Cell membrane coating for reducing nanoparticle-induced inflammatory responses to scaffold constructs

The controlled release of therapeutics from microparticles or nanoparticles (NPs) has been well-studied. Incorporation of these particles inside biomaterial scaffolds is promising for tissue regeneration and immune modulation. However, these particles may induce inflammatory and foreign body responses to scaffold constructs, limiting their applications. Here we show that widely used poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) formed by double emulsion dramatically increased neutrophil infiltration and pro-inflammatory cytokines in alginate scaffolds 1 day after the subcutaneous injection of the scaffolds into mice. The coating of red blood cell (RBC) membranes on PLGA NPs completely eliminated these short-term inflammatory responses. For a longer term of 10 days, neither PLGA NPs nor RBC membrane-coated NPs exerted a significant effect on the infiltration of neutrophils or macrophages in alginate scaffolds, possibly due to the degradation and/or clearance of NPs by infiltrating cells. Despite the extensive exploration of cell membrane-coated NPs, our study is the first to investigate the effects of cell membrane coating on foreign body reaction to NPs. By harnessing the natural biocompatibility of cell membranes, our strategy of anti-inflammatory protection for scaffolds may be pivotal for many applications such as those relying on the recruitment of stem cells and/or progenitor cells to scaffolds.