Large and Externally Positioned Ligand-Coated Nanopatches Facilitate the Adhesion-Dependent Regenerative Polarization of Host Macrophages

Abstract

Macrophages can associate with extracellular matrix (ECM) demonstrating nanosequenced cell-adhesive RGD ligand. In this study, we devised barcoded materials composed of RGD-coated gold and RGD-absent iron nanopatches to show various frequencies and position of RGD-coated nanopatches with similar areas of iron and RGD-gold nanopatches that maintain macroscale and nanoscale RGD density invariant. Iron patches were used for substrate coupling. Both large (low frequency) and externally positioned RGD-coated nanopatches stimulated robust attachment in macrophages, compared with small (high frequency) and internally positioned RGD-coated nanopatches, respectively, which mediate their regenerative/anti-inflammatory M2 polarization. The nanobarcodes exhibited stability in vivo. We shed light into designing ligand-engineered nanostructures in an external position to facilitate host cell attachment, thereby eliciting regenerative host responses.

Geometric Control of Cell Behavior by Biomolecule Nanodistribution

“…Upon verifying that MACRO and MICRO surfaces coated with EphA2 receptors facilitate the attachment of hPSCs, we evaluated whether selected NANO patterns also supported the adhesion and spreading of hPSCs, as these cells have a very narrow area for interactions. There is evidence that many cell types respond specifically to the nanodistribution of biomolecules; however, to date, there has been no reported evidence that hPSCs can specifically attach to such nanopatterned surfaces. − Therefore, we used our optimized concentric hexagonal nanopatterns with (CORE) or without (NO CORE) filled centers combined with a covalently attached L-HT-EphA2 biomolecule. As shown in Figure A, laser scanning confocal microscopy (visualizing the cytoskeleton and nuclei) combined with bright-field microscopy (visualizing the nanostructures) confirmed direct cell interaction with the nanopatterned region.…”

Light-induced dynamic RGD pattern for sequential modulation of macrophage phenotypes

“…ROCK is a crucial regulator of actin cytoskeletal organization and cell-adhesive junctions. The ROCK2 isoform mediates polarization of macrophages, which is considered a molecular switch of macrophage polarization [ 6 , 29 , 53 ]. As shown in Fig.…”

“…Microenvironments of the human body provide dynamic biophysical and biochemical cues that regulate cell fate and organ development [ 1 , 2 ]. To better understand the dynamic interactions between cells and microenvironments to reveal the intrinsic roles of these regulating cues, advanced platforms with dynamic features, such as surface topography [ 3 ], functional ligands [ [4] , [5] , [6] ], and stiffness [ [7] , [8] , [9] ] have attracted much attention [ 10 , 11 ].…”

Multifunctional Magnetic Nanoparticles for Dynamic Imaging and Therapy

“…These results suggest a breakthrough in adoptive transfer immunotherapy for deep‐seated tumors with a well‐developed immunosuppressive microenvironment using remote magnetomechanical activation of immune cells (e.g., macrophages) through magnetic manipulation of the MNPs. [ 131,132 ] To sum up, magnetomechanical signals can stimulate mechanosensitive‐ion channels and receptors, activate immune cells, or physically induce programmed cell death. It can trigger the target molecule from a distance in an intuitive way, but the magnitude of physical force should be elaborated by engineering not only the MNPs but also the electromagnet system and molecular pathway.…”