Switch of macrophage fusion competency by 3D matrices

Abstract

Foreign body reaction reflects the integration between biomaterials and host cells. At the implantation microenvironment, macrophages usually fuse into multinuclear cells, also known as foreign body giant cells, to respond to the biomaterial implants. To understand the biomaterial-induced macrophage fusion, we examined whether biomaterial alone can initiate and control the fusion rate without exogenous cytokines and chemicals. We introduced a collagen-based 3D matrix to embed Raw264.7 cell line and primary rat bone marrow-derived macrophages. We found the biomaterial-stimuli interacted regional macrophages and altered the overall fusogenic protein expressions to regulate the macrophage fusion rate. The fusion rate could be altered by modulating the cell-matrix and cell-cell adhesions. The fused macrophage morphologies, the nuclei number in the fused macrophage, and the fusion rates were matrix dependent. The phenomena were also observed in the in vivo models. These results suggest that the biomaterial-derived stimuli exert similar functions as cytokines to alter the competency of macrophage fusion as well as their drug sensitivity in the biomaterial implanted tissue environment. Furthermore, this in vitro 3D-matrix model has the potential to serve as a toolbox to predict the host tissue response on implanted biomaterials.

The Macrophage-Osteoclast Axis in Osteoimmunity and Osteo-Related Diseases

“…Cell-cell fusion into multinuclei is a sign of osteoclasts differentiation and the specificity of bone tissue. The fusion of macrophages is diverse, including the fusion of macrophages and macrophages, the fusion of macrophages and monocytes, and the fusion of macrophages and other multinucleated cells ( 64 , 65 ). In the bone matrix, mononuclear osteoclasts (macrophages)?…”

Implant Fibrosis and the Underappreciated Role of Myofibroblasts in the Foreign Body Reaction

“…Furthermore, growth on soft culture materials reduces the ability of mouse lineage and human alveolar macrophages to phagocytose micron-sized particles [ 165 ]. Likewise, the fusion of macrophages into FBGCs is enhanced by stiffer, more adhesive and 3D versus 2D implant materials [ 166 ]. In rodent implantation models, macrophage-driven inflammation is reduced around soft versus stiffer materials or when providing the implant with a soft layer, for instance using kPa-soft PEG hydrogels [ 70 ].…”

May the Force Be with You (Or Not): The Immune System under Microgravity

“…The main advantages of 2D tissue plastic cell culture are easier environmental control cell observation, measurement, and eventual manipulation in comparison with 3D cell culture models. As a major consequence non-physiological cell behavior and failure in the translation of cell culture results have been reported [126][127][128][129][130]. To better simulate the in vivo situation, more complex 3D models have been introduced for example using collagen, alginate, or PEG [38,[131][132][133][134].…”