Multifunctional antibacterial bioactive nanoglass hydrogel for normal and MRSA infected wound repair.

Large-scale skin damage brings potential risk to patients, such as imbalance of skin homeostasis, inflammation, fluid loss and bacterial infection. Moreover, multidrug resistant bacteria (MDRB) infection is still a great challenge for skin damage repair. Herein, we developed an injectable self-healing bioactive nanoglass hydrogel (FABA) with robust antibacterial and anti-inflammatory ability for normal and Methicillin-resistant Staphylococcus aureus (MRSA) infected skin wound repair. FABA hydrogel was fabricated facilely by the self-crosslinking of F127-CHO (FA) and alendronate sodium (AL)-decorated Si-Ca-Cu nanoglass (BA). FABA hydrogel could significantly inhibit the growth of Staphylococcus aureus, Escherichia coli and MRSA in vitro, while showing good cytocompatibility and hemocompatibility. In addition, FABA hydrogel could inhibit the expression of proinflammatory factor TNF-α and enhance the expression of anti-inflammatory factor IL-4/ IL-10. Based on its versatility, FABA hydrogel could complete wound closure efficiently (75% at day 3 for normal wound, 70% at day 3 for MRSA wound), which was almost 3 times higher than control wound, which was related with the decrease of inflammatory factor in early wound. This work suggested that FABA hydrogel could be a promising dressing for acute and MRSA-infected wound repair.

Bioactive anti-inflammatory antibacterial metformin-contained hydrogel dressing accelerating wound healing.

Highly efficient wound healing and skin regeneration remain a challenge. Long-term inflammation and bacterial infection can inhibit the healing process and lead to the scar formation. Here, we report a hydrogel (FEM) formed by self-assembly of ε-poly-l-lysine-F127-ε-poly-l-lysine (EPL-F127-EPL) and metformin for wound repair. Especially, the role of metformin-based antibacterial hydrogel in wound healing and repair was investigated for the first time. FEM has inherent multifunctional properties, including controlled metformin release, anti-inflammatory and antibacterial activity, temperature responsiveness, injectable and self-healing capabilities. The in vivo results showed that FEM dressings accelerated the wound healing by stimulating the angiogenesis process of the wound tissue and anti-inflammation. This study shows that the multifunctional metformin-contained hydrogel scaffolds could enhance the wound repair through the anti-inflammation and accelerated angiogenesis, which could also expand the biomedical applications of metformin-based biomaterials.

Oral Gene Therapy of HFD-Obesity via Nonpathogenic Yeast Microcapsules Mediated shRNA Delivery.

Obesity is a chronic systemic inflammatory disease, which occurs when energy intake exceeds the energy consumption. Therefore, controlling energy intake or increasing physical consumption can effectively control obesity. However, in reality, it is very difficult for the majority of obese patients to lose weight by autonomously controlling diet. In this study, oral shRNA/yeast microcapsules were constructed with non-virus-mediated IL-1ß shRNA interference vectors and non-pathogenic Saccharomyces cerevisiae. Moreover, high-fat diet induced obese mice were established to assess the weight loss effect of IL-1ß shRNA/yeast microcapsules via the oral route. After IL-1ß shRNA/yeast treatment, body weight and fat weight was reduced. Compared with the control group, higher average food intake but lower energy conversion rate was observed in IL-1ß shRNA/yeast group. In addition, lipid metabolism related cytokines and blood glucose concentration in the circulating blood was improved after IL-1ß shRNA/yeast treatment. Yeast microcapsules mediated IL-1ß shRNA delivery can effectively improve obesity. Noteworthy, this kind of non-diet-controlled weight loss strategy does not need diet control, and shows good biocompatibility. It is good news to obese patients who need to lose weight but cannot control their diet.

Multifunctional Protein-Decorated Bioactive Glass Nanoparticles for Tumor-Specific Therapy and Bioimaging In Vitro and In Vivo.

Multifunctional nanocarriers with a simple structure and biocompatibility for bioimaging, potential tumor targeting, and precise antitumor ability are promising in cancer therapy. Bioactive glass is an important biomaterial and has been used in clinical bone tissue repair due to the high biocompatibility and bioactivity. Herein, we report fetal bovine serum (FBS)-decorated europium-doped bioactive glass nanoparticles (EuBGN@FBS) with excellent biosafety and enhanced tumor targeting for cancer imaging and therapy. EuBGN@FBS showed the controlled photoluminescent properties and pH-responsive anticancer drug release behavior. The FBS decoration significantly enhanced the dispersibility in physiological medium and improved hemocompatibility and cellular uptake of EuBGN. Relative to EuBGN, EuBGN@FBS could also efficiently image the cancer cell and show significantly enhanced targeted tumor imaging and chemotherapy in vivo while retaining negligible side effects. The simple and biocompatible structure with efficient tumor targeting, imaging, and therapy makes EuBGN@FBS highly promising in future cancer therapy.

Bioactive antiinflammatory antibacterial hemostatic citrate-based dressing with macrophage polarization regulation for accelerating wound healing and hair follicle neogenesis.

The efficient cutaneous wound healing accompanied with the enhanced skin appendage regeneration is still a challenge. The bacterial infection and excessive/prolonged inflammation inhibit wound healing process and result in the scar formation. Herein, we reported an anti-inflammatory polycitrate-polyethyleneimine-Ibuprofen (PCEI) and multifunctional PCEI-based F127-ε-polypeptide-alginic (FEA) dressing (FEA-PCEI) for accelerating wound healing and hair follicle neogenesis. PCEI showed the excellent anti-inflammation function through stimulating macrophage towards anti-inflammatory M2 subtype polarization. The FEA-PCEI dressing showed the temperature-response gelation, injectability, robust antibacterial activity, light-damage-resistant, homeostasis ability, and good cytocompatibility. The optimized dosage of FEA-PCEI dressing could significantly accelerate wound healing with anti-infection ability, reduce the scar formation, and promote the hair follicle neogenesis. This study provided a wound-repairing strategy through regulating the phenotype of immune cells by the designing bioactive multifunctional biomaterials.

Yeast Cell wall Particle mediated Nanotube-RNA delivery system loaded with miR365 Antagomir for Post-traumatic Osteoarthritis Therapy via Oral Route.

Post-traumatic osteoarthritis (PTOA) is an acute injury-induced joint inflammation followed by a gradual degradation of articular cartilage. However, there is no FDA-approved Disease-Modifying Osteoarthritis Drug currently. Although gene therapy with microRNA can improve PTOA progression, there is no effective gene delivery vehicle for orally deliver therapeutics due to the harsh environment of the gastrointestinal tract. In this study, we investigated the effect of yeast cell wall particle (YCWP) mediated nanotube-RNA delivery system on PTOA therapy via oral route. Methods: Nontoxic and degradable AAT and miRNA365 antagomir was self-assembled into miR365 antagomir/AAT (NPs). Then NPs-YCWP oral drug delivery system was constructed by using NPs and non-pathogenic YCWP which can be specifically recognized by macrophages. Moreover, surgical destabilization of the medial meniscus induced PTOA mice model was established to evaluate the therapeutic effect of NPs-YCWP via oral route. Results: Compared with control group, NPs showed higher gene inhibition efficiency both in chondrogenic cell line and primary chondrocytes in vitro. Treatment of macrophages with fluorescently labeled NPs-YCWP, the results showed that NPs-YCWP was successfully engulfed by macrophages and participated in the regulation of gene expression in vitro. Under the protection of YCWP, miR365 antagomir/AAT passes through the gastrointestinal tract without degradation after oral administration. After NPs-YCWP therapy, the results of histological staining, gene and protein expression showed that miR365 antagomir/NPs-YCWP improved the symptom of PTOA. Conclusion: Here, we constructed a biodegradable drug delivery system based on non-pathogenic YCWP and nanotubes, which can be used for PTOA therapy via the oral route. It suggests a new gene therapy strategy with YCWP mediated oral nano drug delivery system may serve as a platform for joint degeneration treatment.

Modeling and control of a novel X-Y parallel piezoelectric-actuator driven nanopositioner.

In this paper, a novel X-Y parallel piezoelectric-actuator driven nanopositioner is studied from the perspectives of design optimization, dynamical modeling, as well as controller synthesis for high precision positioning. FEM (Finite Element Method) and dynamical modeling are provided to analyze the mechatronic structure of the proposed two-dimensional nano-stage, where the system model, including the hysteresis loop, is derived analytically and further verified experimentally. A robust control architecture incorporating an H∞ controller and an anti-windup compensator is then developed to deal with the hysteresis and saturation nonlinearities of the piezoelectric actuators. Real time experiments on the nano-stage platform demonstrate good robustness, high precision positioning and tracking performance, as well as recovery speed in the presence of saturation.