In vitro modulation of the behavior of adhering macrophages by medications is biomaterial-dependent

Abstract

After implantation of a biomaterial, an inflammatory response involving macrophages is induced. The behavior of macrophages depends on their phenotype, and by directing macrophage polarization unwanted effects may be avoided. In this study, the possibility to modulate the behavior of macrophages activated by biomaterials was assessed in an in vitro model. Primary human monocytes were seeded on polyethylene terephthalate, polypropylene and polylactic acid yarns, and treated with medications frequently used by patients: rapamycin, dexamethasone, celecoxib or pravastatin. Modulation of the adhering macrophages with rapamycin resulted in a generally pro-inflammatory effect. Dexamethasone caused an overall anti-inflammatory effect on the macrophages cultured on either material, while celecoxib only affected macrophages adhering to polyethylene terephthalate and polylactic acid. Pravastatin increased the pro-inflammatory genes of macrophages cultured on polypropylene and polylactic acid. Pairwise comparison revealed that macrophages adhering to polylactic acid seemed to be more susceptible to phenotype modulation than when adhering to polypropylene or polyethylene terephthalate. The data show that macrophages activated by the biomaterials can be modulated, yet the degree of the modulatory capacity depends on the type of material. Combined, this model provides insights into the possibility of using a medication in combination with a biomaterial to direct macrophage behavior and thereby possibly avoid unwanted effects after implantation.

Assessing the response of human primary macrophages to defined fibrous architectures fabricated by melt electrowriting

“…For PCL scaffolds, to avoid the interference of cells deposited through the pores on the bottom surface of the wells, PCL scaffolds were transferred to clean wells 3 h after cell seeding. Cells were cultivated for 3 days on scaffolds or films, in line with previous studies testing macrophage response to biomaterials [ 22 , 35 , 36 ]. In this last phase, culture medium (RPMI-1640 with 10% heat-inactivated FBS and 1% PSG) did not contain M-CSF or polarizing cytokines.…”

Transcriptome-targeted analysis of human peripheral blood-derived macrophages when cultured on biomaterial meshes

“…Alloderm® is sourced from cadaveric human skin and was chosen as a representative absorbable acellular matrix [52]. Previous studies have reported, to some extent, the Mϕ response towards these biomaterials, but the in vitro response of human Mϕs towards P4HB based biomaterials remains mostly under-explored [34,[53][54][55][56][57][58][59].…”

Effect of molecular weight of tyramine-modified hyaluronan on polarization state of THP-1 and peripheral blood mononuclear cells-derived macrophages

“…No donor information was received as per local regulations. Obtained peripheral blood mononuclear cells (PMBCs) were labelled with CD14 magnetic beads followed by magnetic-activated cell sorting (MACS) [51, 52]. CD14 + monocytes cells were resuspended in RPMI medium supplemented with 10% FBS and then seeded onto tissue culture plastic at a density of 1.82 x 10 5 cells well -1 for D1, and at a density of 3.0 x 10 5 cells well -1 for donors D2 and D3, both in the presence of 20 ng mL -1 human macrophage colony-stimulating factor (hM-CSF) for 5 days.…”