Total hip arthroplasty with porous tantalum trabecular metal pads in patients with Crowe IV developmental dysplasia of the hip: a midterm followup study.

PURPOSE: Crowe IV developmental dysplasia of the hip (DDH) is a catastrophic hip disease. Moreover, obtaining ideal clinical efficacy in conventional total hip arthroplasty (THA) is often difficult. In this study, we aimed to assess the mid-term clinical results of THA with porous tantalum trabecular metal (TM) pads for acetabular reconstruction in the treatment of Crowe IV DDH. METHODS: A cohort of 28 patients (32 hips) diagnosed with Crowe type IV DDH who underwent acetabular reconstruction during THA using TM pads with scheduled follow-up between 2011 and 2018, were included in this study. Eight cases were men and 24 were women, with a mean age of 48.4 years (range, 36-72 years) and a mean follow-up was 74.3 months (range, 42-132 months). All patients underwent acetabular reconstruction using TM pads and total hip replacement with subtrochanteric osteotomy. RESULTS: At the final follow-up, 28 hips (87.5%) demonstrated mild or no postoperative limping. The Harris Hip Score improved from 58.4 ± 10.6 preoperatively to 85.6 ± 8.9. The mean pain, stiffness, and function scores on the Western Ontario and McMaster University Osteoarthritis index were 86.5 ± 10.2, 87.3 ± 12.4 and 85.4 ± 11.6 respectively. The mean score of patient satisfaction was 90.4 ± 7.6. Additionally, the SF-12 physical summary score was 41.8 ± 5.6 and the SF-12 mental summary score was 51.6 ± 5.4. TM construct survivorship due to all-cause failure was 90.6% at 5 years with 3 hips at risk, 87.5% at 10 years with 4 hips at risk. The survivorship due to failure from aseptic loosening was 96.9% at 5 years with 1hips at risk and 93.75% at 10 years with 2 hips at risk. CONCLUSION: This study demonstrated satisfactory mid-term clinical and radiological results with the application of TM pads for acetabular reconstruction combined with THA in patients with Crowe IV DDH. TRIAL REGISTRATION NUMBER: ChiCTR1800014526, Date: 18/01/2018.

Electrochemical chiral sensor for recognition of amino acid enantiomers with cyclodextrin-based microporous organic networks.

BACKGROUND: Chirality is a ubiquitous phenomenon in nature, but enantiomers exhibit different pharmacological activities and toxicological effects. Therefore, Chiral recognition plays a pivotal role in various fields such as life sciences, chemical synthesis, drug development, and materials science. The synthesis of novel chiral composites with well-defined loading capabilities and ordered structures holds significant potential for electrochemical chiral recognition applications. However, the design of selective and stable electrochemical chiral recognition materials remains a challenging task. RESULT: In this work, we construct a simple and rapid electrochemical sensing platform for tryptophan (Trp) enantiomer recognition using cyclodextrin-modified microporous organic network as chiral recognition agent. CD-MON with chiral microenvironment was prepared by Sonogashira-Hagihara coupling reaction of the chiral molecule heptyl-6-iodo-6-deoxyß-cyclodextrin and 1, 4-Diethynylbenzene. The adhesion of BSA makes CD-MON firmly fixed on the electrode surface, and as a chiral protein, it can improve the chiral recognition ability through synergistic effect. Chiral amino acids are in full contact with the chiral microenvironment during pore conduction of MON, and L-Trp is more stably bound to CD-MON/BSA due to steric hindrance, host-guest recognition and hydrogen bonding. Therefore, the electrochemical sensor can effectively identify tryptophan enantiomers (IL-Trp/ID-Trp = 2.02), and it exhibits a detection limit of 2.6 µM for L-Trp. UV-Vis spectroscopy confirmed the adsorption capacity of CD-MON towards tryptophan enantiomers in agreement with electrochemistry results. SIGNIFICANCE: The prepared chiral sensor has excellent stability, reproducibility (RSD = 3.7%) and selectivity, realizes the quantitative detection of single isomer in tryptophan racemic and quantitative analysis in real samples with 94.0%-101.0% recovery. This work represents the first application of MON in chiral electrochemistry which expands the application scope of chiral sensors and holds great significance in separation science and electrochemical sensing.

Structurally and mechanically tuned macroporous hydrogels for scalable mesenchymal stem cell-extracellular matrix spheroid production.

Mesenchymal stem cells (MSCs) are essential in regenerative medicine. However, conventional expansion and harvesting methods often fail to maintain the essential extracellular matrix (ECM) components, which are crucial for their functionality and efficacy in therapeutic applications. Here, we introduce a bone marrow-inspired macroporous hydrogel designed for the large-scale production of MSC-ECM spheroids. Through a soft-templating approach leveraging liquid-liquid phase separation, we engineer macroporous hydrogels with customizable features, including pore size, stiffness, bioactive ligand distribution, and enzyme-responsive degradability. These tailored environments are conducive to optimal MSC proliferation and ease of harvesting. We find that soft hydrogels enhance mechanotransduction in MSCs, establishing a standard for hydrogel-based 3D cell culture. Within these hydrogels, MSCs exist as both cohesive spheroids, preserving their innate vitality, and as migrating entities that actively secrete functional ECM proteins. Additionally, we also introduce a gentle, enzymatic harvesting method that breaks down the hydrogels, allowing MSCs and secreted ECM to naturally form MSC-ECM spheroids. These spheroids display heightened stemness and differentiation capacity, mirroring the benefits of a native ECM milieu. Our research underscores the significance of sophisticated materials design in nurturing distinct MSC subpopulations, facilitating the generation of MSC-ECM spheroids with enhanced therapeutic potential.

Application of metal-organic frameworks in infectious wound healing.

Metal-organic frameworks (MOFs) are metal-organic skeleton compounds composed of self-assembled metal ions or clusters and organic ligands. MOF materials often have porous structures, high specific surface areas, uniform and adjustable pores, high surface activity and easy modification and have a wide range of prospects for application. MOFs have been widely used. In recent years, with the continuous expansion of MOF materials, they have also achieved remarkable results in the field of antimicrobial agents. In this review, the structural composition and synthetic modification of MOF materials are introduced in detail, and the antimicrobial mechanisms and applications of these materials in the healing of infected wounds are described. Moreover, the opportunities and challenges encountered in the development of MOF materials are presented, and we expect that additional MOF materials with high biosafety and efficient antimicrobial capacity will be developed in the future.

In vitro and in vivo dissolution of biocompatible S59 glass scaffolds.

Fabrication of porous tissue-engineering scaffolds from bioactive glasses (BAG) is complicated by the tendency of BAG compositions to crystallize in thermal treatments during scaffold manufacture. Here, experimental biocompatible glass S59 (SiO2 59.7 wt%, Na2O 25.5 wt%, CaO 11.0 wt%, P2O5 2.5 wt%, B2O3 1.3 wt%), known to be resistant to crystallization, was used in sintering of glass granules (300-500 µm) into porous scaffolds. The dissolution behavior of the scaffolds was then studied in vivo in rabbit femurs and under continuous flow conditions in vitro (14 days in vitro/56 days in vivo). The scaffolds were osteoconductive in vivo, as bone could grow into the scaffold structure. Still, the scaffolds could not induce sufficiently rapid bone ingrowth to replace the strength lost due to dissolution. The scaffolds lost their structure and strength as the scaffold necks dissolved. In vitro, S59 dissolved congruently throughout the 14-day experiments, resulting in only a slight reaction layer formation. Manufacturing BAG scaffolds from S59 that retain their amorphous structure was thus possible. The relatively rapid and stable dissolution of the scaffold implies that the glass S59 may have the potential to be used in composite implants providing initial strength and stable, predictable release of ions over longer exposure times.

Preparation of Microsponge Drug Delivery System (MSDDS) Followed by a Scale-Up Approach.

In 1987, Won invented the solid-phase porous microsphere (MS), which stores bioactive compounds in many interconnected voids. Spherical particles (5-300 µm), MS, may form clusters of smaller spheres, resulting in many benefits. The current investigation focussed on gel-encased formulation, which can be suitable for dermal usage. First, quasi-emulsion (w/o/w) solvent evaporation was used to prepare 5-fluorouracil (5 FU) MS particles. The final product was characterized (SEM shows porous structure, FTIR and DSC showed drug compatibility with excipients, and gel formulation is shear-thinning) and further scaled up using the 8-fold method. Furthermore, CCD (Central Composite Design) was implemented to obtain the optimized results. After optimizing the conditions, including the polymer (600 mg, ethyl cellulose (EC), eudragit RS 100 (ERS)), stirring speed (1197 rpm), and surfactant concentration (2% w/v), we achieved the following results: optimal yield (63%), mean particle size (152 µm), drug entrapment efficiency (76%), and cumulative drug release (74.24% within 8 h). These findings are promising for industrial applications and align with the objectives outlined in UN Sustainable Development Goals 3, 9, and 17, as well as the goals of the G20 initiative.

pH-Responsive Mesoporous Silica Nanoparticles Loaded with Naringin for Targeted Osteoclast Inhibition and Bone Regeneration.

Background: It is well-established that osteoclast activity is significantly influenced by fluctuations in intracellular pH. Consequently, a pH-sensitive gated nano-drug delivery system represents a promising therapeutic approach to mitigate osteoclast overactivity. Our prior research indicated that naringin, a natural flavonoid, effectively mitigates osteoclast activity. However, naringin showed low oral availability and short half-life, which hinders its clinical application. We developed a drug delivery system wherein chitosan, as gatekeepers, coats mesoporous silica nanoparticles loaded with naringin (CS@MSNs-Naringin). However, the inhibitory effects of CS@MSNs-Naringin on osteoclasts and the underlying mechanisms remain unclear, warranting further research. Methods: First, we synthesized CS@MSNs-Naringin and conducted a comprehensive characterization. We also measured drug release rates in a pH gradient solution and verified its biosafety. Subsequently, we investigated the impact of CS@MSNs-Naringin on osteoclasts induced by bone marrow-derived macrophages, focusing on differentiation and bone resorption activity while exploring potential mechanisms. Finally, we established a rat model of bilateral critical-sized calvarial bone defects, in which CS@MSNs-Naringin was dispersed in GelMA hydrogel to achieve in situ drug delivery. We observed the ability of CS@MSNs-Naringin to promote bone regeneration and inhibit osteoclast activity in vivo. Results: CS@MSNs-Naringin exhibited high uniformity and dispersity, low cytotoxicity (concentration≤120 µg/mL), and significant pH sensitivity. In vitro, compared to Naringin and MSNs-Naringin, CS@MSNs-Naringin more effectively inhibited the formation and bone resorption activity of osteoclasts. This effect was accompanied by decreased phosphorylation of key factors in the NF-κB and MAPK signaling pathways, increased apoptosis levels, and a subsequent reduction in the production of osteoclast-specific genes and proteins. In vivo, CS@MSNs-Naringin outperformed Naringin and MSNs-Naringin, promoting new bone formation while inhibiting osteoclast activity to a greater extent. Conclusion: Our research suggested that CS@MSNs-Naringin exhibited the strikingly ability to anti-osteoclasts in vitro and in vivo, moreover promoted bone regeneration in the calvarial bone defect.

Mesoporous Silicon with Strontium-Powered Poly(Lactic-Co-Glycolic acid)/Gelatin-Based Dressings Facilitate Skin Tissue Repair.

Purpose: Functional inorganic nanomaterials (NMs) are widely exploited as bioactive materials and drug depots. The lack of a stable form of application of NMs at the site of skin injury, may impede the removal of the debridement, elevate pH, induce tissue toxicity, and limit their use in skin repair. This necessitates the advent of innovative wound dressings that overcome the above limitations. The overarching objective of this study was to exploit strontium-doped mesoporous silicon particles (PSiSr) to impart multifunctionality to poly(lactic-co-glycolic acid)/gelatin (PG)-based fibrous dressings (PG@PSiSr) for excisional wound management. Methods: Mesoporous silicon particles (PSi) and PSiSr were synthesized using a chemo-synthetic approach. Both PSi and PSiSr were incorporated into PG fibers using electrospinning. A series of structure, morphology, pore size distribution, and cumulative pH studies on the PG@PSi and PG@PSiSr membranes were performed. Cytocompatibility, hemocompatibility, transwell migration, scratch wound healing, and delineated angiogenic properties of these composite dressings were tested in vitro. The biocompatibility of composite dressings in vivo was assessed by a subcutaneous implantation model of rats, while their potential for wound healing was discerned by implantation in a full-thickness excisional defect model of rats. Results: The PG@PSiSr membranes can afford the sustained release of silicon ions (Si4+) and strontium ions (Sr2+) for up to 192 h as well as remarkably promote human umbilical vein endothelial cells (HUVECs) and NIH-3T3 fibroblasts migration. The PG@PSiSr membranes also showed better cytocompatibility, hemocompatibility, and significant formation of tubule-like networks of HUVECs in vitro. Moreover, PG@PSiSr membranes also facilitated the infiltration of host cells and promoted the deposition of collagen while reducing the accumulation of inflammatory cells in a subcutaneous implantation model in rats as assessed for up to day 14. Further evaluation of membranes transplanted in a full-thickness excisional wound model in rats showed rapid wound closure (PG@SiSr vs control, 96.1% vs 71.7%), re-epithelialization, and less inflammatory response alongside skin appendages formation (eg, blood vessels, glands, hair follicles, etc.). Conclusion: To sum up, we successfully fabricated PSiSr particles and prepared PG@PSiSr dressings using electrospinning. The PSiSr-mediated release of therapeutic ions, such as Si4+ and Sr2+, may improve the functionality of PLGA/Gel dressings for an effective wound repair, which may also have implications for the other soft tissue repair disciplines.

Dual-recognition colorimetric platform based on porous Au@Pt nanozymes for highly sensitive washing-free detection of Staphylococcus aureus.

A dual-recognition strategy is reported to construct a one-step washing and highly efficient signal-transduction tag system for high-sensitivity colorimetric detection of Staphylococcus aureus (S. aureus). The porous (gold core)@(platinum shell) nanozymes (Au@PtNEs) as the signal labels show highly efficient peroxidase mimetic activity and are robust. For the sake of simplicity the detection involved the use of a vancomycin-immobilized magnetic bead (MB) and aptamer-functionalized Au@PtNEs for dual-recognition detection in the presence of S. aureus. In addition, we designed a magnetic plate to fit the 96-well microplate to ensure consistent magnetic properties of each well, which can quickly remove unreacted Au@PtNEs and sample matrix while avoiding tedious washing steps. Subsequently, Au@PtNEs catalyze hydrogen peroxide (H2O2) to oxidize 3,3',5,5'-tetramethylbenzidine (TMB) generating a color signal. Finally, the developed Au@PtNEs-based dual-recognition washing-free colorimetric assay displayed a response in the range of S. aureus of 5 × 101-5 × 105 CFU/mL, and the detection limit was 40 CFU/mL within 1.5 h. In addition, S. aureus-fortified samples were analyzed to further evaluate the performance of the proposed method, which yielded average recoveries ranging from 93.66 to 112.44% and coefficients of variation (CVs) within the range 2.72-9.01%. These results furnish a novel horizon for the exploitation of a different mode of recognition and inexpensive enzyme-free assay platforms as an alternative to traditional enzyme-based immunoassays for the detection of other Gram-positive pathogenic bacteria.

Pore-spanning membranes as a tool to investigate lateral lipid membrane heterogeneity.

Over the years, it has become more and more obvious that lipid membranes show a very complex behavior. This behavior arises in part from the large number of different kinds of lipids and proteins and how they dynamically interact with each other. In vitro studies using artificial membrane systems have shed light on the heterogeneity based on lipid-lipid interactions in multicomponent bilayer mixtures. Inspired by the raft hypothesis, the coexistence of liquid-disordered (ld) and liquid-ordered (lo) phases has drawn much attention. It was shown that ternary lipid mixtures containing low- and high-melting temperature lipids and cholesterol can phase separate into a lo phase enriched in the high-melting lipids and cholesterol and a ld phase enriched in the low-melting lipids. Depending on the model membrane system under investigation, different domain sizes, shapes, and mobilities have been found. Here, we describe how to generate phase-separated lo/ld phases in model membrane systems termed pore-spanning membranes (PSMs). These PSMs are prepared on porous silicon substrates with pore sizes in the micrometer regime. A proper functionalization of the top surface of the substrates is required to achieve the spreading of giant unilamellar vesicles (GUVs) to obtain PSMs. Starting with lo/ld phase-separated GUVs lead to membrane heterogeneities in the PSMs. Depending on the functionalization strategy of the top surface of the silicon substrate, different membrane heterogeneities are observed in the PSMs employing fluorescence microscopy. A quantitative analysis of the heterogeneity as well as the dynamics of the lipid domains is described.

Multifunctional Porous Bilayer Artificial Skin for Enhanced Wound Healing.

Meeting the exacting demands of wound healing encompasses rapid coagulation, superior exudate absorption, high antibacterial efficacy, and imperative support for cell growth. In this study, by emulating the intricate structure of natural skin, we prepare a multifunctional porous bilayer artificial skin to address these critical requirements. The bottom layer, mimicking the dermis, is crafted through freeze-drying a gel network comprising carboxymethyl chitosan (CMCs) and gelatin (GL), while the top layer, emulating the epidermis, is prepared via electrospinning poly(l-lactic acid) (PLLA) nanofibers. With protocatechuic aldehyde and gallium ion complexation (PA@Ga) as cross-linking agents, the bottom PA@Ga-CMCs/GL layer featured an adjustable pore size (78-138 µm), high hemostatic performance (67s), and excellent bacterial inhibition rate (99.9%), complemented by an impressive liquid-absorbing capacity (2000% swelling rate). The top PLLA layer, with dense micronanostructure and hydrophobic properties, worked as a shield to effectively thwarted liquid or bacterial penetration. Furthermore, accelerated wound closure, reduced inflammatory responses, and enhanced formation of hair follicles and blood vessels are achieved by the porous artificial skin covered on the surface of wound. Bilayer artificial skin integrates the advantages of nanofibers and freeze-drying porous materials to effectively replicate the protective properties of the epidermal layer of the skin, as well as the cell migration and tissue regeneration of the dermis. This bioabsorbable artificial skin demonstrates structural and functional comparability to real skin, which would advance the field of wound care through its multifaceted capabilities.

Efficient and rapid digestion of proteins with a dual-enzyme microreactor featuring 3-D pores formed by dopamine/polyethyleneimine/acrylamide-coated KIT-6 molecular sieve.

The microreactor with two types of immobilized enzymes, exhibiting excellent orthogonal performance, represents an effective approach to counteract the reduced digestion efficiency resulting from the absence of a single enzyme cleavage site, thereby impacting protein identification. In this study, we developed a hydrophilic dual-enzyme microreactor characterized by rapid mass transfer and superior enzymatic activity. Initially, we selected KIT-6 molecular sieve as the carrier for the dual-IMER due to its three-dimensional network pore structure. Modification involved co-deposition of polyethyleneimine (PEI) and acrylamide (AM) as amine donors, along with dopamine to enhance material hydrophilicity. Remaining amino and double bond functional groups facilitated stepwise immobilization of trypsin and Glu-C. Digestion times for bovine serum albumin (BSA) and bovine hemoglobin (BHb) on the dual-IMER were significantly reduced compared to solution-based digestion (1 min vs. 36 h), resulting in improved sequence coverage (91.30% vs. 82.7% for BSA; 90.24% vs. 89.20% for BHb). Additionally, the dual-IMER demonstrated excellent durability, retaining 96.08% relative activity after 29 reuse cycles. Enhanced protein digestion efficiency can be attributed to several factors: (1) KIT-6's large specific surface area, enabling higher enzyme loading capacity; (2) Its three-dimensional network pore structure, facilitating faster mass transfer and substance diffusion; (3) Orthogonality of trypsin and Glu-C enzyme cleavage sites; (4) The spatial effect introduced by the chain structure of PEI and glutaraldehyde's spacing arm, reducing spatial hindrance and enhancing enzyme-substrate interactions; (5) Mild and stable enzyme immobilization. The KIT-6-based dual-IMER offers a promising technical tool for protein digestion, while the PDA/PEI/AM-KIT-6 platform holds potential for immobilizing other proteins or active substances.

Optimized Electrophoretic Deposition of Chitosan/Mesoporous Glass Nanoparticles with Gentamicin on Titanium Implants: Enhancing Hemocompatibility and Antibacterial Activity.

Titanium-based implants have long been studied and used for applications in bone tissue engineering, thanks to their outstanding mechanical properties and appropriate biocompatibility. However, many implants struggle with osseointegration and attachment and can be vulnerable to the development of infections. In this work, we have developed a composite coating via electrophoretic deposition, which is both bioactive and antibacterial. Mesoporous bioactive glass particles with gentamicin were electrophoretically deposited onto a titanium substrate. In order to validate the hypothesis that the quantity of particles in the coatings is sufficiently high and uniform in each deposition process, an easy-to-use image processing algorithm was designed to minimize human dependence and ensure reproducible results. The addition of loaded mesoporous particles did not affect the good adhesion of the coating to the substrate although roughness was clearly enhanced. After 7 days of immersion, the composite coatings were almost dissolved and released, but phosphate-related compounds started to nucleate at the surface. With a simple and low-cost technique like electrophoretic deposition, and optimized stir and suspension times, we were able to synthesize a hemocompatible coating that significantly improves the antibacterial activity when compared to the bare substrate for both Gram-positive and Gram-negative bacteria.

Mesoporous Oxidized Mn-Ca Nanoparticles as Potential Antimicrobial Agents for Wound Healing.

Managing chronic non-healing wounds presents a significant clinical challenge due to their frequent bacterial infections. Mesoporous silica-based materials possess robust wound-healing capabilities attributed to their renowned antimicrobial properties. The current study details the advancement of mesoporous silicon-loaded MnO and CaO molecules (HMn-Ca) against bacterial infections and chronic non-healing wounds. HMn-Ca was synthesized by reducing manganese chloride and calcium chloride by urotropine solution with mesoporous silicon as the template, thereby transforming the manganese and calcium ions on the framework of mesoporous silicon. The developed HMn-Ca was investigated using scanning electron microscopy (SEM), transmission electron microscope (TEM), ultraviolet-visible (UV-visible), and visible spectrophotometry, followed by the determination of Zeta potential. The production of reactive oxygen species (ROS) was determined by using the 3,3,5,5-tetramethylbenzidine (TMB) oxidation reaction. The wound healing effectiveness of the synthesized HMn-Ca is evaluated in a bacterial-infected mouse model. The loading of MnO and CaO inside mesoporous silicon enhanced the generation of ROS and the capacity of bacterial capture, subsequently decomposing the bacterial membrane, leading to the puncturing of the bacterial membrane, followed by cellular demise. As a result, treatment with HMn-Ca could improve the healing of the bacterial-infected wound, illustrating a straightforward yet potent method for engineering nanozymes tailored for antibacterial therapy.

Anti-Inflammatory, Antidiabetic, and Antioxidant Properties of Extracts Prepared from Pinot Noir Grape Marc, Free and Incorporated in Porous Silica-Based Supports.

This study presents properties of hydroethanolic extracts prepared from Pinot Noir (PN) grape pomace through conventional, ultrasound-assisted or solvothermal extraction. The components of the extracts were identified by HPLC. The total content of polyphenols, flavonoids, anthocyanins, and condensed tannins, as well as antioxidant activity and α-glucosidase inhibitory activity of extracts were evaluated using UV-vis spectroscopy. All extracts were rich in phenolic compounds, proving a good radical scavenging activity. The extract obtained by conventional extraction at 80 °C showed the best α-glucosidase inhibitory activity close to that of (-)-epigallocatechin gallate. To improve the chemical stability of polyphenols, the chosen extract was incorporated in porous silica-based supports: amine functionalized silica (MCM-NH2), fucoidan-coated amine functionalized silica (MCM-NH2-Fuc), MCM-41, and diatomite. The PN extract exhibited moderate activity against Gram-positive S. aureus (MIC = 156.25 µg/mL) better than against Gram-negative E. coli (MIC = 312.5 µg/mL). The biocompatibility of PN extract, free and incorporated in MCM-NH2 and MCM-NH2-Fuc, was assessed on RAW 264.7 mouse macrophage cells, and the samples showcased a good cytocompatibility at 10 µg/mL concentration. At this concentration, PN and PN@MCM-NH2-Fuc reduced the inflammation by inhibiting NO production. The anti-inflammatory potential against COX and LOX enzymes of selected samples was evaluated and compared with that of Indomethacin and Zileuton, respectively. The best anti-inflammatory activity was observed when PN extract was loaded on MCM-NH2-Fuc support.

Designing Mesoporous Prussian Blue@zinc Phosphate Nanoparticles with Hierarchical Pores for Varisized Guest Delivery and Photothermally-Augmented Chemo-Starvation Therapy.

Background: With the rapid development of nanotechnology, constructing a multifunctional nanoplatform that can deliver various therapeutic agents in different departments and respond to endogenous/exogenous stimuli for multimodal synergistic cancer therapy remains a major challenge to address the inherent limitations of chemotherapy. Methods: Herein, we synthesized hollow mesoporous Prussian Blue@zinc phosphate nanoparticles to load glucose oxidase (GOx) and DOX (designed as HMPB-GOx@ZnP-DOX NPs) in the non-identical pore structures of their HMPB core and ZnP shell, respectively, for photothermally augmented chemo-starvation therapy. Results: The ZnP shell coated on the HMPB core, in addition to providing space to load DOX for chemotherapy, could also serve as a gatekeeper to protect GOx from premature leakage and inactivation before reaching the tumor site because of its degradation characteristics under mild acidic conditions. Moreover, the loaded GOx can initiate starvation therapy by catalyzing glucose oxidation while causing an upgradation of acidity and H2O2 levels, which can also be used as forceful endogenous stimuli to trigger smart delivery systems for therapeutic applications. The decrease in pH can improve the pH-sensitivity of drug release, and O2 can be supplied by decomposing H2O2 through the catalase-like activity of HMPBs, which is beneficial for relieving the adverse conditions of anti-tumor activity. In addition, the inner HMPB also acts as a photothermal agent for photothermal therapy and the generated hyperthermia upon laser irradiation can serve as an external stimulus to further promote drug release and enzymatic activities of GOx, thereby enabling a synergetic photothermally enhanced chemo-starvation therapy effect. Importantly, these results indicate that HMPB-GOx@ZnP-DOX NPs can effectively inhibit tumor growth by 80.31% and exhibit no obvious systemic toxicity in mice. Conclusion: HMPB-GOx@ZnP-DOX NPs can be employed as potential theranostic agents that incorporate multiple therapeutic modes to efficiently inhibit tumors.

Ultrasonic Preparation of Nano-CaCO3 Templates and Hollow Mesoporous SiO2 Nanoparticles for Voriconazole Loading.

CaCO3 nanoparticles (nano-CaCO3) as nano-templates were prepared using CaCl2 and Na2CO3 solutions under controlled sonication (19.5 kHz). Using the same ultrasonic device, subsequently, hollow mesoporous silica nanoparticles (HMSNs) were obtained by the hard template of nano-CaCO3. HMSNs were selected as carriers for the antifungal drug voriconazole (VOR) loading to overcome poor water solubility. Three-dimensional CaCO3 nanosheets HMSNs were obtained under gentle sonication. Three-dimensional CaCO3 nanosheets of 24.5 nm (hydrodynamic diameter) were obtained under 17.6 W for 3 min. HMSNs were synthesized by double-template method with nano-CaCO3 as the hard template. Transmission electron microscopy measurements showed that the prepared HMSNs possess hollow structures with particle size between 110 and 120 nm. Nitrogen physisorption at -196 °C revealed that the HMSNs had high surface area (401.57 m2/g), high pore volume (0.11 cm3/g), and uniform pore size (2.22 nm) that facilitated the effective encapsulation of VOR in the HMSNs. The loading capacity of VOR (wt%) on the HMSNs was 7.96%, and the total VOR release amount of VOR-HMSNs material was 71.40% at 480 min. The kinetic model confirmed that the release mechanism of HMSNs nanoparticles followed Fickian diffusion at pH = 7.4 and 37 °C. Moreover, the cumulative VOR release at 42 °C (86.05%) was higher than that at 37 °C (71.40%). The cumulative release amount of VOR from the VOR-HMSNs material was 92.37% at pH = 5.8 at the same temperature. Both nano-CaCO3 templates and HMSNs were prepared by sonication at 19.5 kHz. The as-prepared HMSNs can effectively encapsulate VOR and released drug by Fickian diffusion.

Micro-CT determination of the porosity of two tricalcium silicate sealers applied using three obturation techniques.

PURPOSE: Using X-ray micro-computed tomography (micro-CT), the aim of this study was to measure the porosity of two tricalcium silicate sealers (EndoSequence BC and NeoSealer Flo) applied using three obturation techniques (single-cone, warm-vertical, and cold-lateral) to six single-rooted human teeth. METHODS: Six extracted, single-rooted human teeth were shaped with ProTaper Next rotary files and obturated with EndoSequence BC or NeoSealer Flo sealers and gutta-percha (GP) using one of the three techniques above. Micro-CT was used to map the full length of the canals. Deep learning cross-sectional segmentation was used to analyze image slices of the apical (0-2 mm) and coronal (14-16 mm from the apex) regions (n = 230-261 per tooth) for the areas of GP and sealer, as well as porosity. Median (%) with interquartile range of porosity were calculated , and the results were statistically analyzed with the Kruskal-Wallis test. RESULTS: In the apical region, EndoSequence BC had significantly fewer pores than NeoSealer Flo with the single-cone obturation (% median-interquartile range, IQR: 0.00-1.62) and warm-vertical condensation (5.57-10.32) techniques, whereas in the coronal region, NeoSealer Flo had significantly fewer pores than EndoSequence BC with these two techniques (0.39-5.02) and (0.10-0.19), respectively. There was no significant difference in porosity between the two sealers for the cold-lateral condensation technique in both the apical and coronal regions. CONCLUSION: For optimal obturation, the choice of technique and sealer is critical.

A novel 3D nitrogen-doped porous carbon supported Fe-Cu bimetallic nanoparticles composite derived from lignin: an efficient peroxymonosulfate activator for naphthalene degradation.

A novel 3D nitrogen-doped porous carbon supported Fe-Cu bimetallic nanoparticles composite (Fe-Cu-N-PC) was prepared via direct pyrolysis by employing black liquor lignin as a main precursor, and it was utilized as a novel catalyst for PMS activation in degrading naphthalene. Under the optimum experimental conditions, the naphthalene degradation rate was up to 93.2% within 60 min in the Fe-Cu-N-PC/PMS system. The porous carbon framework of Fe-Cu-N-PC could facilitate the quick molecule diffusion of reactants towards the inner bimetallic nanoparticles and enriched naphthalene molecules from the solution by a specific adsorption, which increased the odds of contact between naphthalene and reactive oxygen species and improved the reaction efficiency. The quenching reaction proved that the non-free radical pathway dominated by 1O2 was the main way in naphthalene degradation, while the free radical pathway involving SO4·- and ·OH only played a secondary role. Moreover, owing to its high magnetization performance, Fe-Cu-N-PC could be magnetically recovered and maintained excellent naphthalene degradation rate after four degradation cycles. This research will offer a theoretical basis for the construction of facile, efficient, and green technologies to remediate persistent organic pollutants in the environment.

Chaotic Transport of Solutes in Unsaturated Porous Media.

Unsaturated porous media, characterized by the combined presence of several immiscible fluid phases in the pore space, are highly relevant systems in nature, because they control the fate of contaminants and the availability of nutrients in the subsoil. However, a full understanding of the mechanisms controlling solute mixing in such systems is still missing. In particular, the role of saturation in the development of chaotic solute mixing has remained unexplored. Using three-dimensional numerical simulations of flow and transport at the pore scale, built upon X-ray tomograms of a porous medium at different degrees of liquid (wetting)-phase saturation, we show the occurrence of chaotic dynamics in both the deformation of the solute plume, as characterized by computed chaos metrics (Lyapunov exponents), and the mixing of the injected solute. Our results show an enhancement of these chaotic dynamics at lower saturation and their occurrence even under diffusion-relevant conditions over the medium's length, also being strengthened by larger flow velocities. These findings highlight the dominant role of the pore-scale spatial heterogeneity of the system, enhanced by the presence of an immiscible phase (e.g., air), on the mixing efficiency. This represents a stepping stone for the assessment of mixing and reactions in unsaturated porous media.