Defined Surface Physicochemical Cues Inhibit M1 Polarization of Human Macrophages Using Colloidal Self-Assembled Patterns

Biophysical and biochemical cues modulate mammalian cellbehaviorand phenotype simultaneously. Macrophages, indispensable cells inthe innate immune system, respond to external threats such as bacterialinfections and implanted devices, undergoing the classical M1 polarizationto become a pro-inflammatory phenotype. In the study, lipopolysaccharide(LPS)-induced M1 polarization was examined using RAW264.7, THP-1,and primary human PBMCs on a family of artificial extracellular matrix(ECM), named colloidal self-assembled patterns (cSAPs). The resultsshowed that cSAPs were biocompatible, which cannot induce M1 or M2polarization. Interestingly, specific cSAPs (e.g., cSAP3) suppressthe level of M1 polarization (i.e., reduced nitric oxide production,down-regulated gene expression of iNOS, IL-6, TNF-& alpha;, IL-1 & beta;,and TLR4, and reduced proportion of CD11b(+)CD86(+) cells). Transcriptome analysis showed that cell adhesion and cell-ECMinteraction participated in the M1 polarization, and the mechano-sensitivegenes such as PIEZO1 were down-regulated on the cSAP3. More interestingly,these genes were also down-regulated under LPS stimulation, indicatingthat cells became insensitive to the LPS. The abovementioned resultsindicate that the defined physicochemical cues can govern macrophagepolarization. This study illustrates a potential surface design atbiointerface, which is critical in tissue engineering and materiobiology.The outcome is also inspiring in ECM-mediated immune responses.