Immunoregulation of macrophages by dynamic ligand presentation via ligand–cation coordination

Abstract

Macrophages regulate host responses to implants through their dynamic adhesion, release, and activation. Herein, we employ bisphosphonate (BP)-coated gold nanoparticle template (BNP) to direct the swift and convertible formation of Mg 2+ -functional Mg 2+ -BP nanoparticle (NP) on the BP-AuNP surface via reversible Mg 2+ -BP coordination, thus producing (Mg 2+ -BP)-Au dimer (MgBNP). Ethylenediaminetetraacetic acid-based Mg 2+ chelation facilitates the dissolution of Mg 2+ -BP NP, thus enabling the reversion of the MgBNP to the BNP. This convertible nanoassembly incorporating cell-adhesive Mg 2+ moieties directs reversible attachment and detachment of macrophages by BP and EDTA, without physical scraping or trypsin that could damage cells. The swift formation of RGD ligand- and Mg 2+ -bifunctional RGD-Mg 2+ -BP NP that yields (RGD-Mg 2+ -BP)-Au dimer (RGDBNP) further stimulates the adhesion and pro-regenerative M2-type polarization of macrophages, both in vitro and in vivo, including rho-associated protein kinase. This swift and non-toxic dimer formation can include diverse bio-functional moieties to regulate host responses to implants.

<p>The Role of Autophagy in M2 Polarization of Macrophages Induced by Micro/Nano Topography</p>

“…According to previous reports, manipulating cell adhesive ligands to formulate proper nanotopography is able to control macrophage polarization directions. 40,41 Therefore, our implant surface may have influenced the cell adhesion organization, thus resulting in ERK pathway activation.…”

Investigations on the Mechanical Properties of Glass Fiber/Sisal Fiber/Chitosan Reinforced Hybrid Polymer Sandwich Composite Scaffolds for Bone Fracture Fixation Applications

“…They found that immobilized Wnt5a mimetic ligand-activated noncanonical Wnt signaling leading to enhanced intracellular calcium level, F-actin stability, actomyosin contractility, and cell adhesion structure development [40]. Kang et al (2019) suggested that macrophages play a significant role in regulating foreign body response in biomaterials. The macrophages in biomaterials can reversibly convert their cell adhesion and promote the tissue healing processes by regulating the inflammatory of tissues [41].…”

Nanotextured silk fibroin/hydroxyapatite biomimetic bilayer tough structure regulated osteogenic/chondrogenic differentiation of mesenchymal stem cells for osteochondral repair

“…The bio‐functionalization of developed biomaterials was conducive to further enhance its bioactivity. It is well known that surface nanostructures or decoration of bioactive motifs could regulate cells behaviours, and greatly improve the potential of cell differentiation, which is the key factor to the success of the implanted scaffolds 17,44,45 . For example, a noncanonical Wnt5a motif could functionalize biomaterials in enhancing the osteogenesis and associated skeleton formation 44 .…”