for cardiovascular tissue engineering applications (Kabirian, Ditkowski, et al, ; Kabirian, Milan, et al, ). In the current study, SDVGs were successfully fabricated using the FDM 3D printing technology with PLA filaments (Figure a).…”

“…A modified version of the SNAP synthesis protocol was used in this study (Kabirian, Ditkowski, et al, ). Briefly, 1,000 mg of NAP was dissolved in 25 mL of methanol and consequently 15 mL of 1 M HCl, 500 μL of H 2 SO 4 (98%), and 724.5 mg of NaNO 2 were added and mixed, respectively.…”

Engineered 3D Polymer and Hydrogel Microenvironments for Cell Culture Applications

“…Although PEG does not encourage cell adhesion, it represents a very good candidate for the encapsulation of other bioactive materials, drugs, and chemicals. Recently it has been reported how a combination of S-nitroso-N-acetyl-D-penicillamine and PEG-PCL was coated on a 3D printed PLA scaffold for the controlled release of nitric oxide and the realization of antibacterial and blood-compatible vascular grafts [183]. Similarly, PEG norbornene microspheres encapsulated cells for controlled cell delivery and release [182], while curcumin, an antioxidant and anti-inflammatory, was encapsulated in PCL-PEG-PLGA which together was loaded into a hydroxyapatite matrix [184].…”