Improvements of Corrosion Resistance and Antibacterial Properties of Hydroxyapatite/Cupric Oxide Doped Titania Composite Coatings on Degradable Magnesium Alloys.

The excellent biocompatibility of calcium phosphate (CaP) coatings makes them widely used in magnesium (Mg) alloy orthopedic implant materials. However, the porous morphology of CaP coatings limits their corrosion resistance. A cupric oxide (CuO) doped titania (TiO2) sol-gel coating is prepared on a porous hydroxyapatite (HA) coating. According to electrochemical test results, the HA/CuO-TiO2 coating obtains a current density of 6 × 10-4 mA/cm2, lower than that of the Mg alloy (2.6 × 10-2 mA/cm2). The hydrogen evaluation of the HA/CuO-TiO2 coating is only 1/12 that of the Mg alloy after immersion for 7 days. In addition, the HA/CuO-TiO2 coating has an antibacterial rate of 99.5 ± 0.4% against Staphylococcus aureus, significantly higher than that of the HA coating (19.8 ± 0.3%) and HTC0 coating (38.4 ± 0.5%). The CuO doped composite coating has no adverse effect or cytotoxicity on cell proliferation (cell viability ≥79.6%). Hence, the HA/CuO-TiO2 composite coating is useful for enhancing the corrosion resistance and antibacterial properties of Mg alloys while ensuring cytocompatibility. The HA/CuO-TiO2 coated AZ60 Mg alloy can meet the requirements of clinical application.

Nanophotonics-enabled solar membrane distillation for off-grid water purification.

With more than a billion people lacking accessible drinking water, there is a critical need to convert nonpotable sources such as seawater to water suitable for human use. However, energy requirements of desalination plants account for half their operating costs, so alternative, lower energy approaches are equally critical. Membrane distillation (MD) has shown potential due to its low operating temperature and pressure requirements, but the requirement of heating the input water makes it energy intensive. Here, we demonstrate nanophotonics-enabled solar membrane distillation (NESMD), where highly localized photothermal heating induced by solar illumination alone drives the distillation process, entirely eliminating the requirement of heating the input water. Unlike MD, NESMD can be scaled to larger systems and shows increased efficiencies with decreased input flow velocities. Along with its increased efficiency at higher ambient temperatures, these properties all point to NESMD as a promising solution for household- or community-scale desalination.

Tat/HA2 Peptides Conjugated AuNR@pNIPAAm as a Photosensitizer Carrier for Near Infrared Triggered Photodynamic Therapy.

To achieve an efficiency of intracellular photosensitizers (PSs) delivery and efficacy of photodynamic therapy, we have developed a novel class of PS formulation for encapsulating sulfonated aluminum phthalocyanine (AlPcS4) by taking advantage of the membrane-disruptive peptides Tat/HA2 and the photothermally triggered delivery system using AuNR@pNIPAAm. The coordinated effects of cell penetrating peptide Tat and fusogenic peptide HA2 could enhance the efficient cellular internalization and endo/lysosome escape of PSs delivery systems. Singlet oxygen generation was inhibited due to the reaction between loaded AlPcS4 and Au nanorods, which indicated that the AlPcS4-loaded, AuNR@pNIPAAm delivery system might be nonphototoxic in the circulatory system. However, this PSs-loaded nanosystem became highly phototoxic as it underwent the near-infrared irradiation by using the combined lights of 808 and 680 nm. Upon irradiation, the Tat/HA2 conjugated AuNR@pNIPAAm-Pc elicited an active photodynamic response against the cancer cells, leading to effective cells killing via mitochondria-associated apoptotic pathway. This study also demonstrated improved PDT therapeutic efficacy after intravenous administration of Tat/HA2-AuNR@pNIPAAm-Pc and the subsequent lights irradiations in tumor-bearing mice. We describe here a strategy for enhanced photodynamic eradication of solid tumors by endo/lysosomal escape and highlight the great promise of peptide-based nanocarriers used for cancer therapy.

Fluoride releasing in polymer blends of poly(ethylene oxide) and poly(methyl methacrylate).

Introduction: Polymethyl methacrylate is a polymer commonly used in clinical dentistry, including denture bases, occlusal splints and orthodontic retainers. Methods: To augment the polymethyl methacrylate-based dental appliances in counteracting dental caries, we designed a polymer blend film composed of polymethyl methacrylate and polyethylene oxide by solution casting and added sodium fluoride. Results: Polyethylene oxide facilitated the dispersion of sodium fluoride, decreased the surface average roughness, and positively influenced the hydrophilicity of the films. The blend film made of polymethyl methacrylate, polyethylene oxide and NaF with a mass ratio of 10: 1: 0.3 showed sustained release of fluoride ions and acceptable cytotoxicity. Antibacterial activity of all the films to Streptococcus mutans was negligible. Discussion: This study demonstrated that the polymer blends of polyethylene oxide and polymethyl methacrylate could realize the relatively steady release of fluoride ions with high biocompatibility. This strategy has promising potential to endow dental appliances with anti-cariogenicity.

An Injectable Black Phosphorus Hydrogel for Rapid Tooth Extraction Socket Healing.

The excess production of reactive oxygen species (ROS) will delay tooth extraction socket (TES) healing. In this study, we developed an injectable thermosensitive hydrogel (NBP@BP@CS) used to treat TES healing. The hydrogel formulation incorporated black phosphorus (BP) nanoflakes, recognized for their accelerated alveolar bone regeneration and ROS-scavenging properties, and dl-3-n-butylphthalide (NBP), a vasodilator aimed at enhancing angiogenesis. In vivo investigations strongly demonstrated that NBP@BP@CS improved TES healing due to antioxidation and promotion of alveolar bone regeneration by BP nanoflakes. The sustained release of NBP from the hydrogel promoted neovascularization and vascular remodeling. Our results demonstrated that the designed thermosensitive hydrogel provided great opportunity not only for ROS elimination but also for the promotion of osteogenesis and angiogenesis, reflecting the "three birds with one stone" concept, and has tremendous potential for rapid TES healing.

Injectable Thermosensitive Gel CH-BPNs-NBP for Effective Periodontitis Treatment through ROS-Scavenging and Jaw Vascular Unit Protection.

Periodontitis, a prevalent inflammatory condition in the oral cavity, is closely associated with oxidative stress-induced tissue damage mediated by excessive reactive oxygen species (ROS) production. The jaw vascular unit (JVU), encompassing both vascular and lymphatic vessels, plays a crucial role in maintaining tissue fluid homeostasis and contributes to the pathological process in inflammatory diseases of the jaw. This study presents a novel approach for treating periodontitis through the development of an injectable thermosensitive gel (CH-BPNs-NBP). The gel formulation incorporates black phosphorus nanosheets (BPNs), which are notable for their ROS-scavenging properties, and dl-3-n-butylphthalide (NBP), a vasodilator that promotes lymphatic vessel function within the JVU. These results demonstrate that the designed thermosensitive gel serve as a controlled release system, delivering BPNs and NBP to the site of inflammation. CH-BPNs-NBP not only protects macrophages and human lymphatic endothelial cells from ROS attack but also promotes M2 polarization and lymphatic function. In in vivo studies, this work observes a significant reduction in inflammation and tissue damage, accompanied by a notable promotion of alveolar bone regeneration. This research introduces a promising therapeutic strategy for periodontitis, leveraging the unique properties of BPNs and NBP within an injectable thermosensitive gel.

NLRP3 Regulates Mandibular Healing through Interaction with UCHL5 in MSCs.

NLRP3 has been involved in several physiological and pathological processes. However, the role and mechanism of NLRP3 activation in mandibular healing remain unclear. Here, a full-thickness mandibular defect model by osteotomy was established in wild-type (WT) and Prx1-Cre/ROSAnTnG mice to demonstrate the NLRP3 inflammasome activation in mandibular healing. We found that NLRP3 was activated in mesenchymal stem cells (MSCs)-mediated mandibular healing and was prominent in Prx1+ cells. Inhibition of NLRP3 exerted a positive effect on bone formation without changing the number of Prx1-cre+ cells in the defect areas. In addition, NLRP3 deficiency promoted osteoblast differentiation. We next screened for the deubiquitinating enzymes that were previously reported to be associated with NLRP3, and identified UCHL5 as a regulator of NLRP3 activation in mandibular healing. Mechanistically, NLRP3 directly bound to UCHL5 and maintained its stability through reducing ubiquitin-proteasome pathway degradation in mandibular MSCs. At last, UCHL5 inhibition enhanced osteoblast differentiation by promoting NLRP3 ubiquitination and degradation. Thus, our results provided the proof that NLRP3 acted as a negative modulator in mandibular healing and extended the current knowledge regarding posttranslational modification of NLRP3 by UCHL5.

Stearic Acid Treatment Enhancing Corrosion Resistance of Biomimetic-Deposited Calcium Phosphate Dihydrate Coating on Medical Degradable Magnesium Alloy.

Magnesium (Mg) alloys, a degradable material, have been studied for medical applications due to their excellent mechanical and chemical properties. However, their applications are limited by rapid corrosion. In this work, stearic acid and sodium stearate were used to treat the silane-induced calcium phosphate dihydrate coating to improve its protection for the Mg alloy further without changing the bone-like structure of calcium phosphate. The different effects of stearic acid treatment and sodium stearate treatment were compared. Electrochemical test and immersion test results confirmed that the corrosion resistance of the stearic acid-treated composite coating was greatly enhanced with a reduced corrosion current density by 3 orders of magnitude and hydrogen evolution reduced to 1/25 after 14 days. The stearic acid-treated coating also exhibited improved in vitro biocompatibility corroborated by promoted cell viability and better cell morphology.

In vitro and in vivo studies on gelatin-siloxane nanoparticles conjugated with SynB peptide to increase drug delivery to the brain.

BACKGROUND: Nanobiotechnology can provide more efficient tools for diagnosis, targeted and personalized therapy, and increase the chances of brain tumor treatment being successful. Use of nanoparticles is a promising strategy for overcoming the blood-brain barrier and delivering drugs to the brain. Gelatin-siloxane (GS) nanoparticles modified with Tat peptide can enhance plasmid DNA transfection efficiency compared with a commercial reagent. METHODS: SynB-PEG-GS nanoparticles are membrane-penetrable, and can cross the blood-brain barrier and deliver a drug to its target site in the brain. The efficiency of delivery was investigated in vivo and in vitro using brain capillary endothelial cells, a cocultured blood-brain barrier model, and a normal mouse model. RESULTS: Our study demonstrated that both SynB-PEG-GS and PEG-GS nanoparticles had a spherical shape and an average diameter of 150-200 nm. It was shown by MTT assay that SynB-PEG-GS nanoparticles had good biocompatibility with brain capillary endothelial cells. Cellular uptake by SynB-PEG-GS nanoparticles was higher than that for PEG-GS nanoparticles for all incubation periods. The amount of SynB-PEG-GS nanoparticles crossing the cocultured blood-brain barrier model was significantly higher than that of PEG-GS nanoparticles at all time points measured (P < 0.05). In animal testing, SynB-PEG-GS nanoparticle levels in the brain were significantly higher than those of PEG-GS nanoparticles at all time points measured (P < 0.01). In contrast with localization in the brain, PEG-GS nanoparticle levels were significantly higher than those of SynB-PEG-GS nanoparticles (P < 0.01) in the liver. CONCLUSION: This study indicates that SynB-PEG-GS nanoparticles have favorable properties with regard to morphology, size distribution, and toxicity. Moreover, the SynB-PEG-GS nanoparticles exhibited more efficient brain capillary endothelial cell uptake and improved crossing of the blood-brain barrier. Further, biodistribution studies of rhodamine-loaded nanoparticles demonstrated that modification with the SynB peptide could not only improve the ability of PEG-GS nanoparticles to evade capture in the reticuloendothelial system but also enhance their efficiency in crossing the blood-brain barrier.

Multifunctional ZnPc-loaded mesoporous silica nanoparticles for enhancement of photodynamic therapy efficacy by endolysosomal escape.

The cellular uptake and localization of photosensitizer-loaded nanoparticles have significant impact on photodynamic therapy (PDT) efficacy due to short lifetime and limited action radius of singlet oxygen. Herein, we develop poly(ethylene glycol) (PEG)- and polyethylenimine (PEI)-functionalized zinc(II) phthalocyanine (ZnPc)-loaded mesoporous silica nanoparticles (MSNs), which are able to distribute in the cytosol by endolysosomal escape. In this photosensitizer-carrier system (PEG-PEI-MSNs/ZnPc), ZnPc is a PDT agent; MSNs are the nanocarrier for encapsulating ZnPc; PEI facilitates endosomal escape; and PEG enhances biocompatibility. The as-synthesized PEG-PEI-MSNs/ZnPc have a high escape efficiency from the lysosome to the cytosol due to the "proton sponge" effect of PEI. Compared with the ZnPc-loaded MSNs, the phototoxicity of the PEG-PEI-MSNs/ZnPc is greatly enhanced in vitro. By measuring the mitochondrial membrane potential, a significant loss of >80% Δψm after treatment with PEG-PEI-MSNs/ZnPc-PDT is observed. It is further demonstrated that the ultra-efficient passive tumor targeting and excellent PDT efficacy are achieved in tumor-bearing mice upon intravenous injection of PEG-PEI-MSNs/ZnPc and the followed light exposure. We present here a strategy for enhancement of PDT efficacy by endolysosomal escape and highlight the promise of using multifunctional MSNs for cancer therapy.