Customizable Fabrication of Photothermal Microneedles with Plasmonic Nanoparticles Using Low-Cost Stereolithography Three-Dimensional Printing

Abstract

Photothermal microneedle (MN) arrays have the potential to improve the treatment of various skin conditions such as bacterial skin infections. However, the fabrication of photothermal MN arrays relies on time-consuming and potentially expensive microfabrication and molding techniques, which limits their size and translation to clinical application. Furthermore, the traditional mold-and-casting method is often limited in terms of the size customizability of the photothermal array. To overcome these challenges, we fabricated photothermal MN arrays directly via 3D-printing using plasmonic Ag/SiO₂ (2 wt % SiO₂) nanoaggregates dispersed in ultraviolet photocurable resin on a commercial low-cost liquid crystal display stereolithography printer. We successfully printed MN arrays in a single print with a translucent, nanoparticle-free support layer and photothermal MNs incorporating plasmonic nanoaggregates in a selective fashion. The photothermal MN arrays showed sufficient mechanical strength and heating efficiency to increase the intradermal temperature to clinically relevant temperatures. Finally, we explored the potential of photothermal MN arrays to improve antibacterial therapy by killing two bacterial species commonly found in skin infections. To the best of our knowledge, this is the first time describing the printing of photothermal MNs in a single step. The process introduced here allows for the translatable fabrication of photothermal MN arrays with customizable dimensions that can be applied to the treatment of various skin conditions such as bacterial infections.

Keywords: Ag; antibacterial; flame spray pyrolysis; plasmonic coupling; silver nanoaggregates; skin infections.

Figure 1

(a) Schematic illustration of the two-step 3D-printing of photothermal MN arrays by (i) uploading a customizable MN array design to an LCD–based SLA 3D-printer, (ii) printing the MN arrays in a two-step process in which the array support is printed using clear UV resin and the needles using a plasmonic Ag/SiO₂ (2 wt % SiO₂) NP-filled UV resin, and (iii) postcuring the MN array under UV light for 10 min. (b–e) Digital images of 3D-printed photothermal MNs arrays with various shapes (b,c), using a bendable, biocompatible support (d), and in comparison to a Ag/SiO₂ NP-free MN array (e). (f) SEM image of single 3D-printed photothermal MN, red arrow indicating high-density elements such as Ag on the surface of the MN.

Figure 2

Influence of mixing methodology on Ag/SiO₂ (2 wt % SiO₂) NP dispersion in printing resin. Bright-field and SEM images for cured resin droplets with Ag/SiO₂ NPs dispersed by (a–c) vortexing, (d–f) vortexing and ultrasonication, or (g–i) vortexing, ultrasonication, and bead homogenization. SEM-based agglomerate size distributions from 0–40 (j) and (k) 10–100 μm sizes with corresponding mean and standard deviation of the Feret diameter, bars plotted overlapping and partially transparent causing mixed coloration, N > 1000. (l) Photothermal response of MNs under NIR irradiation at 808 nm at 1 W cm^–2 printed with Ag/SiO₂ NP resin dispersed by vortexing and sonication or additional homogenization, n = 3.

Figure 3

Height reduction of Ag/SiO₂ (2 wt % SiO₂) NP-loaded 3D-printed MN arrays after compression at 32 N for 30 s. Bright-field microscopy images of side-view of MN arrays for three height to base ratios (3:1.2, 4:1.2, and 5:1.2) before (a) and after (b) compression at Ag/SiO₂ NP concentration of 5 mg g^–1. Quantitative measurement of needle height reduction for (c) different dimensions of MN and (d) for various Ag/SiO₂ NP loadings in resin for MN arrays at 4:1.2 height to base ratio. Data is shown as mean ± SD, n = 3.

Figure 4

In air photothermal heating of 3D-printed Ag/SiO₂ (2 wt % SiO₂) MN arrays under laser irradiation at 808 nm at 1 W cm^–2. (a) Average temperature increase of 10 × 10 pixels center point of MN arrays over time produced with different needle height to width ratios and (b) with varying Ag/SiO₂ NP concentrations in the resin. (c) Maximum reached temperature increase (ΔT) of MN arrays as a function of the laser intensity. (d) Repeated heating of MN arrays with H/W ratio of 4:1.2 and Ag/SiO₂ NP concentration of 5 mg g^–1 after disinfection in EtOH. Data shown as mean ± SD, n = 3.

Figure 5

Skin insertion and in-skin hyperthermia of 3D-printed MN arrays. (a) Illustration of experimental setup to study in-skin hyperthermia from MN application under NIR. Microscopy images at (b) 5× and (c) 10× magnification of cross-section of porcine skin after MN array application. (d) In-skin hyperthermia over time under laser light irradiation at 808 nm at 0.5 W cm^–2 by 3D-printed MN arrays produced with varying NP concentration in the resin. (e) Maximum temperature increase in the dermis as a function of the NP concentration in the resin. (f) Illustration of measurement points obtained from the thermal images of the IR camera at the center (C), middle (M), and edge (E) or from a thermocouple on the top epidermal or bottom dermal side of the skin sample. (g) Maximum temperature increase at the various measurement points across the skin sample. Data shown as mean ± SD, n = 3.

Figure 6

Antibacterial activity of photothermal 3D-printed MN arrays. (a) Schematic of experimental setup for evaluation of temperature profile and antibacterial effect of MN arrays in planktonic bacteria under NIR irradiation at 808 nm at 1 W cm^–2. Top-view image of serial dilution on agar of (b) S. aureus and (c) P. aeruginosa for treatment with and without MN arrays and varying durations of laser irradiation (0, 2, 5, 10 min). (d) Bacteria quantification (CFU mL^–1) of S. aureus (green circles) and P. aeruginosa (blue triangles) after continuous NIR irradiation and corresponding final temperature (right axis, red squares, n = 6). Data shown as mean and SD, n = 3.