Incorporation of Mg particles into PDLLA regulates mesenchymal stem cell and macrophage responses

Abstract

In this work, we investigated a new approach to incorporate Mg particles within a PDLLA matrix using a solvent‐free commercially available process. PDLLA/Mg composites were manufactured by injection moulding and the effects of Mg incorporated into PDLLA on MSC and macrophage responses were evaluated. Small amounts of Mg particles (≤1 wt %) do not cause thermal degradation of PDLLA, which retains its mechanical properties. PDLLA/Mg composites release hydrogen, alkaline products and Mg2+ ions without changing pH of culture media. Mg‐containing materials provide a noncytotoxic environment that enhances MSC viability. Concentration of Mg2+ ions in extracts of MSCs increases with the increment of Mg content in the composites. Incorporation of Mg particles into PDLLA stimulates FN production, ALP activity, and VEGF secretion in MSCs, an effect mediated by degradation products dissolved from the composites. Degradation products of PDLLA induce an increase in MCP‐1, RANTES, and MIP‐1α secretion in macrophages while products of composites have minimal effect on these chemokines. Regulation of MSC behavior at the biomaterial's interface and macrophage‐mediated inflammatory response to the degradation products is related to the incorporation of Mg in the composites. These findings suggest that including small amounts of Mg particles into polymeric devices can be a valuable strategy to promote osseointegration and reduce host inflammatory response. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 866–878, 2016.

Modulating macrophage activities to promote endogenous bone regeneration: Biological mechanisms and engineering approaches

“…In another study, Mg particles were mixed in a PDLLA matrix to enhance MSC viability and osteogenic differentiation. The dissolution of Mg ions from composites was proven to be able to regulate the macrophage-induced inflammatory response evoked by PDLLA degradation components [ 145 , 146 ]. However, micron-size magnesium particles could be engulfed by macrophages, resulting in the necrosis of macrophages and the release of inflammatory cytokines [ 147 ].…”

Comparison of the effects of 45S5 and 1393 bioactive glass microparticles on hMSC behavior

“…Contrary to 45S5 BAG, 1393 BAG is composed of additional K + and Mg 2+ ions. Previous studies have already reported on the positive effects of magnesium ions on cell viability, proliferation, and spreading . Furthermore, it is well documented that hMSCs express cationic channels on their cell membrane and that K + , Na + , and Ca 2+ channels are involved in cell proliferation, migration and differentiation .…”

“…Previous studies have already reported on the positive effects of magnesium ions on cell viability, proliferation, and spreading. 41 Furthermore, it is well documented that hMSCs express cationic channels on their cell membrane and that K 1 , Na 1 , and Ca 21 channels are involved in cell proliferation, migration and differentiation. 42,43 The blocking of Na 1 channels, for instance, increases hMSC proliferation, while blocking calciumactivated K 1 channels results in diminished hMSC proliferation.…”

Characterization and In Vitro and In Vivo Assessment of a Novel Cellulose Acetate-Coated Mg-Based Alloy for Orthopedic Applications

“…In addition, recent studies suggest that Mg ions have the potential to enhance the cell response in the initial phase of the osseointegration process [ 46 , 47 ]. Moreover, Cifuentes et al [ 48 ] have shown that by including small amounts of Mg particles into a poly-D-L-lactic acid (PDLLA) matrix, stimulation of fibronectin production, ALP activity and vascular endothelial growth factor secretion was induced in human bone marrow-derived mesenchymal stem cells as well as a reduction of the inflammatory response exhibited by human THP-1 macrophages.…”