Effect of degradation products of iron-bioresorbable implants on the physiological behavior of macrophages in vitro

Author:

Fagali Natalia S1ORCID,Madrid Marcos A2ORCID,Pérez Maceda Blanca T3,López Fernández María E3,Lozano Puerto Rosa M3ORCID,Fernández Lorenzo de Mele Mónica14ORCID

Affiliation:

1. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), CCT La Plata, CONICET – Facultad de Ciencias Exactas, UNLP, La Plata, Argentina

2. Instituto de Física de Líquidos y Sistemas Biológicos (IFLySiB), CCT La Plata, CONICET – Facultad de Ciencias Exactas, UNLP, La Plata, Argentina

3. Cell-Biomaterial Recognition Lab, Departament of Cellular and Molecular Biology, Centro de Investigaciones Biológicas Margarita Salas (CIB-MS.CSIC), Madrid, Spain

4. Facultad de Ingeniería, UNLP, La Plata, Argentina

Abstract

Abstract The degradation of bioresorbable metals in vivo changes the physicochemical properties in the environment of an implant, such as a stent in the artery wall, and may induce the alteration of the functions of the surrounding cells. The Fe-degradation, from bioresorbable stents, is a particularly intricate process because it leads to the release of soluble (SDP) and insoluble degradation products (IDP) of varied composition. Macrophages are involved in the resorption of the exogenous agents coming from degradation of these materials. In the present work an Fe0 ring, made with a pure Fe wire, in contact with macrophage cell cultures was used to simulate the behaviour of a biodegradable Fe-based implant in a biological environment. Non-invasive time-lapse optical microscopy was applied to obtain images of macrophages exposed to Fe-degradation products, without using staining to avoid distortions and artefacts. It was noticed that as metal degraded, the IDP formed in situ accumulated close to the Fe0 ring. In this zone, the macrophages showed a dynamic process of uptake of dark Fe-containing products, confirmed by SEM-EDX. These macrophages showed alterations in the morphology and decrease in the motility and viability. The inability of the macrophages to move and to degrade the engulfed products caused a long persistence of IDP in the zone closest to the metal. The deleterious effects of IDP accumulated close to the ring, were significantly worse than those observed in the experiments made with (1) concentrated salt solutions (Fe3+ salt 3 mM), with the same amount of precipitates but uniformly distributed in the well, and (2) diluted salt solutions (Fe3+ salt 1 mM) with mainly soluble species. The results were confirmed by standard staining protocols that revealed dead cells close to the Fe0 ring and oxidative stress in cells exposed to both soluble and insoluble species.

Funder

Ministerio de Economía y Competitividad

Consejo Nacional de Investigaciones Científicas y Técnicas

Fondo para la Investigación Científica y Tecnológica

Ministerio de Ciencia, Innovación y Universidades

Universidad Nacional de La Plata

Publisher

Oxford University Press (OUP)

Subject

Metals and Alloys,Biochemistry,Biomaterials,Biophysics,Chemistry (miscellaneous)

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