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.

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.

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.

Biosensors for Cancer Biomarkers Based on Mesoporous Silica Nanoparticles.

Mesoporous silica nanoparticles (MSNs) exhibit highly beneficial characteristics for devising efficient biosensors for different analytes. Their unique properties, such as capabilities for stable covalent binding to recognition groups (e.g., antibodies or aptamers) and sensing surfaces, open a plethora of opportunities for biosensor construction. In addition, their structured porosity offers capabilities for entrapping signaling molecules (dyes or electroactive species), which could be released efficiently in response to a desired analyte for effective optical or electrochemical detection. This work offers an overview of recent research studies (in the last five years) that contain MSNs in their optical and electrochemical sensing platforms for the detection of cancer biomarkers, classified by cancer type. In addition, this study provides an overview of cancer biomarkers, as well as electrochemical and optical detection methods in general.

Improving the hemocompatibility of a porohyperelastic layered vascular graft using luminal reversal microflows.

Vascular graft thrombosis is a long-standing clinical problem. A myriad of efforts have been devoted to reducing thrombus formation following bypass surgery. Researchers have primarily taken a chemical approach to engineer and modify surfaces, seeking to make them more suitable for blood contacting applications. Using mechanical forces and surface topology to prevent thrombus formation has recently gained more attention. In this study, we have designed a bilayered porous vascular graft capable of repelling platelets and destabilizing absorbed protein layers from the luminal surface. During systole, fluid penetrates through the graft wall and is subsequently ejected from the wall into the luminal space (Luminal Reversal Flow - LRF), pushing platelets away from the surface during diastole. In-vitro hemocompatibility tests were conducted to compare platelet deposition in high LRF grafts with low LRF grafts. Graft material properties were determined and utilized in a porohyperelastic (PHE) finite element model to computationally predict the LRF generation in each graft type. Hemocompatibility testing showed significantly lower platelet deposition values in high versus low LRF generating grafts (median±IQR = 5,708 ± 987 and 23,039 ± 3,310 platelets per mm2, respectively, p=0.032). SEM imaging of the luminal surface of both graft types confirmed the quantitative blood test results. The computational simulations of high and low LRF generating grafts resulted in LRF values of -10.06 µm/s and -2.87 µm/s, respectively. These analyses show that a 250% increase in LRF is associated with a 75.2% decrease in platelet deposition. PHE vascular grafts with high LRF have the potential to improve anti-thrombogenicity and reduce thrombus-related post-procedure complications. Additional research is required to overcome the limitations of current graft fabrication technologies that further enhance LRF generation.

Immunological assay using a solid-state pore with a low limit of detection.

Emerging infectious diseases, cancer, and other diseases are quickly tested mainly via immune reactions based on specific molecular recognition between antigens and antibodies. By changing the diameter of solid-state pores, biomolecules of various sizes can be rapidly detected at the single-molecule level. The combination of immunoreactions and solid-state pores paves the way for an efficient testing method with high specificity and sensitivity. The challenge in developing this method is achieving quantitative analysis using solid-state pores. Here, we demonstrate a method with a low limit of detection for testing tumor markers using a combination of immunoreactions and solid-state pore technology. Quantitative analysis of the mixing ratio of two and three beads with different diameters was achieved with an error rate of up to 4.7%. The hybrid solid-state pore and immunoreaction methods with prostate-specific antigen (PSA) and anti-PSA antibody-modified beads achieved a detection limit of 24.9 fM PSA in 30 min. The hybrid solid-state pore and immunoreaction enabled the rapid development of easy-to-use tests with lower limit of detection and greater throughput than commercially available immunoassay for point-of-care testing.

Evaluation of the Ocular Safety of Hollow Mesoporous Organosilica Nanoparticles with Different Tetrasulfur Bond Content.

Background: Drug therapy for eye diseases has been limited by multiple protective mechanisms of the eye, which can be improved using well-designed drug delivery systems. Mesoporous silica nanoparticles (MSNs) had been used in many studies as carriers of therapeutic agents for ocular diseases treatment. However, no studies have focused on ocular biosafety. Considering that MSNs containing tetrasulfur bonds have unique advantages and have drawn increasing attention in drug delivery systems, it is necessary to explore the ocular biosafety of tetrasulfur bonds before their widespread application as ophthalmic drug carriers. Methods: In this study, hollow mesoporous silica nanoparticles (HMSNs) with different tetrasulfur bond contents were prepared and characterized. The ocular biosafety of HMSN-E was evaluated in vitro on the three selected ocular cell lines, including corneal epithelial cells, lens epithelial cells and retinal endothelial cells (HREC), and in vivo by using topical eye drops and intravitreal injections. Results: In cellular experiments, HMSNs caused obvious S content-dependent cytotoxic effect. HMSNs with the highest tetrasulfur bond content (HMSN-E), showed the highest cytotoxicity among all the HMSNs, and HREC was the most vulnerable cell to HMSN-E. It was shown that HMSN-E could react with intracellular GSH to generate H2S and decrease intracellular GSH concentration. Treatment of HREC with HMSN-E increased intracellular ROS, decreased mitochondrial membrane potential, and induced cell cycle arrest at the G1/S checkpoint, finally caused apoptosis and necrosis of HREC. Topical eye drops of HMSN-E could cause corneal damage. The intravitreal injection of HMSN-E could induce inflammation in the vitreum and ganglion cell layers, resulting in vitreous opacities and retinal abnormalities. Conclusion: The incorporation of tetrasulfur bonds into HMSN can have toxic effects on ocular tissues. Therefore, when mesoporous silica nanocarriers are designed for ophthalmic pharmaceuticals, the ocular toxicity of the tetrasulfur bonds should be considered.

Biocompatibility, bioactivity, porosity, and sealer/dentin interface of bioceramic ready-to-use sealers using a dentin-tube model.

This study evaluated the biocompatibility, bioactivity, porosity, and sealer/dentin interface of Sealer Plus BC (SP), Bio-C Sealer (BIOC), TotalFill BC Sealer (TF), and AH Plus (AHP). Dentin tubes filled with the sealers and empty tubes (control group) were implanted in the subcutaneous tissue of rats for different periods (n = 6 per group/period). Number of inflammatory cells (ICs), capsule thickness, von Kossa reaction, interleukin-6 (IL-6) and osteocalcin (OCN) were evaluated. Porosity and voids in the interface dentin/sealers were assessed by micro-computed tomography. The data were submitted to ANOVA/Tukey's tests (α = 0.05). Greater capsule thickness, ICs and IL-6 immunolabeling cells were observed in AHP. No significant difference in thickness of capsule, ICs, and IL-6- immunolabeling cells was detected between SP and TF, in all periods, and after 30 and 60 days between all groups. At 60 days all groups had reduction in capsule thickness, ICs and IL-6 immunolabeling cells. Von Kossa-positive and birefringent structures were observed in the capsules around the sealers. BIOC, SP, and TF exhibited OCN-immunolabeling cells. All sealers had porosity values below 5%, besides low and similar interface voids. BIOC, SP and TF are biocompatible, bioactive, and have low porosity and voids. The dentin-tube model used is an alternative for evaluating bioceramic materials.

3D Porous Polymer Scaffold-Conjugated KGF-Mimetic Peptide Promotes Functional Skin Regeneration in Chronic Diabetic Wounds.

The re-epithelialization process gets severely dysregulated in chronic nonhealing diabetic foot ulcers/wounds. Keratinocyte growth factor (KGF or FGF-7) is the major modulator of the re-epithelialization process, which regulates the physiological phenotypes of cutaneous keratinocytes. The existing therapeutic strategies of growth factor administration have several limitations. To overcome these, we have designed a KGF-mimetic peptide (KGFp, 13mer) based on the receptor interaction sites in murine KGF. KGFp enhanced migration and transdifferentiation of mouse bone marrow-derived MSCs toward keratinocyte-like cells (KLCs). A significant increase in the expression of skin-specific markers Bnc1 (28.5-fold), Ck5 (14.6-fold), Ck14 (26.1-fold), Ck10 (187.7-fold), and epithelial markers EpCam (23.3-fold) and Cdh1 (64.2-fold) was associated with the activation of ERK1/2 and STAT3 molecular signaling in the KLCs. Further, to enhance the stability of KGFp in the wound microenvironment, it was conjugated to biocompatible 3D porous polymer scaffolds without compromising its active binding sites followed by chemical characterization using Fourier transform infrared spectroscopy, field-emission scanning electron microscopy, dynamic mechanical analysis, and thermogravimetry. In vitro evaluation of the KGFp-conjugated 3D polymer scaffolds revealed its potential for transdifferentiation of MSCs into KLCs. Transplantation of allogeneic MSCGFP using KGFp-conjugated 3D polymer scaffolds in chronic nonhealing type 2 diabetic wounds (db/db transgenic, 50-52 weeks old male mice) significantly enhanced re-epithelialization-mediated wound closure rate (79.3%) as compared to the control groups (Untransplanted -22.4%, MSCGFP-3D polymer scaffold -38.5%). Thus, KGFp-conjugated 3D porous polymer scaffolds drive the fate of the MSCs toward keratinocytes that may serve as potential stem cell delivery platform technology for tissue engineering and transplantation.

Additive manufacturing of bioactive and biodegradable poly (lactic acid)-tricalcium phosphate scaffolds modified with zinc oxide for guided bone tissue repair.

Bioactive and biodegradable scaffolds that mimic the natural extracellular matrix of bone serve as temporary structures to guide new bone tissue growth. In this study, 3D-printed scaffolds composed of poly (lactic acid) (PLA)-tricalcium phosphate (TCP) (90-10 wt.%) were modified with 1%, 5%, and 10 wt.% of ZnO to enhance bone tissue regeneration. A commercial chain extender named Joncryl was incorporated alongside ZnO to ensure the printability of the composites. Filaments were manufactured using a twin-screw extruder and subsequently used to print 3D scaffolds via fused filament fabrication (FFF). The scaffolds exhibited a homogeneous distribution of ZnO and TCP particles, a reproducible structure with 300 µm pores, and mechanical properties suitable for bone tissue engineering, with an elastic modulus around 100 MPa. The addition of ZnO resulted in enhanced surface roughness on the scaffolds, particularly for ZnO microparticles, achieving values up to 241 nm. This rougher topography was responsible for enhancing protein adsorption on the scaffolds, with an increase of up to 85% compared to the PLA-TCP matrix. Biological analyses demonstrated that the presence of ZnO promotes mesenchymal stem cell (MSC) proliferation and differentiation into osteoblasts. Alkaline phosphatase (ALP) activity, an important indicator of early osteogenic differentiation, increased up to 29%. The PLA-TCP composite containing 5% ZnO microparticles exhibited an optimized degradation rate and enhanced bioactivity, indicating its promising potential for bone repair applications.

Constructing molecularly imprinted membranes with instant noodles-like structure for selectively separating acteoside.

Acteoside (ACT) was the main bioactive components in phenylethanoid glycosides of Cistanche tubulosa. Currently, the development of an efficient method for selectively separating ACT was crucial. Consequently, yolk-shell magnetic mesoporous carbon (YSMMC) was synthesized as a nanofiller to prepare molecularly imprinted membranes (ACT-MIMs) with instant noodles-like structure for selectively separating ACT. The numerous YSMMC were moved to the upper surface of ACT-MIMs by magnetic guidance and constructed the instant noodles-like structure in ACT-MIMs. The instant noodle-like structure increased the surface roughness of ACT-MIMs, which was conducive to improving the effective imprinted interface, increasing the selectivity of ACT-MIMs. In addition, the instant noodle-like structure had dendritic interleaved pathways in ACT-MIMs. The dendritic interleaved pathways can intercept ACT through ACT-MIMs, enhancing the permselectivity of ACT-MIMs. The prepared YSMMC possessed the dendritic shell and interlayer cavity structure can provide a great accommodation space, improving the rebinding capacities of ACT-MIMs. The high permselectivity (14.49), remarkable selectivity (7.52), and excellent rebinding capacity (120.48 mg/g) were achieved for the prepared ACT-MIMs. Thus, the design of ACT-MIMs with the instant noodles-like structure were valuable for selectively separating of bioactive components.

Bimetallic porous Mn/Co oxide nanosheets with efficient oxidase-mimicking activity for the sensitive colorimetric determination of resveratrol in different matrices.

BACKGROUND: Resveratrol, a natural polyphenol compound used as an ingredient in dietary supplements, and pharmaceuticals, has gained significant attention due to its potential health benefits. However, the accurate and sensitive determination of resveratrol in complex matrices remains a challenge. In this study, we propose the utilization of bimetallic porous Mn/Co oxide nanosheets (MnCoO-NSs) as catalysts for the colorimetric determination of resveratrol. RESULTS: The bimetallic porous MnCoO-NSs were prepared through a facile one-stone-two-birds strategy. These nanosheets exhibited superior oxidase-mimicking activity, as evidenced by the catalytic oxidation of the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB), producing a blue-colored oxTMB species with a prominent absorbance peak at 655 nm. The catalytic activity was promoted through the production of superoxide anion (O2•-), which enhanced the affinity of MnCoO-NSs to the TMB molecules. Upon the addition of resveratrol, the oxidation process was inhibited, resulting in rapid fading of the blue color. This colorimetric sensing platform exhibited a linear response to resveratrol concentrations over the range of 2.2-87.6 µM, with a limit of detection of 0.210 µM. The method was further applied for the determination of resveratrol in different matrices including biological fluids, pharmaceuticals, and environmental water. SIGNIFICANCE: The utilization of these MnCoO-NSs offers a simple and cost-effective alternative to conventional analytical techniques for the determination of resveratrol. Their high sensitivity, selectivity, and stability enable accurate measurements of resveratrol in various complex matrices. This research has implications in areas such as pharmaceutical analysis, biomedical research, and environmental analysis, where the reliable determination of resveratrol is crucial for assessing its therapeutic potential and ensuring product quality.

Exploitation of porphyrin-based titanium-rich porous organic polymers for targeted phosphopeptide enrichment from the serum of colorectal cancer individuals.

A porphyrin-based titanium-rich porous organic polymer (Th-PPOPs@Ti4+) was designed based on immobilized metal ion affinity chromatography technique and successfully applied to phosphopeptide enrichment with 5,10,15,20-tetrakis(4-carboxyphenyl) porphine tetramethyl ester (TCPTE), 2,3-dihydroxyterephthalaldehyde (DHTA), and 2,3,4-trihydroxybenzaldehyde (THBA) as raw materials. Th-PPOPs@Ti4+ exhibited remarkable sensitivity (0.5 fmol), high selectivity (ß-casein: BSA = 1:2000, molar ratio), outstanding recovery (95.0 ± 1.9%), reusability (10 times), and superior loading capacity (143 mg·g-1). In addition, Th-PPOPs@Ti4+ exhibited excellent ability to specifically capture phosphopeptides from the serum of colorectal cancer (CRC) individuals and normal subjects. Sixty phosphopeptides assigned to 35 phosphoproteins were obtained from the serum of CRC individuals, and 43 phosphopeptides allocated to 28 phosphoproteins were extracted in the serum of healthy individuals via nano-LC-MS/MS. Gene ontology assays revealed that the detected phosphoproteins may be inextricably tied to CRC-associated events, including response to estrogen, inflammatory response, and heparin binding, suggesting that it is possible that these correlative pathways may be implicated in the pathogenesis of CRC.

The Modified Harrington Procedure for Metastatic Peri-Acetabular Bone Lesion Using a Novel Highly Porous Titanium Revision Shell with Long Lever Arm Screw.

Background and Objectives: Peri-acetabular metastases often lead to significant pain and functional impairment. Surgical interventions, including the Harrington procedure, aim to address these challenges. This study evaluates a modified Harrington procedure using the MUTARS® PRS® (Pelvic Revision Shell) with an 8 mm fixation screw for severe acetabular defects resulting from metastatic lesions. Materials and Methods: Retrospective analysis of 12 patients treated between January 2020 and December 2023 was conducted. The procedure involved using the novel MUTARS® PRS® with an 8 mm in diameter dome screw (length 70-100 mm). Outcome measures included implant positioning changes, complication rates, functional outcomes, implant longevity, and patient survival. Radiological assessments were performed postoperatively, with follow-ups at 3, 6, 12 months, and annually thereafter. Results: Average follow-up was 15 ± 11 months, with 67% patient survival at 1 year and 44% at 2 years. Implant survivorship remained 100%. Harris Hip Score improved significantly from 37 ± 22 preoperatively to 75 ± 15 at the last follow-up. No revisions involving implant components were reported. Complications occurred in 5 of 12 patients. Overall, PRS® demonstrates effective osseous ingrowth, high primary stability, immediate full weight-bearing, and low complication rates. Conclusions: PRS® integrates facilitating osseous ingrowth for preferable long-term outcomes, while efficiently transmitting the weight-bearing load to the intact aspect of the pelvis using a long 8 mm lever screw, enhancing the primary stability of the construct. It proves to be an effective and reproducible technique for managing destructive metastatic lesions of the acetabulum and peri-acetabular region, even in irradiated bone.

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.

Dosimetric impact of stopping power for human bone porosity with dual-energy computed tomography in scanned carbon-ion therapy treatment planning.

Few reports have documented how the accuracy of stopping power ratio (SPR) prediction for porous bone tissue affects the dose distribution of scanned carbon-ion beam therapy. The estimated SPR based on single-energy computed tomography (SECT) and dual-energy CT (DECT) were compared for the femur of a Rando phantom which simulates the porosity of human bone, NEOBONE which is the hydroxyapatite synthetic bone substitute, and soft tissue samples. Dose differences between SECT and DECT were evaluated for a scanned carbon-ion therapy treatment plan for the Rando phantom. The difference in the water equivalent length was measured to extract the SPR of the examined samples. The differences for SPR estimated from the DECT-SPR conversion were small with - 1.8% and - 3.3% for the Rando phantom femur and NEOBONE, respectively, whereas the differences for SECT-SPR were between 7.6 and 70.7%, illustrating a 1.5-mm shift of the range and a dose difference of 13.3% at maximum point in the evaluation of the dose distribution. This study demonstrated that the DECT-SPR conversion method better estimated the SPR of the porosity of bone tissues than SECT-SPR followed by the accurate range of the carbon-ion beams on carbon-ion dose calculations.

Mesoporous Graphene Oxide Nanocomposite Effective for Combined Chemo/Photo Therapy Against Non-Small Cell Lung Cancer.

Introduction: Lung cancer is the most common cancer worldwide, among which non-small cell lung cancer (NSCLC) accounts for about 80% of all lung cancers. Chemotherapy, a mainstay modality for NSCLC, has demonstrated restricted effectiveness due to the emergence of chemo-resistance and systemic side effects. Studies have indicated that combining chemotherapy with phototherapy, such as photodynamic therapy (PDT) and photothermal therapy (PTT), can enhance efficacy of therapy. In this work, an aminated mesoporous graphene oxide (rPGO)-protoporphyrin IX (PPIX)-hyaluronic acid (HA)@Osimertinib (AZD) nanodrug delivery system (rPPH@AZD) was successfully developed for combined chemotherapy/phototherapy for NSCLC. Methods: A pH/hyaluronidase-responsive nanodrug delivery system (rPPH@AZD) was prepared using mesoporous graphene oxide. Its morphology, elemental composition, surface functional groups, optical properties, in vitro drug release ability, photothermal properties, reactive oxygen species production, cellular uptake and cell viability were evaluated. In addition, the in vivo therapeutic effect, biocompatibility, and imaging capabilities of rPPH@AZD were verified by a tumor-bearing mouse model. Results: Aminated mesoporous graphene oxide (rPGO) plays a role as a drug delivery vehicle owing to its large specific surface area and ease of surface functionalization. rPGO exhibits excellent photothermal conversion properties under laser irradiation, while PPIX acts as a photosensitizer to generate singlet oxygen. AZD acts as a small molecule targeted drug in chemotherapy. In essence, rPPH@AZD shows excellent photothermal and fluorescence imaging effects in tumor-bearing mice. More importantly, in vitro and in vivo results indicate that rPPH@AZD can achieve hyaluronidase/pH dual response as well as combined chemotherapy/PTT/PDT anti-NSCLC treatment. Conclusion: The newly prepared rPPH@AZD can serve as a promising pH/hyaluronidase-responsive nanodrug delivery system that integrates photothermal/fluorescence imaging and chemo/photo combined therapy for efficient therapy against NSCLC.

3D-printed titanium porous prosthesis combined with the Masquelet technique for the management of large femoral bone defect caused by osteomyelitis.

BACKGROUND: The treatment of infected bone defects remains a clinical challenge. With the development of three-dimensional printing technology, three-dimensional printed implants have been used for defect reconstruction. The aim of this study was to investigate the clinical outcomes of three-dimensional printed porous prosthesis in the treatment of femoral defects caused by osteomyelitis. METHODS: Eleven patients with femoral bone defects following osteomyelitis who were treated with 3D-printed porous prosthesis at our institution between May 2017 and July 2021, were included. Eight patients were diagnosed with critical-sized defects, and the other three patients were diagnosed with shape-structural defects. A two-stage procedure was performed for all patients, and the infection was eradicated and bone defects were occupied by polymethylmethacrylate spacer during the first stage. The 3D-printed prosthesis was designed and used for the reconstruction of femoral defects in the second stage. Position of the reconstructed prostheses and bone growth were measured using radiography. The union rate, complications, and functional outcomes at the final follow-up were assessed. RESULTS: The mean length of the bone defect was 14.0 cm, union was achieved in 10 (91%) patients. All patients showed good functional performance at the most recent follow-up. In the critical-sized defect group, one patient developed a deep infection that required additional procedures. Two patients had prosthetic dislocations. Radiography demonstrated good osseous integration of the implant-bone interface in 10 patients. CONCLUSION: The 3D printed prostheses enable rapid anatomical and mechanically stable reconstruction of extreme femur bone defects, effectively shortens treatment time, and achieves satisfactory clinical outcomes.

Drug-Loaded Mesoporous Silica Nanoparticles Enhance Antitumor Immunotherapy by Regulating MDSCs.

Myeloid-derived suppressor cells (MDSCs) are recognized as major immune suppressor cells in the tumor microenvironment that may inhibit immune checkpoint blockade (ICB) therapy. Here, we developed a Stattic-loaded mesoporous silica nanoparticle (PEG-MSN-Stattic) delivery system to tumor sites to reduce the number of MDSCs in tumors. This approach is able to significantly deplete intratumoral MSDCs and thereby increase the infiltration of T lymphocytes in tumors to enhance ICB therapy. Our approach may provide a drug delivery strategy for regulating the tumor microenvironment and enhancing cancer immunotherapy efficacy.

Clinical Outcomes of Use of the Porous Glass Membrane Pumping Emulsification Device During Transarterial Chemoembolization for Hepatocellular Carcinoma.

BACKGROUND/AIM: The porous glass membrane pumping emulsification device enhances local therapeutic effects of transarterial chemoembolization for hepatocellular carcinoma (HCC); however, limited clinical outcomes have been reported. This study aimed to investigate the efficacy and safety of transarterial chemoembolization using the glass membrane pumping emulsification device for HCC. PATIENTS AND METHODS: Between 2019 and 2023, 58 patients (median age=73 years) with unresectable HCC underwent 73 transarterial chemoembolizations using the glass membrane pumping emulsification device at the Nagoya University Hospital. Treatment effects were assessed using contrast-enhanced computed tomography 1-3 months after therapy and every 2-3 months thereafter. RESULTS: The median size of treated tumors was 25.5 mm (45 solitary nodules). The median dosage of ethiodized oil mixed with the epirubicin solution was 3 ml. Complete and partial response were observed in 73% and 11% of patients, respectively. Local control rates at 6 and 12 months were 82.8% and 59.8%, respectively. The median time to recurrence after treatment was 581 days. No major treatment-related complications occurred. The number of tumors and therapeutic effects of the initial transarterial chemoembolization were significantly associated with better local control. CONCLUSION: The glass membrane pumping emulsification device facilitated the accumulation of more concentrated ethiodized oil within the tumor and effective local control.