Regulation of Macrophage Polarization Through Periodic Photo‐Thermal Treatment to Facilitate Osteogenesis

Abstract

The richened reactive oxygen species (ROS) and their derived excessive inflammation at bone injured sites hinder osteogenesis of endosseous Ti‐based implants. Herein, anti‐oxidized polydopamine (PDA) is deposited on hydrothermal growth formed hydroxyapatite (HA) nanorods on Ti to form a core‐shell structural nanorod‐like array with HA as a core and PDA as an amorphous shell (PDA@HA), showing not only ROS scavenging ability but also near‐infrared (NIR) light derived photo‐thermal effects. PDA@HA suppresses inflammation based on its ROS scavenging ability to a certain extent, while periodic photo‐thermal treatment (PTT) at a mild temperature (41 ± 1 °C) further accelerates the transition of the macrophages (MΦs) adhered to PDA@HA from the pro‐inflammatory (M1) phenotype to the anti‐inflammatory (M2) phenotype in vitro and in vivo. Transcriptomic analysis reveals that the activation of the PI3K‐Akt1 signaling pathway is responsible for the periodic PTT induced acceleration of the M1‐to‐M2 transition of MΦs. Acting on mesenchymal stem cells (MSCs) with paracrine cytokines of M2 macrophages, PDA@HA with mild PTT greatly promote the osteogenetic functions of MSCs and thus osteogenesis. This work paves a way of employing mildly periodic PTT to induce a favorable immunomodulatory microenvironment for osteogenesis and provides insights into its underlying immunomodulation mechanism.

Bioinspired Piezoelectric Periosteum to Augment Bone Regeneration via Synergistic Immunomodulation and Osteogenesis

“…Furthermore, PDA-functionalized scaffolds have an excellent ROS-scavenging capacity and anti-inflammatory performance, thereby inducing osteogenic differentiation of cells and successful bone regeneration. 60 Collectively, these results confirmed our hypothesis that treatment with the piezoelectric periosteum (PHA/5%PBT and PHA/10%PBT) could enhance the oxidative stress resistance of macrophages by scavenging free radicals and intracellular ROS.…”

“…This agrees with previous studies showing that H 2 O 2 can cross the cell membrane and activate macrophages to produce ROS. 60 In contrast, cells treated with the piezoelectric periosteum exhibited decreased fluorescent signals, and cells treated with PHA/5%PBT and PHA/10% PBT showed negligible green fluorescence, implying a strong protective ability from ROS-induced oxidative damage. An analogous result was found for intracellular ROS clearance by flow cytometry; i.e., the removal of intracellular ROS was enhanced in the PHA/5%PBT and PHA/10%PBT groups (Figure S20).…”

On‐Off Phagocytosis and Switchable Macrophage Activation Stimulated with NIR for Infected Percutaneous Tissue Repair of Polypyrrole‐Coated Sulfonated PEEK

“…The phagocytosis of macrophages can be turned off as NIR is turned on with more subtle temperature control and will be assessed in the future. [64] After bacterial removal, a switch from M1 to M2 macrophage marks the transition from inflammation to tissue regeneration. [65,66] M2 macrophages produce highly expressed anti-inflammatory cytokines, resistance tin-like molecules as repair mediators, and tissue growth factors to promote vascular maturation and maintain vascular and tissue proliferation in the proliferation stage of tissue cells, such as fibroblasts.…”

“…The phagocytosis of macrophages can be turned off as NIR is turned on with more subtle temperature control and will be assessed in the future. [ 64 ]…”

Mussel-inspired adhesive hydrogels for local immunomodulation

“…42 Moreover, ROS scavenging inhibits the RhoA signaling pathway, which is an underlying pathway for PDA-activated M2 macrophage polarization. 83 PDA can also endow materials with immune-evasive properties. Wang et al developed a PDA-inspired conductive ultrasoft hydrogel.…”