Antitumoral-Embedded Biopolymeric Spheres for Implantable Devices

Abstract

The bioactive surface modification of implantable devices paves the way towards the personalized healthcare practice by providing a versatile and tunable approach that increase the patient outcome, facilitate the medical procedure, and reduce the indirect or secondary effects. The purpose of our study was to assess the performance of composite coatings based on biopolymeric spheres of poly(lactide-co-glycolide) embedded with hydroxyapatite (HA) and methotrexate (MTX). Bio-simulated tests performed for up to one week evidenced the gradual release of the antitumor drug and the biomineralization potential of PLGA/HA-MTX sphere coatings. The composite materials proved superior biocompatibility and promoted enhanced cell adhesion and proliferation with respect to human preosteoblast and osteosarcoma cell lines when compared to pristine titanium.

Keywords: PLGA spheres; biodegradable coatings; methotrexate.

Figure 1

Graphic representation of the MTX’s calibration curve at 220 nm (a) and the release profile of MTX from PLGA/HA-MTX sphere coatings under bio-simulated conditions (b).

Figure 2

ATR-FTIR of PLGA/HA-MTX sphere coatings, before and after testing under bio-simulated conditions.

Figure 3

SEM micrographs of initial PLGA/HA-MTX sphere coatings (a,b), SEM image (c) and corresponding EDS spectrum (e), overlapped EDS map (d) and individual EDS maps (f–j) of initial PLGA/HA-MTX sphere coatings.

Figure 4

SEM micrographs of PLGA/HA-MTX sphere coatings after testing under bio-simulated conditions.

Figure 5

EDS maps (a₁–d₁,e,f) and EDS spectra (a₂–d₂) of PLGA/HA-MTX sphere coatings after testing under bio-simulated conditions at 24 h (a₁,a₂), 48 h (b₁,b₂), 72 h (c₁,c₂), 96 h (d₁,d₂), and 168 h (e,f), and graphic representation of the mass variation in PLGA/HA-MTX sphere coatings after testing under bio-simulated conditions (g).

Figure 6

Graphical representation of cell viability and proliferation of (a) human preosteoblasts hFOB 1.19 and (b) human osteosarcoma Saos-2 cells after 24 h and 72 h of contact with PLGA/HA and PLGA/HA-MTX coatings as revealed by the MTT assay (* p value ≤ 0.05, ** p value ≤ 0.01, *** p value ≤ 0.001, **** p value ≤ 0.0001).

Figure 7

Fluorescence micrographs revealing live (green) and dead (red) (a) human preosteoblasts hFOB 1.19 and (b) human osteosarcoma Saos-2 cells after 24 h and 72 h of contact with the non-coated samples, PLGA/HA coatings, and PLGA/HA-MTX coatings (magnification 10×).

Figure 8

Fluorescence micrographs of the cell cytoskeleton of (a) human preosteoblasts hFOB 1.19 and (b) human osteosarcoma Saos-2 cells after 24 h and 72 h of contact with the non-coated samples, PLGA/HA coatings and PLGA/HA-MTX coatings, after staining of the actin filaments with phalloidin-FITC (green) and cell nuclei with DAPI (blue), (magnification 10×).