Antimicrobial Polymers for Additive Manufacturing

Abstract

Three-dimensional (3D) printing technologies can be widely used for producing detailed geometries based on individual and particular demands. Some applications are related to the production of personalized devices, implants (orthopedic and dental), drug dosage forms (antibacterial, immunosuppressive, anti-inflammatory, etc.), or 3D implants that contain active pharmaceutical treatments, which favor cellular proliferation and tissue regeneration. This review is focused on the generation of 3D printed polymer-based objects that present antibacterial properties. Two main different alternatives of obtaining these 3D printed objects are fully described, which employ different polymer sources. The first one uses natural polymers that, in some cases, already exhibit intrinsic antibacterial capacities. The second alternative involves the use of synthetic polymers, and thus takes advantage of polymers with antimicrobial functional groups, as well as alternative strategies based on the modification of the surface of polymers or the elaboration of composite materials through adding certain antibacterial agents or incorporating different drugs into the polymeric matrix.

Keywords: 3D printing; additive manufacturing; antibacterial polymers; biocompatible systems; drug delivery systems.

Figure 1

Steps involved in the fabrication of a cup by additive manufacturing (AM). Reproduced with permission from Ref. [1].

Figure 2

AM timeline for different applications. Reproduced with permission from Ref. [14].

Figure 3

Chemical structures and microbiological applications of several zwitterionic polymers and their derivatives. Reproduced with permission from Ref. [75].

Figure 4

Illustrative scheme of the reversible lactonization that enables the system to kill bacteria (cationic state) and the release of inactivated bacterial cells occurring upon ring-opening and formation of the zwitterionic state. Reproduced with permission from Ref. [75].

Figure 5

(a) Schematic description of the three-dimensional (3D) printing process using cellulose acetate (CA) dissolved in acetone. (b) Photograph of a close-up of printing tip during the manufacturing process. (c) Micrographs that show the acetone evaporating process. 3D printed parts, (d) eyeglass frames, and (e) a rose. Reproduced with permission from Ref. [92].

Figure 6

(a) Evaluation of the antimicrobial performance of the 3D printed CA parts, in which the viable bacteria count was normalized with the PL- results; and (b) Images of the bacteria cultured Petri dishes exposed to different conditions. Adapted with permission from Ref. [92].

Figure 7

(a) In vitro cytotoxicity test of Nanofibrillated cellulose (NFC) bioink. Human nasal chondrocytes (hNC) and rabbit auricular chondrocytes (rAC) were used as indicator cells to determine the cytotoxic effects potentially caused by bioink components, cross-linking, or the bioprinting process. (b) 3D bioprinting process of chondrocyte-laden NFC-A auricular construct with open porosity. (c) 3D bioprinted auricular and (d) lattice-structured constructs, laden with hNCs, after 28 days of culture. Reproduced with permission from Ref. [93].

Figure 8

(a) 3D printed dental parts using diurethanedimethacrylate/glycerol dimethacrylate (UDMA/GDMA) composites. (b) Uniaxial tensile tests of 14 mol% UDMA/GDMA with the modified methacrylate monomers with an alkyl chain length of n = 12 (QA_C₁₂). (c) Comparison of the contact-killing efficacy of 3D printed UDMA/GDMA and UDMA/GDMA/QA_C₁₂ and (d) comparison of the long-term contact-killing efficacy of 3D printed UDMA/GDMA and UDMA/GDMA/QA_C₁₂ six days after live/dead staining. Reproduced with permission from Ref. [94].

Figure 9

Above Schematic representation of the synthesis and grafting process of the 3D printed parts. Below (a) Photographs of the inhibition tests performed after 24 hours of bacteria growth, (b) the control sample and (c) 3-sulfopropyl methacrylate potassium salt (SPMA)-treated sample. Similar results after 48 hours for the (d) control and (e) SPMA-treated sample. Reproduced with permission from Ref. [5].

Figure 10

Left: Lateral and top 3D views of the micro-computed topography (µ-CT) images of the fabricated parts. Right: Bacterial viability on the different hydrogels with a variable amount of acrylic acid (AA). (a,b) 25 wt% AA, (c,d) 20 wt% AA, and (e,f) 10 wt% AA. Green fluorescence corresponds to the emission of all the bacteria, while the red one is related to the emission of propidium iodide (dead bacteria). Reproduced with permission from Ref. [95].

Figure 11

(a) Extrudated and 3D-printed and (b) SEM images of extrudated and 3D-printed geometries. Reproduced with permission from Ref. [96].

Figure 12

A. Gentamicin sulfate (GS)-doped poly(lactic acid) (PLA) and poly(methyl methacrylate) (PMMA) filaments. (A) 2.5 wt% gentamicin PLA filament; (B) Control PLA filament; (C) Control PMMA filament; (D) 2.5 wt% gentamicin PMMA filament. B. (a–c) 1 wt% gentamicin PLA filament; (d) 1 wt% gentamicin PMMA filament. Reproduced with permission from Ref. [97].

Figure 13

(a) Schematic description of the electrohydrodynamic (EHD) technique. SEM images of drug-loaded polycaprolactone (PCL)/polyvinyl pyrrolidone (PVP) patches at selected time intervals for the in vitro release study. (b) At 30 min; (c) At 60 min; and (d) At 90 min. Reproduced with permission from Ref. [42].

Figure 14

Left: 3D CAD model of scaffold selected for the fabrication by fused deposition modeling (FDM). Middle: SEM images of the scaffold surface revealing the layered structure obtained via FDM but also the formation of micropores. Right: Effect of the chemical composition on the antimicrobial properties of the 3D printed part. Above, without the antimicrobial functional group, and below, with the antimicrobial functional group. Reproduced with permission from Ref. [99].

Figure 15

(a) Schematic description of FDM filament formation. Also, images of thermoplastic polyurethane (TPU)/poly(lactic acid) (PLA)/graphene oxide (GO) printed parts are shown. Green fluorescence images of cellular live/dead tests of the samples with different GO loads: (b) 0.5 wt%; (c) 2 wt%; and (d) 5 wt%. Reproduced with permission from Ref. [100].

Figure 16

(a) Metal-loaded filaments and (b) 3D scan of a nose to create a designed wound dressing. Reproduced with permission from Ref. [87].

Figure 17

The protocol used to fabricate a complete denture, using the SLA printing technique. (a) Design in software. (b) Final construction in the 3D printer platform. (c) Denture cleaning with isopropanol. (d) Denture drying and supports removal. (e) Prototype denture polished. (f) Final post-curing procedure. (g) Esthetic adjustment. Reproduced with permission from Ref. [103].

Figure 18

(A) Research participant with an index finger amputation. (B) 3D printer finder prothesis using PLACTIVE^TM antibacterial 3D filament. (C) Patient using the antibacterial 3D finger prosthesis; and (D) Patient performing the Box and Block Test. Reproduced with permission from Ref. [102].