Implications of MCU complex in metabolic diseases.

Metabolic diseases are considered the primary culprit for physical and mental health of individuals. Although the diagnosis of these diseases is relatively easy, more effective and convenient potent drugs are still being explored. Ca2+ across the inner mitochondrial membrane is a vital intracellular messenger that regulates energy metabolism and cellular Ca2+ homeostasis and is involved in cell death. Mitochondria rely on a selective mitochondrial Ca2+ unidirectional transport complex (MCU complex) in their inner membrane for Ca2+ uptake. We found that the channel contains several subunits and undergoes dramatic transformations in various pathological processes, especially in metabolic diseases. In this way, we believe that the MCU complex becomes a target with significant potential for these diseases. However, there is no review linking the two factors, thus hindering the possibility of new drug production. Here, we highlight the connection between MCU complex-related Ca2+ transport and the pathophysiology of metabolic diseases, adding understanding and insight at the molecular level to provide new insights for targeting MCU to reverse metabolism-related diseases.

The role of mitochondria in the peri-implant microenvironment.

NEW FINDINGS: What is the topic of this review? In this review, we consider the key role of mitochondria in the peri-implant milieu, including the regulation of mitochondrial reactive oxygen species and mitochondrial metabolism in angiogenesis, the polarization of macrophage immune responses, and bone formation and bone resorption during osseointegration. What advances does it highlight? Mitochondria contribute to the behaviours of peri-implant cell lines based on metabolic and reactive oxygen species signalling modulations, which will contribute to the research field and the development of new treatment strategies for improving implant success. ABSTRACT: Osseointegration is a dynamic biological process in the local microenvironment adjacent to a bone implant, which is crucial for implant performance and success of the implant surgery. Recently, the role of mitochondria in the peri-implant microenvironment during osseointegration has gained much attention. Mitochondrial regulation has been verified to be essential for cellular events in osseointegration and as a therapeutic target for peri-implant diseases in the peri-implant microenvironment. In this review, we summarize our current knowledge of the key role of mitochondria in the peri-implant milieu, including the regulation of mitochondrial reactive oxygen species and mitochondrial metabolism in angiogenesis, the polarization of macrophage immune responses, and bone formation and resorption during osseointegration, which will contribute to the research field and the development of new treatment strategies to improve implant success. In addition, we indicate limitations in our current understanding of the regulation of mitochondria in osseointegration and suggest topics for further study.

Hydrogel armed with Bmp2 mRNA-enriched exosomes enhances bone regeneration.

BACKGROUND: Sustained release of bioactive BMP2 (bone morphogenetic protein-2) is important for bone regeneration, while the intrinsic short half-life of BMP2 at protein level cannot meet the clinical need. In this study, we aimed to design Bmp2 mRNA-enriched engineered exosomes, which were then loaded into specific hydrogel to achieve sustained release for more efficient and safe bone regeneration. RESULTS: Bmp2 mRNA was enriched into exosomes by selective inhibition of translation in donor cells, in which NoBody (non-annotated P-body dissociating polypeptide, a protein that inhibits mRNA translation) and modified engineered BMP2 plasmids were co-transfected. The derived exosomes were named ExoBMP2+NoBody. In vitro experiments confirmed that ExoBMP2+NoBody had higher abundance of Bmp2 mRNA and thus stronger osteogenic induction capacity. When loaded into GelMA hydrogel via ally-L-glycine modified CP05 linker, the exosomes could be slowly released and thus ensure prolonged effect of BMP2 when endocytosed by the recipient cells. In the in vivo calvarial defect model, ExoBMP2+NoBody-loaded GelMA displayed great capacity in promoting bone regeneration. CONCLUSIONS: Together, the proposed ExoBMP2+NoBody-loaded GelMA can provide an efficient and innovative strategy for bone regeneration.

Emerging roles of HMGB1-related lncRNA: from molecular biology to clinical application.

High-mobility group box 1 (HMGB1) not only induces cell proliferation and migration but also promotes cell apoptosis and autophagy. Abnormal expression of HMGB1 in plasma or body fluids could be detected in the occurrence and development of inflammation, cardiovascular disease, immune diseases, and cancer. In recent years, the accumulating research on lncRNAs had led us to the important role of lncRNAs in finely regulating the expression of molecules. Nevertheless, the roles of lncRNAs in upregulating HMGB1 and its receptors remain elusive. This article systematically summarizes the lncRNAs related to HMGB1 and its essential receptors such as RAGE. Multiple lncRNAs, such as lncRNA MALAT1 were proposed to regulate HMGB1 and its receptors upstream. As HMGB1-related diseases were summarized, we also expected predictable application prospects of both HMGB1 and related lncRNAs. The in-depth research focusing on lncRNAs behind HMGB1 and its receptors might provide a novel foundation for therapeutic treatment of HMGB1-related disorders, together with targets regarding HMGB1.

ROS triggered local delivery of stealth exosomes to tumors for enhanced chemo/photodynamic therapy.

BACKGROUND: Exosomes are recognized as effective platforms for targeted delivery for their high physicochemical stability and biocompatibility. However, most of the exosomes are inevitably and rapidly cleared by mononuclear phagocytic system (MPS) during cancer therapy. How to engineer exosome to enhance the delivery efficiency is being intensively explored. In this study, we have constructed mPEG2000-TK-CP05 decorated exosomes as effective delivery platforms to achieve enhanced photodynamic/chemical cancer therapy. RESULTS: Exosomes were coated with CP05-TK-mPEG2000, in which CP05 is a peptide with high affinity to exosomal CD63 and TK could be cleaved by ROS. The resulted exosomes, namely stealth Exo, were electroporated to load RB (photosensitizer Rose Bengal) and Dox (Doxorubicin). We verified that the Stealth Exo@RB (Stealth Exo additionally loaded with RB) could escape MPS while accumulate in the tumor region efficiently in the xenograft model when laser irradiation conducted locally. Additionally, we revealed that the Stealth Exo serves as an efficient platform for Dox delivery. Dox, together with the RB mediated photodynamic therapy induce tumor cell damage synergistically in the tumor region. Moreover, the proposed switchable stealth exosomes minimized the dose of toxic Dox and thus allowed robust tumor immune response. CONCLUSIONS: Our results indicated that the proposed Stealth Exo greatly improves both the accessibility and efficiency of drug delivery, with minimal chemical or genetic engineering. The proposed Stealth Exo serve as a promising and powerful drug delivery nanoplatform in cancer treatment.

Growth Factor-Decorated Ti3 C2 MXene/MoS2 2D Bio-Heterojunctions with Quad-Channel Photonic Disinfection for Effective Regeneration of Bacteria-Invaded Cutaneous Tissue.

Phototherapy has recently emerged as a competent alternative for combating bacterial infection without antibiotic-resistance risk. However, owing to the bacterial endogenous antioxidative glutathione (GSH), the exogenous reactive oxygen species (ROS) generated by phototherapy can hardly behave desired antibacterial effect. To address the daunting issue, a quad-channel synergistic antibacterial nano-platform of Ti3 C2 MXene/MoS2 (MM) 2D bio-heterojunctions (2D bio-HJs) are devised and fabricated, which possess photothermal, photodynamic, peroxidase-like (POD-like), and glutathione oxidase-like properties. Under near-infrared (NIR) laser exposure, the 2D bio-HJs both yield localized heating and raise extracellular ROS level, leading to bacterial inactivation. Synchronously, Mo4+ ions can easily invade into ruptured bacterial membrane, arouse intracellular ROS, and deplete intracellular GSH. Squeezed between the "ROS hurricane" from both internal and external sides, the bacteria are hugely slaughtered. After being further loaded with fibroblast growth factor-21 (FGF21), the 2D bio-HJs exhibit benign cytocompatibility and boost cell migration in vitro. Notably, the in vivo evaluations employing a mouse-infected wound model demonstrate the excellent photonic disinfection towards bacterial infection and accelerated wound healing. Overall, this work provides a powerful nano-platform for the effective regeneration of bacteria-invaded cutaneous tissue using 2D bio-HJs.

Leptin attenuates hypoxia-induced apoptosis in human periodontal ligament cells via the reactive oxygen species-hypoxia-inducible factor-1α pathway.

NEW FINDINGS: What is the central question of this study? Does leptin have an effect on hypoxia-induced apoptosis in human periodontal ligament cells (hPDLCs), and what is the potential underlying mechanism? What is the main finding and its importance? Hypoxia induces cell apoptosis and leptin expression in hPDLCs through the induction of hypoxia-inducible factor-1α and accumulation of reactive oxygen species (ROS). Leptin shows feedback inhibition on hypoxia-induced ROS-mediated apoptosis in hPDLCs, suggesting a new application of leptin for hypoxic damage in periodontal diseases. ABSTRACT: Hypoxia-induced apoptosis of human periodontal ligament cells (hPDLCs) is an important contributor to the progression of various periodontal diseases. Although leptin has been shown to protect connective tissue cells against hypoxia-induced injury, whether it might do so by attenuating hypoxia-induced apoptosis in hPDLCs remains unclear. Here, using CoCl2 treatment, we simulated hypoxic conditions in hPDLCs and explored whether apoptosis and reactive oxygen species (ROS) levels were related to hypoxia. After small interfering RNA (siRNA) inhibition of leptin and hypoxia-inducible factor-1α (HIF-1α), the levels of apoptosis, ROS and leptin expression were measured. We showed that in CoCl2 -treated hPDLCs, significantly higher cell apoptosis rates and ROS accumulation were observed. Cobalt chloride also increased leptin and HIF-1α expression in hPDLCs. Further investigation of the pathway demonstrated that inhibition of ROS attenuated hypoxia-induced cell apoptosis and leptin expression, whereas siRNA inhibition of leptin aggravated hypoxia-induced cell apoptosis and ROS accumulation. Hypoxia induces cell apoptosis and leptin expression in hPDLCs through the induction of ROS and HIF-1α pathways, and leptin shows feedback inhibition on ROS-mediated apoptosis in hPDLCs. These findings suggest a new application of leptin for hypoxic damage in periodontal diseases.

Sirtuin 3 deficiency exacerbates age-related periodontal disease.

BACKGROUND: Sirtuin 3 (SIRT3), a mitochondrial NAD+ -dependent deacetylase, has received much attention for its effect on metabolism and aging. However, the role of SIRT3 in periodontal disease remains unknown. OBJECTIVE: This study aimed to investigate the functional role of SIRT3 in age-related periodontal disease and underlying mechanisms. METHODS: Sixteen mice were randomly assigned into four groups: the young wild type (WT), the aged WT, the young SIRT3-knockout (KO), and the aged SIRT3-KO. SIRT3 and cyclophilin D (CypD) expression and protein lysine acetylation levels in alveolar bones were detected by western blot. The bone architecture and the distance of CEJ-ABC were assessed using micro-CT and HE staining. The osteoclast number was observed through tartrate-resistant acid phosphatase (TRAP) staining. Mitochondrial morphology in SIRT3 knockdown MC3T3-E1 osteoblastic cells was analyzed by Immunofluorescence staining. In gingival tissues, the NAD+ /NADH ratio was measured, and oxidative stress was detected by MitoSOX staining, HO-1 staining, and MnSOD expression. Mitochondrial biogenesis was measured by PGC-1α expression and oxygen consumption rate (OCR). RESULTS: In parallel with the imbalanced NAD+ /NADH ratio, the SIRT3 expression was significantly decreased in the alveolar bones of the aged mice, accompanied by a global elevation of protein acetylation levels. The aged SIRT3-KO group showed the highest rate of bone resorption and the largest number of TRAP-positive osteoclasts among the four groups. Moreover, the reactive oxygen species level was up-regulated in the young and the aged SIRT3-KO groups. SIRT3 deficiency promoted mitochondrial fission and increased the CypD expression. Furthermore, the lack of SIRT3 reduced the PGC-1α expression in gingival tissues and exhibited a significant reduction in maximal OCR. CONCLUSION: Reduced SIRT3 abundance contributes to aged-related periodontal disease via the exacerbation of oxidative stress and mitochondrial dysfunction.

Uprighting a mesially tilted mandibular left second molar with anchorage from a dental implant.

Mesial tilting of adjacent teeth may appear after the removal of a tooth, leading to a lack of restorative space. This dental technique presents a method of uprighting a mesially tilted adjacent tooth by using a dental implant as anchorage.

CoCl2 induces apoptosis via a ROS-dependent pathway and Drp1-mediated mitochondria fission in periodontal ligament stem cells.

Oxygen deficiency is associated with various oral diseases, including chronic periodontitis, age-related alveolar bone loss, and mechanical stress-linked cell injury from orthodontic appliances. Nevertheless, our understanding of the impact of hypoxia on periodontal tissues and its biochemical mechanism is still rudimentary. The purpose of this research was to elucidate the effects of hypoxia on the apoptosis of human periodontal ligament stem cells (PDLSCs) in vitro and the underlying mechanism. Herein, we showed that cobalt chloride (CoCl2) triggered cell dysfunction in human PDLSCs in a concentration-dependent manner and resulted in cell apoptosis and oxidative stress overproduction and accumulation in PDLSCs. In addition, CoCl2 promoted mitochondrial fission in PDLSCs. Importantly, CoCl2 increased the expression of dynamin-related protein 1 (Drp1), the major regulator in mitochondrial fission, in PDLSCs. Mitochondrial division inhibitor-1, pharmacological inhibition of Drp1, not only inhibited mitochondrial fission but also protected against CoCl2-induced PDLSC dysfunction, as shown by increased mitochondrial membrane potential, increased ATP level, reduced reactive oxygen species (ROS) level, and decreased apoptosis. Furthermore, N-acety-l-cysteine, a pharmacological inhibitor of ROS, also abolished CoCl2-induced expression of Drp1 and protected against CoCl2-induced PDLSC dysfunction, as shown by restored mitochondrial membrane potential, ATP level, inhibited mitochondrial fission, and decreased apoptosis. Collectively, our data provide new insights into the role of the ROS-Drp1-dependent mitochondrial pathway in CoCl2-induced apoptosis in PDLSCs, indicating that ROS and Drp1 are promising therapeutic targets for the treatment of CoCl2-induced PDLSC dysfunction.

The cyclophilin D/Drp1 axis regulates mitochondrial fission contributing to oxidative stress-induced mitochondrial dysfunctions in SH-SY5Y cells.

Oxidative stress plays a central role in the pathogenesis of various neurodegenerative diseases. Increasing evidences have demonstrated that structural abnormalities in mitochondria are involved in oxidative stress related nerve cell damage. And Drp1 plays a critical role in mitochondrial dynamic imbalance insulted by oxidative stress-derived mitochondria. However, the status of mitochondrial fusion and fission pathway and its relationship with mitochondrial properties such as mitochondrial membrane permeability transition pore (mPTP) have not been fully elucidated. Here, we demonstrated for the first time the role of Cyclophilin D (CypD), a crucial component for mPTP formation, in the regulation of mitochondrial dynamics in oxidative stress treated nerve cell. We observed that CypD-mediated phosphorylation of Drp1 and subsequently augmented Drp1 recruitment to mitochondria and shifts mitochondrial dynamics toward excessive fission, which contributes to the mitochondrial structural and functional dysfunctions in oxidative stress-treated nerve cells. CypD depletion or over expression accompanies mitochondrial dynamics/functions recovery or aggravation separately. We also demonstrated first time the link between the CypD to mitochondrial dynamics. Our data offer new insights into the mechanism of mitochondrial dynamics which contribute to the mitochondrial dysfunctions, specifically the role of CypD in Drp1-mediated mitochondrial fission. The protective effect of CsA, or other molecules affecting the function of CypD hold promise as a potential novel therapeutic strategy for governing oxidative stress pathology via mitochondrial pathways.

Association of circulating leptin and adiponectin with periodontitis: a systematic review and meta-analysis.

BACKGROUND: This study aimed to assess the difference in serum levels of leptin and adiponectin in patients with periodontitis and in periodontally healthy individuals and evaluate the changes in circulating leptin and adiponectin after periodontal therapy. Leptin and adiponectin are the most generally studied adipokines that function as inflammatory cytokines. Although the association between periodontitis and serum levels of leptin and adiponectin has been studied extensively, the results were not consistent. METHODS: A systematic search of the Pubmed, Embase, Web of Science, and Cochrane Library up to September 2016 was conducted. The studies were screened and selected by two writers according to the specific eligibility criteria. The quality of included cross-sectional studies was assessed using the quality assessment form recommended by the Agency for Healthcare Research and Quality and Methodological Index for Nonrandomized Studies. The meta-analyses were conducted using the STATA 12.0 software. RESULTS: A total of 399 manuscripts were yielded and 25 studies were included in the present meta-analysis. Significantly elevated serum levels of leptin and decreased serum levels of adiponectin in patients with periodontitis were observed in the subgroup analysis of body mass index (BMI) <30. The overall and subgroup analyses showed no significant change in the serum levels of leptin in patients with periodontitis after periodontal treatment. The subgroup analysis of systemically healthy patients showed no significant change in serum levels of adiponectin in patients with periodontitis after periodontal treatment. CONCLUSIONS: The present meta-analysis supported elevated serum levels of leptin and decreased serum levels of adiponectin in patients with periodontitis compared with controls in the BMI <30 population. In systemically healthy patients with periodontitis, serum levels of leptin and adiponectin do not significantly change after periodontal treatment.

Reactive oxygen species regulatory mechanisms associated with rapid response of MC3T3-E1 cells for vibration stress.

Although many previous studies have shown that refractory period-dependent memory effect of vibration stress is anabolic for skeletal homeostasis, little is known about the rapid response of osteoblasts simply derived from vibration itself. In view of the potential role of reactive oxygen species (ROS) in mediating differentiated activity of osteoblasts, whether and how ROS regulates the rapid effect of vibration deserve to be demonstrated. Our findings indicated that MC3T3-E1 cells underwent decreased gene expression of Runx2, Col-I and ALP and impaired ALP activity accompanied by increased mitochondrial fission immediately after vibration loading. Moreover, we also revealed the involvement of ERK-Drp1 signal transduction in ROS regulatory mechanisms responsible for the rapid effect of vibration stress.

Inhibition of ERK-DLP1 signaling and mitochondrial division alleviates mitochondrial dysfunction in Alzheimer's disease cybrid cell.

Mitochondrial dysfunction is an early pathological feature of Alzheimer's disease (AD). The underlying mechanisms and strategies to repair it remain unclear. Here, we demonstrate for the first time the direct consequences and potential mechanisms of mitochondrial functional defects associated with abnormal mitochondrial dynamics in AD. Using cytoplasmic hybrid (cybrid) neurons with incorporated platelet mitochondria from AD and age-matched non-AD human subjects into mitochondrial DNA (mtDNA)-depleted neuronal cells, we observed that AD cybrid cells had significant changes in morphology and function; such changes associate with altered expression and distribution of dynamin-like protein (DLP1) and mitofusin 2 (Mfn2). Treatment with antioxidant protects against AD mitochondria-induced extracellular signal-regulated kinase (ERK) activation and mitochondrial fission-fusion imbalances. Notably, inhibition of ERK activation not only attenuates aberrant mitochondrial morphology and function but also restores the mitochondrial fission and fusion balance. These effects suggest a role of oxidative stress-mediated ERK signal transduction in modulation of mitochondrial fission and fusion events. Further, blockade of the mitochondrial fission protein DLP1 by a genetic manipulation with a dominant negative DLP1 (DLP1(K38A)), its expression with siRNA-DLP1, or inhibition of mitochondrial division with mdivi-1 attenuates mitochondrial functional defects observed in AD cybrid cells. Our results provide new insights into mitochondrial dysfunction resulting from changes in the ERK-fission/fusion (DLP1) machinery and signaling pathway. The protective effect of mdivi-1 and inhibition of ERK signaling on maintenance of normal mitochondrial structure and function holds promise as a potential novel therapeutic strategy for AD.

Mechanical stretch endows mesenchymal stem cells stronger angiogenic and anti-apoptotic capacities via NFκB activation.

Mesenchymal stem cells (MSCs) have been broadly used for tissue regeneration and repair due to their broad differentiation potential and potent paracrine properties such as angiogenic capacity. Strategies to increase their survival rate after transplantation and the angiogenic ability are of priority for the utility of MSCs. In this study, we found that mechanical stretch (10% extension, 30 cycles/min cyclic stretch) preconditioning increase the angiogenic capacity via VEGFA induction. In addition, mechanical stretch also increases the survival rate of mesenchymal stem cells under nutrients deprivation. Consistent with the increase VEGFA expression and resistance to apoptosis, nuclear localization of NFκB activity p65 increased upon mechanical stretch. Inhibition of NFκB activity by BAY 11-708 blocks the pro-angiogenesis and anti-apoptosis function of mechanical stretch. Taken together, our findings here raise the possibility that mechanical stretch preconditioning might enhance the therapeutic efficacy of mesenchymal stem cells.

Blockade of Drp1 rescues oxidative stress-induced osteoblast dysfunction.

Osteoblast dysfunction, induced by oxidative stress, plays a critical role in the pathophysiology of osteoporosis. However, the underlying mechanisms remain unclarified. Imbalance of mitochondrial dynamics has been closely linked to oxidative stress. Here, we reveal an unexplored role of dynamic related protein 1(Drp1), the major regulator in mitochondrial fission, in the oxidative stress-induced osteoblast injury model. We demonstrate that levels of phosphorylation and expression of Drp1 significantly increased under oxidative stress. Blockade of Drp1, through pharmaceutical inhibitor or gene knockdown, significantly protected against H2O2-induced osteoblast dysfunction, as shown by increased cell viability, improved cellular alkaline phosphatase (ALP) activity and mineralization and restored mitochondrial function. The protective effects of blocking Drp1 in H2O2-induced osteoblast dysfunction were evidenced by increased mitochondrial function and suppressed production of reactive oxygen species (ROS). These findings provide new insights into the role of the Drp1-dependent mitochondrial pathway in the pathology of osteoporosis, indicating that the Drp1 pathway may be targetable for the development of new therapeutic approaches in the prevention and the treatment of osteoporosis.

GelMA/κ-carrageenan double-network hydrogels with superior mechanics and biocompatibility.

Hydrogels are crosslinked hydrophilic polymer networks of high-water content. Although they have been widely investigated, preparing hydrogels with excellent mechanical properties and biocompatibility remains a challenge. In the present work, we developed a novel GelMA/κ-carrageenan (GelMA/KC) double network (DN) hydrogel through a dual crosslinking strategy. The three-dimensional (3D) microstructure of KC is the first network, and covalently crosslinked on the κ-carrageenan backbone is the second network. The GelMA/KC hydrogel shows advantages in physical properties, including higher compression strength (10% GelMA/1% KC group, 130 kPa) and Young's modulus (10% GelMA/1% KC group, 300), suggesting its excellent elasticity and compressive capability. When using a higher concentration of GelMA, the hybrid hydrogel has even higher mechanical properties. In addition, the GelMA/KC hydrogel is favorable for cell spreading and proliferation, demonstrating its excellent biocompatibility. This study provides a new possibility for a biodegradable and high-strength hydrogel as a new generation material of orthopedic implants.

Perturbation of mitochondrial dynamics links to the aggravation of periodontitis by diabetes.

Diabetes and periodontitis are prevalent diseases that considerably impact global economy and diabetes is a major risk factor of periodontitis. Mitochondrial dynamic alterations are involved in many diseases including diabetes and this study aims to evaluate their relevance with diabetes aggravated periodontitis. Sixty mice are randomly divided into 4 groups: control, periodontitis, diabetes and diabetic periodontitis. Periodontitis severity is evaluated by alveolar bone loss, inflammation and oxidative stress status. Mitochondrial structural and functional defects are evaluated by the mitochondrial fission/fusion events, mitochondrial reactive oxygen species (ROS) accumulation, complex activities and adenosine triphosphate (ATP) production. Advanced glycation end product (AGE) and Porphyromonas gingivalis are closely related to periodontitis occurrence and development. Human gingival fibroblast cells (HGF-1) are used to investigate the AGE role and lipopolysaccharide (LPS) from Porphyromonas gingivalis (P-LPS) in aggravating diabetic periodontitis by mitochondrial dynamic and function alterations. In vivo, diabetic mice with periodontitis show severe bone loss, increased inflammation and oxidative stress accumulation. Among mice with periodontitis, diabetic mice show worse mitochondrial dynamic perturbations than lean mice, along with fusion protein levels inducing more mitochondrial fission in gingival tissue. In vitro, AGEs and P-LPS co-treatment causes severe.

Photonic double-network hydrogel dressings for antibacterial phototherapy and inflammation regulation in the general management of cutaneous regeneration.

The treatment of festering pathogenic bacteria-induced skin wounds with increased inflammation is an ongoing challenge. The traditional antibacterial photothermal therapy always results in localized hyperthermia (over 50 °C), which inevitably delays tissue recovery. To address this serious issue, we devise a novel photonic hydrogel by integrating urchin-like Bi2S3 nano-heterojunctions (nano-HJs) into double-network hydrogels for infected skin regeneration. The synergy of NIR-triggered heat and ROS enables the hydrogels to achieve a rapid germicidal efficacy against bacteria within 15 min at mild temperature (below 50 °C). In vitro cell analysis results revealed that the photonic hydrogels exhibit superior cytocompatibility even after NIR illumination. More importantly, an in vivo study demonstrated that the photonic hydrogel dressings have a robust ability of accelerating contagious full-thickness wound regeneration through debriding abscesses, eliminating pathogens, improving collagen deposition, promoting angiogenesis, and adjusting the inflammation state. This photonic hydrogel system provides a general management strategy for the remedy of infectious wounds, where the incorporation of nano-HJs endows the hydrogels with the photodisinfection ability; in addition, the multifunctional hydrogels alleviate the damage from overwhelming heat towards surrounding tissues during phototherapy and steer the inflammation during the process of tissue regeneration. Accordingly, this work highlights the promising application of the photonic hydrogels in conquering refractory pathogen-invaded infection.

Glucose-primed PEEK orthopedic implants for antibacterial therapy and safeguarding diabetic osseointegration.

Diabetic infectious microenvironment (DIME) frequently leads to a critical failure of osseointegration by virtue of its main peculiarities including typical hyperglycemia and pathogenic infection around implants. To address the plaguing issue, we devise a glucose-primed orthopedic implant composed of polyetheretherketone (PEEK), Cu-chelated metal-polyphenol network (hauberk coating) and glucose oxidase (GOx) for boosting diabetic osseointegration. Upon DIME, GOx on implants sostenuto consumes glucose to generate H2O2, and Cu liberated from hauberk coating catalyzes the H2O2 to highly germicidal •OH, which massacres pathogenic bacteria through photo-augmented chemodynamic therapy. Intriguingly, the catalytic efficiency of the coating gets greatly improved with the turnover number (TON) of 0.284 s-1. Moreover, the engineered implants exhibit satisfactory cytocompatibility and facilitate osteogenicity due to the presence of Cu and osteopromotive polydopamine coating. RNA-seq analysis reveals that the implants enable to combat infections and suppress pro-inflammatory phenotype (M1). Besides, in vivo evaluations utilizing infected diabetic rat bone defect models at week 4 and 8 authenticate that the engineered implants considerably elevate osseointegration through pathogen elimination, inflammation dampening and osteogenesis promotion. Altogether, our present study puts forward a conceptually new tactic that arms orthopedic implants with glucose-primed antibacterial and osteogenic capacities for intractable diabetic osseointegration.