CD200 modulates macrophage cytokine secretion and phagocytosis in response to poly(lactic-co-glycolic acid) microparticles and films

Abstract

Biocompatibility is a major concern for developing biomaterials used in medical devices, tissue engineering and drug delivery. Poly(lactic-co-glycolic acid) (PLGA) is one of the most widely used biodegradable materials, yet still triggers a significant foreign body response that impairs healing. Immune cells including macrophages respond to the implanted biomaterial and mediate the host response, which can eventually lead to device failure. Previously in our laboratory, we found that CD200, an immunomodulatory protein, suppressed macrophage inflammatory activation in vitro and reduced local immune cell infiltration around a biomaterial implant. While in our initial study we used polystyrene as a model material, here we investigate the effect of CD200 on PLGA, a commonly used biomaterial with many potential clinical applications. We fabricated PLGA with varied geometries, modified their surfaces with CD200, and examined macrophage cytokine secretion and phagocytosis. We found that CD200 suppressed secretion of the pro-inflammatory cytokine TNF-α and enhanced secretion of the anti-inflammatory cytokine IL-10, suggesting a role for CD200 in promoting wound healing and tissue remodeling. In addition, we found that CD200 increased phagocytosis in both murine macrophages and human monocytes. Together, these data suggest that modification with CD200 leads to a response that simultaneously prevents inflammation and enhances phagocytosis. This immunomodulatory feature may be used as a strategy to mitigate inflammation or deliver drugs or anti-inflammatory agents targeting macrophages.

Incorporation of a Ligand Peptide for Immune Inhibitory Receptor LAIR‐1 on Biomaterial Surfaces Inhibits Macrophage Inflammatory Responses

“…An emerging strategy in biomaterial design leverages direct molecular interactions with immune cells, for example, using biomolecules that bind to and interact with local immune cells, modulating their function. Previously, we reported that modifying biomaterials with CD200, an endogenously expressed self‐associated protein, altered proinflammatory immune responses . We demonstrated that CD200 modification reduced the secretion of proinflammatory cytokines of macrophages, and reduced infiltration of immune cells and reactive oxygen species generation in the tissue surrounding subcutaneously implanted beads.…”

Zwitterionic hydrogels modulate the foreign body response in a modulus-dependent manner

“…Increased cell adhesion did not correlate with an increase in the total protein adsorbed on the hydrogel surface (Figure 4b and Figure 2), but instead was likely dictated by the specific subset of proteins adsorbed that we detected via LC-MS (Figure 3). Recent work has identified specific proteins from serum, like clusterin, that make nanocarriers stealthy in vivo [36] and others have shown that coating materials with specific proteins can inhibit the inflammatory response of macrophages [27,37]. Thus, protein type might be more influential to the FBR than total protein amount.…”

“…Bone marrow-derived macrophages used in the cytokine secretion assay were harvested from the femurs and tibias of 6-10 week-old C57BL/6 mice (Jackson Laboratory) as previously described [27]. Briefly, cells were treated with ACK lysis buffer (Thermo), centrifuged, and resuspended in culture medium containing 10% heat-inactivated FBS and recombinant M-CSF for macrophage differentiation.…”

Biohybrid Nanoparticles to Negotiate with Biological Barriers

“…For instance, polystyrene NPs with surface carboxyl‐(PS‐COOH) and amino‐(PS‐NH 2 ) groups could strongly skew the M2 macrophage polarization without affecting M1 markers . Incorporation of signaling proteins such as CD200 with NPs could also influence the macrophages polarization …”