Injectable Oxygen-Carrying Microsphere Hydrogel for Dynamic Regulation of Redox Microenvironment of Wounds.

The delayed healing of infected wounds can be attributed to the increased production of reactive oxygen species (ROS) and consequent damages to vascellum and tissue, resulting in a hypoxic wound environment that further exacerbates inflammation. Current clinical treatments including hyperbaric oxygen therapy and antibiotic treatment fail to provide sustained oxygenation and drug-free resistance to infection. To propose a dynamic oxygen regulation strategy, this study develops a composite hydrogel with ROS-scavenging system and oxygen-releasing microspheres in the wound dressing. The hydrogel itself reduces cellular damage by removing ROS derived from immune cells. Simultaneously, the sustained release of oxygen from microspheres improves cell survival and migration in hypoxic environments, promoting angiogenesis and collagen regeneration. The combination of ROS scavenging and oxygenation enables the wound dressing to achieve drug-free anti-infection through activating immune modulation, inhibiting the secretion of pro-inflammatory cytokines interleukin-6, and promoting tissue regeneration in both acute and infected wounds of rat skins. Thus, the composite hydrogel dressing proposed in this work shows great potential for dynamic redox regulation of infected wounds and accelerates wound healing without drugs.

A Gas Therapy Strategy for Intestinal Flora Regulation and Colitis Treatment by Nanogel-Based Multistage NO Delivery Microcapsules.

Current approaches to treating inflammatory bowel disease focus on the suppression of overactive immune responses, the removal of reactive intestinal oxygen species, and regulation of the intestinal flora. However, owing to the complex structure of the gastrointestinal tract and the influence of mucus, current small-molecule and biologic-based drugs for treating colitis cannot effectively act at the site of colon inflammation, and as a result, they tend to exhibit low efficacies and toxic side effects. In this study, nanogel-based multistage NO delivery microcapsules are developed to achieve NO release at the inflammation site by targeting the inflammatory tissues using the nanogel. Surprisingly, oral administration of the microcapsules suppresses the growth of pathogenic bacteria and increases the abundance of probiotic bacteria. Metabolomics further show that an increased abundance of intestinal probiotics promotes the production of metabolites, including short-chain fatty acids and indole derivatives, which modulate the intestinal immunity and restore the intestinal barrier via the interleukin-17 and PI3K-Akt signaling pathways. This work reveals that the developed gas therapy strategy based on multistage NO delivery microcapsules modulates the intestinal microbial balance, thereby reducing inflammation and promoting intestinal barrier repair, ultimately providing a new therapeutic approach for the clinical management of colitis.

Hierarchical Composite Scaffold with Deferoxamine Delivery System to Promote Bone Regeneration via Optimizing Angiogenesis.

A bone defect refers to the loss of bone tissue caused by trauma or lesion. Bone defects result in high morbidity and deformity rates worldwide. Autologous bone grafting has been widely applied in clinics as the gold standard of treatment; however, it has limitations. Hence, bone tissue engineering has been proposed and developed as a novel therapeutic strategy for treating bone defects. Rapid and effective vascularization is essential for bone regeneration. In this study, a hierarchical composite scaffold with deferoxamine (DFO) delivery system, DFO@GMs-pDA/PCL-HNTs (DGPN), is developed, focusing on vascularized bone regeneration. The hierarchical structure of DGPN imitates the microstructure of natural bone and interacts with the local extracellular matrix, facilitating cell adhesion and proliferation. The addition of 1 wt% of halloysite nanotubes (HNTs) improves the material properties. Hydrophilic and functional groups conferred by polydopamine (pDA) modifications strengthen the scaffold bioactivity. Gelatin microspheres (GMs) protect the pharmacological activity of DFO, achieving local application and sustained release for 7 days. DFO effectively promotes angiogenesis by activating the signaling pathway of hypoxia inducible factor-1 α. In addition, DFO synergizes with HNTs to promote osteogenic differentiation and matrix mineralization. These results indicate that DGPN promotes bone regeneration and accelerates cranial defect healing.

All-Natural Immunomodulatory Bioadhesive Hydrogel Promotes Angiogenesis and Diabetic Wound Healing by Regulating Macrophage Heterogeneity.

Macrophages are highly heterogeneous and exhibit a diversity of functions and phenotypes. They can be divided into pro-inflammatory macrophages (M1) and anti-inflammatory macrophages (M2). Diabetic wounds are characterized by a prolonged inflammatory phase and difficulty in healing due to the accumulation of pro-inflammatory (M1) macrophages in the wound. Therefore, hydrogel dressings with macrophage heterogeneity regulation function hold great promise in promoting diabetic wound healing in clinical applications. However, the precise conversion of pro-inflammatory M1 to anti-inflammatory M2 macrophages by simple and biosafe approaches is still a great challenge. Here, an all-natural hydrogel with the ability to regulate macrophage heterogeneity is developed to promote angiogenesis and diabetic wound healing. The protocatechuic aldehyde hybridized collagen-based all-natural hydrogel exhibits good bioadhesive and antibacterial properties as well as reactive oxygen species scavenging ability. More importantly, the hydrogel is able to convert M1 macrophages into M2 macrophages without the need for any additional ingredients or external intervention. This simple and safe immunomodulatory approach shows great application potential for shortening the inflammatory phase of diabetic wound repair and accelerating wound healing.

Appointment impact and orthodontic emergency occurrence during the coronavirus disease 2019 pandemic: A retrospective study.

INTRODUCTION: This retrospective study aimed to quantify the impact of coronavirus disease 2019 (COVID-19) on the orthodontic appointment and make an analysis of orthodontic emergencies (OEs) that occurred during the pandemic. METHODS: A total of 628 patients were randomly sampled from 3489 subjects who were undergoing active orthodontic treatment with fixed appliances, and the medical records were reviewed. OE occurrence was analyzed from 617 patients who had explicit return-visit records after the COVID-19 outbreak. Wilcoxon signed rank tests, chi-square tests, and a binary logistic regression were performed. RESULTS: The return-visit of 98.6% of the patients was delayed significantly with an increase over 8.98 ± 4.76 weeks (P <0.001). In general, 32.3% of the patients suffered from various OEs while waiting for their first return-visit, and bracket or band debonding was the most frequently reported category. Most OEs did not receive timely treatments because of the lockdown. The incidence was nearly 2 times higher than that of the normal appointment times. No correlation was found between OE occurrence and different demographic and clinical characteristics of patients. The therapeutic progress of patients, especially those in stage 3, was postponed because of the occurrence of OEs. CONCLUSIONS: Regardless of the limitations, our study suggested that it is highly possible that the COVID-19 pandemic has delayed appointments of fixed orthodontic patients. OEs did bother a minority of patients and could not be settled in time during the lockdown, which had a negative impact on the near-term treatment progress and should have been prevented. Further studies are required to investigate the long-dated influence of COVID-19 on orthodontic practices.

Plasma-Derived Exosomes Boost the Healing of Irradiated Wound by Regulating Cell Proliferation and Ferroptosis.

Ionizing radiation (IR) therapy for malignant tumors can damage adjacent tissues, leading to severe wound complications. Plasma-derived exosome treatment has recently emerged as a safe and impactful cell-free therapy. Herein, we aimed to determine whether plasma-derived exosomes could improve the healing of post-radiation wound. Rat plasma-derived exosomes (RP-Exos) were locally injected on cutaneous wounds created on the backs of irradiated rats and boosted the healing process as well as the deposition and remodeling of the extracellular matrix with collagen formation. Subsequently, the effects of RP-Exos were further evaluated on irradiated fibroblasts in vitro. The results suggested that exosomes promoted fibroblast proliferation, migration, cell cycle progression, and cell survival. Moreover, transcriptome sequencing analysis and quantitative polymerase chain reaction validation were performed to identify potential mechanisms. RPExos enhanced the expression of cell proliferation and radioresistance-related genes, and yet downregulated ferroptosis pathway in irradiated fibroblasts. Inhibition of ferroptosis by RP-Exos was further confirmed through colorimetric assay, fluorescence probe and flow cytometry in ferroptosis-induced fibroblasts. Our results suggest that RP-Exos regulate cell proliferation and ferroptosis in irradiated fibroblasts, thereby boosting the healing of irradiated wound. These findings support plasma-derived exosomes as a potential therapeutic method for post-radiation wound complications.