High-Strength Injectable Hydrogel into Perivascular Interstitial Space Enhances Arterial Adventitial Stress.

Injectable hydrogels with strong mechanical properties have significant potential for biomedical applications, including the development of electronic skin, intelligent medical robots, as well as tissue engineering. In this study, we report on an injectable hydrogel with notable tensile strength and adhesion properties, achieved through cross-linking thiol-terminated four-arm poly (ethylene glycol) using silver-doped nano-hydroxyapatite, modified with dopamine. Subsequently, the hydrogel was injected in vivo through the perivascular interstitial space of rats. The hydrogel wrapped around the damaged abdominal aortic adventitia, which greatly increases the stress strength of the arterial adventitia. We found that the hydrogel was characterized by excellent biocompatibility, and it induced little immune response over a span of 21 days post-implantation. This simple and minimally invasive vascular protection strategy appears promising for the treatment of vascular diseases, such as abdominal aortic aneurysm (AAA).

A Dielectric Elastomer-Based Multimodal Capacitive Sensor.

Dielectric elastomer (DE) sensors have been widely used in a wide variety of applications, such as in robotic hands, wearable sensors, rehabilitation devices, etc. A unique dielectric elastomer-based multimodal capacitive sensor has been developed to quantify the pressure and the location of any touch simultaneously. This multimodal sensor is a soft, flexible, and stretchable dielectric elastomer (DE) capacitive pressure mat that is composed of a multi-layer soft and stretchy DE sensor. The top layer measures the applied pressure, while the underlying sensor array enables location identification. The sensor is placed on a passive elastomeric substrate in order to increase deformation and optimize the sensor's sensitivity. This DE multimodal capacitive sensor, with pressure and localization capability, paves the way for further development with potential applications in bio-mechatronics technology and other humanoid devices. The sensor design could be useful for robotic and other applications, such as fruit picking or as a bio-instrument for the diabetic insole.

Food emulsifier polysorbate 80 promotes the intestinal absorption of mono-2-ethylhexyl phthalate by disturbing intestinal barrier.

Di-2-ethylhexyl phosphate (DEHP) and its main toxic metabolite mono-2-ethylhexyl phthalate (MEHP) are the typical endocrine disrupting chemicals (EDCs) and widely affect human health. Our previous research reported that synthetic nonionic dietary emulsifier polysorbate 80 (P80, E433) had the promotional effect on the oral absorption of DEHP in rats. The aim of this study was to explore its mechanism of promoting oral absorption, focusing on the mucus barrier and mucosal barrier of the small intestine. A small molecule fluorescent probe 5-aminofluorescein-MEHP (MEHP-AF) was used as a tracker of MEHP in vivo and in vitro. First of all, we verified that P80 promoted the bioavailability of MEHP-AF in the long-term and low-dose exposure of MEHP-AF with P80 as a result of increasing the intestinal absorption of MEHP-AF. Afterwards, experimental results from Western blot, qPCR, immunohistochemistry, and immunofluorescence showed that P80 decreased the expression of proteins (mucus protein mucin-2, tight junction proteins claudin-1 and occludin) related to mucus barrier and mucosal barrier in the intestine, changed the integrity of intestinal epithelial cell, and increased the permeability of intestinal epithelial mucosa. These results indicated that P80 promoted the oral absorption of MEHP-AF by altering the intestinal mucus barrier and mucosal barrier. These findings are of great importance for assessing the safety risks of some food emulsifiers and clarifying the absorption mechanism of chemical pollutants in food, especially for EDCs.

Improved therapeutic index of the liposomal docetaxel-glutathione prepared by active click loading.

The clinical usage of docetaxel (DTX) is severely hindered by the dose-limiting neutropenia and peripheral neurotoxicity of polysorbate 80-solubilized DTX injection, and there are no alternative formulations until now. In this study, we developed a new liposomal formulation of DTX to reduce its toxicities, accompanying with the greatly improved antitumor activity. The DTX was encapsulated into liposomes in the form of hydrophilic glutathione (GSH)-conjugated prodrugs using a click drug loading method, which achieved a high encapsulation efficiency (∼95 %) and loading capacity (∼30 % wt). The resulting liposomal DTX-GSH provided a sustained and efficient DTX release (∼50 % within 48 h) in plasma, resulting in a greatly improved antitumor activities as compared with that of polysorbate 80-solubilized DTX injection in the subcutaneous and orthotopic 4T1 breast tumor bearing mice. Even large tumors > 500 mm3 could be effectively inhibited and shrunk after the administration of liposomal DTX-GSH. More importantly, the liposomal DTX-GSH significantly decreased the neutropenia and peripheral neurotoxicity as compared with that of polysorbate 80-solubilized DTX injection at the equivalent dose. These data suggested that the liposomal DTX-GSH might become a superior alternative formulation to the commercial DTX injection.

Preparation of carbon nanotubes by catalytic pyrolysis of dechlorinated PVC.

Plastic waste is attracting growing interest for its utilization potential as a valuable resource. However, conventional thermochemical methods can hardly achieve high-value utilization of certain plastics, such as polyvinyl chloride (PVC) characterized with high chlorine content. Here, a low-temperature aerobic pretreatment method was introduced to realize high-efficiency dechlorination of PVC, and then the dechlorinated PVC was used to prepare carbon nanotubes (CNTs) by a catalytic pyrolysis. The results demonstrate that oxygen can significantly promote the HCl release in a pretty low-temperature range (260-340 °C). Chlorine was almost completely eliminated at 280 °C under 20 % oxygen concentration. Compared to untreated PVC, using the dechlorinated PVC as raw material, higher carbon deposition was obtained and over 60 % CNTs could be collected from the carbon deposition. This study provides a high-value utilization way for the production of CNTs from waste PVC.

Interstitial Injection of Hydrogels with High-Mechanical Conductivity Relieves Muscle Atrophy Induced by Nerve Injury.

Injectable hydrogels have been extensively used in tissue engineering where high mechanical properties are key for their functionality at sites of high physiological stress. In this study, an injectable, conductive hydrogel is developed exhibiting remarkable mechanical strength that can withstand a pressure of 500 kPa (85% deformation rate) and display good fatigue resistance, electrical conductivity, and tissue adhesion. A stable covalent cross-linked network with a slip-ring structure by threading amino ß-cyclodextrin is formed onto the chain of a four-armed (polyethylene glycol) amino group, and then reacted with the four-armed (polyethylene glycol) maleimide under physiological conditions. The addition of silver nanowires enhances the hydrogel's electrical conductivity, enabling it to act as a good conductor in vivo. The hydrogel is injected into the fascial space, and the results show that the weight and muscle tone of the atrophied gastrocnemius muscle improve, subsequently alleviating muscle atrophy. Overall, this study provides a simple method for the preparation of a conductive hydrogel with high mechanical properties. In addition, the interstitial injection provides a strategy for the use of hydrogels in vivo.

Therapeutic Efficacy of Third-Generation Percutaneous Vertebral Augmentation System (PVAS) in Osteoporotic Vertebral Compression Fractures (OVCFs): A Systematic Review and Meta-analysis.

Purpose: This study aimed to assess whether the third-generation PVAS was superior to percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP) in treating patients with OVCFs. Methods: Databases, including Pubmed, Embase, and Cochrane library, were searched to identify relevant interventional and observational articles in vivo or in vitro comparing the third-generation PVAS to PVP/PKP in OVCFs patients. A meta-analysis was performed under the guidelines of the Cochrane Reviewer's Handbook. Results: 11 in vivo articles involving 1035 patients with 1320 segments of diseased vertebral bodies and 8 in vitro studies enrolling 40 specimens with 202 vertebral bodies were identified. The vivo studies indicated no significant differences were found in visual analog scale (VAS), Oswestry Disability Index (ODI), operation time, or injected cement volume (P > 0.05). The third-generation PVAS was associated with significant improvement in vertebral height and Cobb angle (P < 0.05) and also with a significantly lower risk of cement leakages and new fractures (P < 0.05). The vitro studies suggest that the third-generation PVAS was associated with better anterior vertebral height (AVH) and kyphotic angle (KA) after deflation and cement. No significant differences were found in stiffness or failure load after cement between the two groups (P > 0.05). Conclusion: Based on current evidence, although providing similar improvement in VAS and ODI, the third-generation PVAS may be superior to PVP/PKP in local kyphosis correction, vertebral height maintenance, and adverse events reduction. Further high-quality randomized studies are required to confirm these results.

Microplastic particles alter wheat rhizosphere soil microbial community composition and function.

The wide existence of microplastics (MPs) in the terrestrial systems is proved by -many studies, and their presence could potentially change the soil chem-physical properties and processes. Various types of microplastics may have different behaviors, inducing distinct effects on the soil ecosystems. However, the knowledge of microplastic impacts on rhizosphere soil bacterial community structure is limited. In our study, three types of microplastics, i.e., polyethylene (PE), polyvinylchloride (PVC) and polystyrene (PS), with the same particle size (200 µm) and concentration (2%) were used to investigate their influences on the rhizosphere soil bacterial communities. Results revealed that the alpha diversities (richness, evenness and diversity) of microbiota in the rhizosphere soil were variously decreased by the microplastics, especially the PE MPs. The relative abundance of some various phyla and genera related to pollution degradation was miscellaneously increased, indicating that the MPs with different characterizations may have miscellaneous biodegradation pathways. Moreover, the PICRUSt2 analysis demonstrated that PS decreased most functional category levels and led to a decrease of bacterial genus number, however, PE and PVC improved metabolic pathways and xenobiotics biodegradation and metabolism. Our findings offer important knowledge of how the microplastics with different characterizations influence rhizosphere soil bacterial communities and their related function.

Analysis of two minimally invasive procedures for osteoporotic vertebral compression fractures with intravertebral cleft: a systematic review and meta-analysis.

BACKGROUND: A systematic review and meta-analysis to assess the pros and cons of percutaneous vertebroplasty (PVP) versus kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCFs) with intravertebral cleft (IVC) including all available evidence from controlled trials. METHODS: Databases including Pubmed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched to identify relevant studies comparing PVP and PKP for OVCFs with IVC. The outcomes mainly included visual analog scale (VAS), Oswestry Disability Index (ODI), local kyphotic angle (LKA), rate of vertebral height (VH%), and adverse events. RESULTS: Nine studies enrolling 688 patients were eligible for meta-analysis. The results indicated no significant differences between the two groups in the short-and long-term VAS, ODI, LKA, or VH% (P > 0.05). Compared with PVP, PKP was associated with significantly longer operation time (P < 0.05), higher cost (P > 0.05), and more injected cement volume (P < 0.05). In terms of adverse events, PKP has a lower risk of cement leakage (P < 0.05), while with no significant difference in adjacent-level fracture rates (P > 0.05). CONCLUSION: The two procedures have similar short- and long-term pain relief, functional recovery, local kyphosis correction, and vertebral height maintenance in OVCFs with IVC. PKP is superior to PVP for the injected cement volume, and lower cement leakage rate, however, with longer operation time, more fluoroscopy times, and higher cost. Further randomized controlled trials (RCTs) should be conducted to confirm these results.

Application of Titanium Alloy 3D-Printed Artificial Vertebral Body for Stage III Kümmell's Disease Complicated by Neurological Deficits.

PURPOSE: The current study aimed to compare the clinical and radiographic results of the 3D-printed artificial vertebral body (3DP-AVB) and titanium mesh cage (TMC) for the treatment of Kümmell's disease (KD) complicated by neurological deficits. PATIENTS AND METHODS: From January 2014 to July 2018, 28 consecutive patients diagnosed with KD and nerve injuries in our department were treated by posterior vertebral column resection and internal fixation. The patients were divided into two groups (3DP-AVB group and TMC group) based on the different anterior column reconstruction implants. Clinical and radiographic parameters were used to evaluate the outcomes. RESULTS: The two groups achieved excellent clinical and radiographic results 1 month after surgery with no significant difference (P>0.05), while 3DP-AVB group showed better outcomes compared with TMC group during the follow-up after 6 months (P<0.05). The risk of subsidence in 3DP-AVB group was lower than that in TMC group (41.6% vs 87.5%, P<0.05), and severe subsidence (≥5 mm) was correlated with the recurrence of back pain and bad daily life function. No significant difference was found in the improvement of neurological function between the two groups (P>0.05). The blood loss and operation time in 3DP-AVB group were significantly less than both in TMC group (P<0.05). CONCLUSION: The lower incidence of cage subsidence, with a better long-term efficacy in maintaining the height of the fused segment, relieving back pain, and improving daily life function indicates that the 3DP-AVB may be a superior alternative for KD with neurological deficits.

Temperature/near-infrared light-responsive conductive hydrogels for controlled drug release and real-time monitoring.

Stimuli-responsive hydrogels with adaptable physical properties show great potential in the biomedical field. In particular, the collection of electrical signals is essential for precision medicine. Here, a simple strategy is demonstrated for achieving controlled drug release and real-time monitoring using an interpenetrating binary network consisting of a graphene aerogel and a poly(N-isopropylacrylamide) hydrogel with incorporated polydopamine nanoparticles (PDA-NPs). Owing to the good physical properties of graphene and the embedded PDA-NPs, the hybrid hydrogel shows enhanced mechanical properties and good electrical conductivity. In addition, the hybrid hydrogel also shows dual thermo- and near-infrared light responsiveness, as revealed by the controlled release of a model drug. In addition, as the hydrogel exhibits detectable changes in resistance during drug release, the drug-release behavior of the hydrogel can be monitored in real time using electrical signals. Moreover, owing to the abundance of catechol groups on the PDA-NPs, the hybrid hydrogel shows good tissue adhesiveness, as demonstrated using in vivo experiments. Thus, the developed hybrid hydrogel exhibits considerable practical applicability for drug delivery and precision medicine.

Binary blended co-delivery nanoparticles with the characteristics of precise pH-responsive acting on tumor microenvironment.

Although combined chemotherapy had achieved the ideal efficacy in clinical anti-cancer therapeutic, the issues that need to be addressed are non-targeting and toxic-side effects of small molecule chemical drug (SMCD). In this study, we designed and prepared a novel binary blended co-delivered nanoparticles (BBCD NPs) with pH-responsive feature on tumor microenvironment. The BBCD NPs consists of two kind of drug-loaded NPs, in one of which carboxymethyl chitosan (CMC) and Poly (lactic-co-glycolic acid) (PLGA) were chosen as delivery carrier to load anti-cancer drug vincristine (VCR), named CMC-PLGA-VCR NPs (or CPNPVCR); and in the other of which methoxy poly(ethylene glycol)-poly(ß-amino ester) (mPEG-PAE) were chosen as delivery carrier to load anti-fibrotic drug pirfenidone (PFD), named mPEG-PAE-PFD NPs (or PPNPPFD). Then, the two types of NPs (CPNPVCR and PPNPPFD) were physically mixed in mass ratios to form BBCD NPs, which was named CPNPVCR&PPNPPFD. CPNPVCR&PPNPPFD had good encapsulation efficiency and loading capacity, and the particle size distribution was uniform. In cytotoxicity experiments and non-contact co-culture studies in vitro, the model drugs loaded in CPNPVCR&PPNPPFD could respectively target cancer cell and cancer associated fibroblast (CAF) owing to the precise pH-sensitive drug release in the pharmacological targets and show stronger synergism than that of the combined treatment of two free drugs. As a modularity and assemble ability feature in design, BBCD NPs would have the advantages on the terms of concise on preparation process, controllable on quality standard, stable in natural environment storage. The research results can provide scientific evidence for the further development of a novel drug co-delivery system with multi-type cell targets.

Hierarchical Hydrogel Composite Interfaces with Robust Mechanical Properties for Biomedical Applications.

Cells sense and respond to a wide range of external signals, including chemical signals, topography, and interface mechanics, via interactions with the extracellular matrix (ECM), triggering the regulation of behavior and function. The ECM can be considered a hierarchical multiphase porous matrix with various components. Highly porous hydrogel-based biomaterials can mimic the critical ECM properties, to provide mechanical support for tissues and to regulate cellular behaviors, such as adhesion, proliferation, and differentiation. Herein, based on micro/nanoscale-topography-coupled mechanical action, recent advances in the fabrication and application of hydrogel composites with tunable mechanical properties and topography in biomedicine are summarized. In particular, recent findings showing that hydrogels with specifically designed structures not only influence a range of cellular processes and fit the needs of engineered tissues but also have pharmacological effects are emphasized.

One-step fabrication of functionalized poly(etheretherketone) surfaces with enhanced biocompatibility and osteogenic activity.

Polyetheretherketone (PEEK) has an elastic modulus similar to that of the bone; however, its use as a material for bone repair is limited by bio-inert surface chemistry and poor osteogenesis-inducing capacity. To address this issue, the PEEK surface was activated by ultraviolet radiation-induced grafting of methacrylated hyaluronic acid (MeHA) and titanium dioxide (TiO2) nanofibers via a one-step process. The modified PEEK surface was characterized by X-ray photoelectron and Fourier-transform infrared spectroscopy, and the extent of surface modification was evaluated by measuring static contact angles. Atomic force microscopy revealed that the PEEK surface grafted with electrospun TiO2 had abundant nanofibers and a roughness that was comparable to that of human cortical bone. In vitro experiment, rat bone mesenchymal stem cells showed increased adhesion, proliferation, and osteogenic differentiation capacity on TiO2-modified as compared to unmodified PEEK. Thus, PEEK that is surface-modified with electrospun TiO2 and MeHA has enhanced biocompatibility and can be an effective material for use in orthopedic implants and medical devices.

Dual-responsive colloidal microcapsules based on host-guest interaction on solid templates.

Colloidal microcapsules (MCs) have received considerable attention in the fields of microencapsulation, drug delivery as well as microreactors due to their unique nanoparticles-composed structure. In this study, dual-responsive colloidal MCs based on host-guest interaction were successfully fabricated via a layer-by-layer assembly method on sacrificial solid templates. Ferrocene-modified polyethylenimine (PEI-Fc) and cyclodextrin-modified polystyrene nanoparticles (PS-CD NPs) were used as building blocks for assembly. The colloidal MCs could be disassembled into nano-components upon addition of competitive adamantane (Ad) molecules or in the solution with a pH lower than 4.