Research Article: In vitro study of the inflammatory cells response to biodegradable Mg-based alloy extract

Date Published: March 14, 2018

Publisher: Public Library of Science

Author(s): Liang Jin, Jing Wu, Guangyin Yuan, Tongxin Chen, Donghui Zhu.

http://doi.org/10.1371/journal.pone.0193276

Abstract

Biodegradable Mg-based alloys have shown great potential as bone fixation devices or vascular stents. As implant biomaterials, the foreign body reaction (FBR) is an important issue to be studied, where the inflammatory cells play a key role. Here, we used two inflammatory cell lines i.e. THP-1 cells and THP-1 macrophages, to evaluate the effect of Mg–Nd–Zn–Zr alloy (denoted as JDBM) extracts on cell viability, death modes, cell cycle, phagocytosis, differentiation, migration and inflammatory response. The results showed that high-concentration extract induced necrosis and complete damage of cell function. For middle-concentration extract, cell apoptosis and partially impaired cell function were observed. TNF-α expression of macrophages was up-regulated by co-culture with extract in 20% concentration, but was down-regulated in the same concentration in the presence of LPS stimulation. Interestingly, the production of TNF-α decreased when macrophages were cultured in middle and high concentration extracts independent of LPS. Cell viability was also negatively affected by magnesium ions in JDBM extracts, which was a potential factor affecting cell function. Our results provide new information about the impact of Mg alloy extracts on phenotype of immune cells and the potential mechanism, which should be taken into account prior to clinical applications.

Partial Text

Nowadays, metallic biomaterials have been widely used in clinical surgeries, e.g. bone substitute and fixative devices for total hip arthroplasty and bone fracture [1] or vascular stents and drug-eluting scaffolds for ischemic heart disease[2]. Among them, permanent metallic biomaterials, such as stainless steel and titanium alloy, have taken the absolutely major part because of their good performance in mechanical strengths and biocompatibility[3]. However, the drawbacks including second surgery, chronic inflammation and in-stent restenosis have been gradually recognized during their clinical use [4, 5].

Mg-based alloy has been widely used in the clinical management. Nevertheless, FBR is an obstacle for its clinical application. As indicated by previous reports, biomaterials might influence the inflammation response, phagocytosis, migration of macrophages and monocytes [12,24]. Furthermore, Mg-based alloy could degrade according to the following chemical equations: Mg+H2O—Mg(OH)2+H2 and Mg(OH)2+2Cl-—MgCl2+2OH-[25]. Therefore, it should be taken into consideration that massive accumulation of these degradation products due to overburdening the organism regulation or burst release would in turn deteriorate local physical condition [26]. In the present study, we found JDBM extracts in a middle concentration (50%) promoted apoptosis and partly impaired the cell viability of macrophages. For the treatment of JDBM extracts with high concentration (100%), the cells hardly survived even in a short time, while the low concentration (10% and 20%) of JDBM extracts had no effects on cell viability. According to current ISO standard of Part 5, biomaterials is considered as nontoxic if cell viability sustained higher than 75% [27]. We found only the extracts with low concentration could reach the non-toxic standard. However, THP-1 was more adaptive than macrophages to 50% extract as indicated by results of CCK-8 and LDH test. The non-adherent and high proliferative property for THP-1 cells may account for this observation.

JDBM extracts with middle or high concentration might modulate the viability, apoptosis and necrosis of immune cells, while low concentration extract seemed to have no influence. The viability of the immune cells was inhibited by Mg ions produced by degradation of JDBM. JDBM extracts might reduce inflammatory response of macrophages stimulated by LPS through magnesium-based adverse effect on immune cell. Our results provided new evidences on the influence of Mg based alloy on monocyte and macrophages, in terms of phenotype and the potential mechanisms.

 

Source:

http://doi.org/10.1371/journal.pone.0193276

 

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