Cell Membrane-Derived Materials

Biological materials are superior to synthetic biomaterials in biocompatibility and active interactions with cells. Recently, cell membrane-derived nanomaterials (CM-NMs) have been actively explored as a novel class of biological materials with various biomedical applications. However, the fundamental properties of CM-NMs were rarely studied. We first designed new methods to quantitatively study the membrane orientation of red blood cell membrane-coated nanoparticles (RBCM NPs) by conjugating ssDNA probes on cell membranes and cell membrane permeability by a nitrobenzoxadiazole-dithionite ion quenching system. We have demonstrated that membranes maintained a correct outside-out orientation on the majority of NPs, and RBCM NPs have a higher permeability to dithionite ions compared with liposomes and live RBCs. Next, we investigated the effect of cell membrane coating on reducing acute inflammatory responses induced by poly(lactic-co-glycolic acid) NPs to scaffold constructs. The release of therapeutics from the NPs is an important strategy to program cells inside the scaffolds for applications in tissue regeneration and immune modulation. We have demonstrated that coating RBC membranes around NPs can eliminate the NP-induced short-term inflammatory responses to scaffolds, including dramatically increased neutrophil infiltration and pro-inflammatory cytokines. We further developed a new class of biological materials: cell membrane-derived hydrogel scaffolds by using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide-activated alginate to crosslink RBCM vesicles. We have demonstrated that RBCM scaffolds can encapsulate hydrophobic molecules and have the potential to release hydrophobic drugs in a sustained manner. RBCM scaffolds show low neutrophil infiltration after subcutaneous injection in mice, and a significantly higher number of infiltrated macrophages than methacrylate alginate (MA-alginate) scaffolds. According to gene expression and surface markers, these macrophages have an M2-like phenotype, which is anti-inflammatory and immune suppressive. There are also higher percentages of macrophages presenting immunosuppressive PD-L1 in RBCM-scaffolds than in MA-alginate scaffolds. Interestingly, the concentrations of an anti-inflammatory cytokine, IL-10 in both types of scaffolds are higher than those in normal organ tissues. This study paves the way to explore scaffolds derived from other cells that present receptors and/or contain cytokines in regulating immune cells or cells critical for tissue regeneration.