Albumin-impregnated bone granules modulate the interactions between mesenchymal stem cells and monocytes under in vitro inflammatory conditions

Abstract

Bone regeneration around newly implanted biomaterials is a complex process, which in its early phases involves the interactions between Mesenchymal Stem Cells (MSCs) and immune cells. The response of these cells to the biomaterial depends both on the local microenvironment and on the characteristics of the inserted bone substitute. In this work, bone allografts impregnated with albumin are loaded with a co-culture of human MSCs and monocytes; bone granules without albumin are used for comparison. Co-cultures are contextually treated with pro-inflammatory cytokines to simulate the inflammatory milieu naturally present during the bone regeneration process. As revealed by microscopic images, albumin-impregnated bone granules promote adhesion and interactions between cells populations. Compared to control granules, albumin coating diminishes reactive species production by cells. This reduced oxidative stress may be attributable to antioxidant properties of albumin, and it is also reflected in the mitigated gene expression of mitochondrial electron transport chain complexes, where most intracellular reactive molecules are generated. MSCs-monocytes co-cultured onto albumin-impregnated bone granules additionally release higher amounts of immunomodulatory cytokines and growth factors. In summary, this work demonstrates that impregnation of bone granules with albumin positively modulates the interactions between MSCs and immune cells, consequently influencing their mutual activities and immunomodulatory functions.

Keywords: Albumin; Bone substitute; Inflammation; Mesenchymal stem cells; Monocytes.