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

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.

Circulating microRNA-30a-5p, microRNA-101-3p, microRNA-140-3p and microRNA-141-3p as potential biomarkers for dexmedetomidine response in pediatric patients.

PURPOSE: The aim of this study was to investigate the expression levels of plasma miR-30a-5p, miR-101-3p, miR-140-3p and miR-141-3p and their relationship to dexmedetomidine efficacy and adverse effects in pediatric patients. METHODS: The expression levels of miR-30a-5p, miR-101-3p, miR-140-3p and miR-141-3p were measured by qRT-PCR in plasma of 133 pediatric patients receiving dexmedetomidine for preoperative sedation. We analyzed the relationship between miRNA abundance and dexmedetomidine response, including sedative effect and adverse effects, and assessed the predictive power of miRNAs for drug response. RESULTS: Among 133 pediatric patients, 111 patients were dexmedetomidine responders (UMSS ≥ 2) and 22 patients were non-responders (UMSS < 2). We observed higher expression levels of miR-101-3p and miR-140-3p in dexmedetomidine responders compared with non-responders (P < 0.05, P < 0.0001). In contrast, there was no significant difference in the expression levels of miR-30a-5p and miR-141-3p between responders and non-responders (P > 0.05). The plasma levels of miR-101-3p and miR-30a-5p were markedly downregulated in patients who experienced hypotension and bradycardia, respectively (P < 0.05). MiR-101-3p and miR-140-3p demonstrated a potential discriminatory ability between dexmedetomidine responders and non-responders, with AUC of 0.64 (P < 0.05) and 0.77 (P < 0.0001), respectively. The AUC of miR-101-3p in distinguishing patients without hypotension was 0.63 (P < 0.05). The AUC of miR-30a-5p in distinguishing patients without bradycardia was 0.74 (P < 0.05). CONCLUSION: Our study demonstrated that circulating miR-101-3p, miR-140-3p and miR-30a-5p might be used as a blood-based marker for dexmedetomidine efficacy and safety in pediatric patients.

Cobalt ions-derived nanoenzyme array for endosseous neural network reconstruction and osseointegration.

Interactions between bone cells and neurocytes are crucial for endosseous nerve and ensuing bone regeneration. However, absence of neural stem cells in bone makes the innervation of implant osseointegration a major challenge. Herein, a nanorod-like array of sodium hydrogen titanate (ST) co-doped with Co2+ and Co3+, namely STCh that behaves as a reactive oxygen species (ROS)-scavenging enzyme, was hydrothermally formed on Ti substrate. We show that the doped Co2+ and Co3+ locate at TiO6 octahedral interlayers and within octahedra of STCh lattice, appearing releasable and un-releasable, respectively, leading to an increase in Co3+/Co2+ ratio and enzyme activity of the array with immersion. The nanoenzyme-released Co2+ triggers macrophages (MΦs) towards M1 phenotype, then the nanoenzyme scavenges extracellular ROS inducing M1-to-M2 transition. The neurogenic factors secreted by STCh-regulated MΦs, in combination with the released Co2+, promote mesenchymal stem cells to differentiate into neurons and Schwann cells compared to sole Co2+and ST. STCh array greatly enhances nerve reconstruction, type-H capillary formation and ensuing osseointegration in normal rat bone, and antibacteria via engulfing S. aureus by MΦs and osteogenesis in infective case. This nanoenzyme provides an alternative strategy to orchestrate endosseous nerve regeneration for osseointegration without loading exogenous neurotrophins in implants.