Abstract
Biocompatibility of layered double hydroxides (LDHs), also known as hydrotalcite-like materials or double metal hydroxides, was investigated by in vivo assays via intramuscular tablets implantation in rat abdominal wall. The tablets were composed by chloride ions intercalated into LDH of magnesium/aluminum (Mg2Al-Cl) and zinc/aluminum (Zn2Al-Cl). The antigenicity and tissue integration capacity of LDHs were assessed histologically after 7 and 28 days post-implantation. No fibrous capsule nearby the LDH was noticed for both materials as well any sign of inflammatory reactions. Sidestream Dark Field imaging, used to monitor in real time the microcirculation in tissues, revealed overall integrity of the microcirculatory network neighboring the tablets, with no blood flow obstruction, bleeding and/or increasing of leukocyte endothelial adhesion. After 28 days Mg2Al-Cl promoted multiple collagen invaginations (mostly collagen type-I) among its fragments while Zn2Al-Cl induced predominantly collagen type–III. This work supports previous results in the literature about LDHs compatibility with living matter, endorsing them as functional materials for biomedical applications.
Highlights
The biocompatibility of Layered Double Hydroxides (LDHs) has been explored by in vitro and in vivo tests as reported in the works already described in this paper, it is observed a lack of studies about intramuscular implantation in order to access the biocompatibility of this class of nanoparticles
LDH samples characterization by chemical analysis, X-ray diffraction (XRD), vibrational spectroscopy and thermal analysis confirm the isolation of layer structured materials with the following compositions: [Mg2.10Al(OH)6.20]Cl∙2.3H2O and [Zn2.08Al(OH)6.16]Cl∙1.7H2O
The first indication of biocompatibility of Mg2Al and Zn2Al samples was the absence of signs of inflammation in the site where the tablets were implanted such as edema, erythema and increase in tissue volume, confirmed by the macroscopic inspection (Fig. 2)
Summary
The biocompatibility of LDH has been explored by in vitro tests such as cell viability tests[12,13], lactate dehydrogenase leakage assay[12,13,14,15], inflammatory mediators analysis[12], hemolysis assay[15,16,17], thrombosis assay[17], lipid peroxidation[18], reactive oxygen species (ROS) generation[12,14] and apoptosis[12,14]. Interesting reports have explored the usage of LDH as a grout material in bone cement for implant in tibia[24], and as a coating to middle ear prostheses[25]. Both studies confirmed that the implants are biocompatible and their performances are enhanced by the LDH presence. As compared to in vitro tests performed in controlled conditions, the in vivo intramuscular implant test allows the activation of full biological host defense by the immune response, being in our opinion a far more adequate test to scrutinize, in short and long periods of observation, the materials biocompatibility and functionality aiming tissue engineering or drug delivery applications. It is emphasized that no drugs or bioactive species were intercalated between LDH layers
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