Iron-Oxide Nanoparticles Embedded in 3D-Printed PLA/HA Scaffolds for Magnetic Hyperthermia Therapy: An Experimental-Numerical Analysis of Thermal Behavior

Abstract

Hyperthermia is nowadays intensively investigated as a promising strategy to improve the therapeutic efficacy against different types of cancer and resistant infections. In particular, the remote generation of localized hyperthermia by magnetic field through iron-oxide nanoparticles (IONPs) offers good thermal conductivity in a controlled area. The incorporation of these IONPs in 3D-printed scaffolds designed for bone tissue regeneration has been scarcely addressed in the literature. This strategy would add the potential of magnetic-mediated hyperthermia against remnant cancer or resistant infections in the damaged tissue area to these personalized bone-related scaffolds. The present work proposes two methodologies to obtain 3D-printed bone-related scaffolds with magnetic properties: 1-Direct 3D printing with IONPs-embedded polylactic acid (PLA) and hydroxyapatite (HA), resulting in a uniform distribution of IONPs; and 2-Drop coating on 3D-printed PLA/HA scaffolds, resulting in the IONPs being concentrated on the scaffold surface. Physicochemical/mechanical characterizations were performed to confirm the IONPs' distributions and viability assays were carried out to validate the absence of cytotoxicity. Hyperthermia tests (314 kHz) were carried out, including the simulation/validation of the experimental equipment, to establish optimal distances from the planar coil. Temperature-time/distance curves were obtained and parametrized (R² > 0.96) for both methodologies in relation to the contribution of IONPs (0.20-1.00 mg), their distribution in the scaffold (uniform/concentrated), the electric-current intensity, and the distance. The results validated both methodologies to obtain personalized 3D-printed PLA/HA scaffolds with magnetic properties, reaching the required moderate/ablative hyperthermia levels.

Keywords: 3D-printed scaffolds; iron-oxide nanoparticles; magnetic hyperthermia; polylactic acid.

Figure 1

3D-FDM printer (a); extruder in detail (b); the samples’ design from the Simplify3D Professional Software (c); a sample of the scaffolds obtained by the 3D direct printing methodology (d) and by the drop coating of the IONPs on the already printed 3D PLA/HA scaffolds (e,f).

Figure 2

Alternating magnetic field generator and coupled used equipment.

Figure 3

A graphical representation of the magnetic flux lines induced by the coils (a); a simulation of the AMF modulus distribution along the symmetrical planes of the coils (b); the results of the numerical simulation of the AMF modulus intensity (c) and experimental values measured (d).

Figure 4

Stereomicroscope images of the 3D-printed scaffolds of PLA (a) and PLA/HA (3D0.00) (b) scaffolds obtained by 3D-printing methodology (c), specifically 3D0.40; and of the scaffolds obtained by the IONP drop coating on the 3D-printed PLA/HA scaffolds’ (d), the drop-coating methodology, specifically DC0.50.

Figure 5

The SEM micrographs and corresponding EDS spectra of scaffolds fabricated with both methodologies: (1) the 3D printing, namely with the sample 3D0.40 (a); and (2) the drop coating, with the sample DC0.50 (b).

Figure 6

FT-Raman spectra (a) of 3D-printed scaffolds with increasing contribution of IONPs from 0.20 to 1.00 mg/scaffold: 3D0.20, 3D0.40, and 3D1.00. FT-Raman spectrum obtained for 3D-printed PLA/HA scaffolds, free of IONPs, with 3D0.00 also included. The main characteristic bands of 3D-printed PLA are assigned, together with the main band of calcium phosphates (962 cm⁻¹) and the characteristic doublet assigned to the IONPs (represented by an asterisk). The amplified and deconvoluted doublet for the 3D1.00 scaffold is presented in (b). The quantitative evaluation of the FT-Raman spectra with the I530/I874 ratio obtained for the corresponding 3D-printed scaffolds (c).

Figure 7

Young’s modulus of the 3D printed scaffolds with increasing contributions of IONPs from 0.20 to 1.00 mg/scaffold: 3D0.20, 3D0.40, and 3D1.00. The bar plot represents mean ± standard error. The blue light color helps to visualize the similar values obtained for the three scaffolds evaluated.

Figure 8

Temperature–time measurements and curves of adjustment for 120 s after AMF exposure on the surface of the scaffolds obtained by (a) 3D printing: 3D0.20, 3D0.40, and 3D1.00, and (b) drop coating: DC0.25, DC0.50, and DC1.00 at 90 A, 314 kHz, and a coil distance of 9.60 mm.

Figure 9

Maximum temperature variation on the surface of the scaffolds obtained by (a) 3D printing: 3D0.20, 3D0.40, and 3D1.00, and (b) drop coating: DC0.25, DC0.50, and DC1.00 after AMF hyperthermia at different current intensities and a coil distance of 9.60 mm.

Figure 10

Temperature–distance curves measured after 120 s on the surface of the scaffolds obtained by (a) 3D printing: 3D0.20, 3D0.40, and 3D1.00 after AMF hyperthermia at 190 A, and (b) drop coating: DC0.25, DC0.50, and DC1.00 after AMF hyperthermia at 120 A.

Figure 11

Cell viability detected in osteoblast-like cells (MG63) in the presence of the extracts obtained from 3D-printed scaffolds with 0.40 mg in IONPs (3D0.40), compared to the positive control (phenol sol.) and negative control (cell growth medium) Results are expressed as mean ± standard deviation. Statistical significance was determined to * (p ≤ 0.05).