Polypropylene mesh coated with hyaluronic acid/polyvinyl alcohol composite hydrogel for preventing bowel adhesion.

Polypropylene (PP) mesh is the most widely used prosthetic material in hernia repair. However, the efficacy of implanted PP mesh is often compromised by adhesion between viscera and PP mesh. Thus, there is a recognized need for developing an anti-adhesive PP mesh. Here, a composite hydrogel coated PP mesh with the prevention of adhesion after hernia repair was designed. The composite hydrogel coating was prepared from polyvinyl alcohol (PVA) and hyaluronic acid (HA) by using the freezing-thawing (FT) method. To overcome the shortcoming of the long time of the traditional freezing-thawing method, a small molecule 3,4-dihydroxyphenylacetic acid (DHPA) was introduced to promote the formation of composite hydrogel. The as-prepared composite hydrogel coating displayed modulus more closely resembling that of native abdominal wall tissue. In vitro studies illustrated that the resulting meshes showed excellent coating stability, hemocompatibility, and non-cytotoxicity. In vivo experiments using a rat abdominal wall defect model demonstrated that the composite hydrogel coated PP mesh could prevent the formation of adhesion, alleviate the inflammatory response, and reduce the deposition of collagen around the damaged tissue. These disclosed results manifested that the PP mesh coated with HA/PVA composite hydrogel might be a promising application in preventing adhesion for hernia repair.

Transformable Magnetic Liquid-Metal Nanoplatform for Intracellular Drug Delivery and MR Imaging-Guided Microwave Thermochemotherapy.

Improved techniques for the administration of chemotherapeutic drugs are required to enhance tumor therapy efficacy and reduce the side effects of chemotherapy due to insufficient targeting and limited intratumoral drug release. Controlled drug delivery systems combined with thermotherapy are expected to play an important role in personalized tumor therapy. Herein, a novel microwave-responsive transformable magnetic liquid-metal (MLM) nanoplatform is designed for effective endosomal escape that facilitates intracellular drug delivery and enhanced anticancer therapy. The MLM nanoplatform exhibits a sensitive magnetic resonance imaging function for imaging-guided therapy and brilliant synergistic effects of chemotherapy with microwave thermal therapy to kill tumor cells. Once endocytosed by targeted tumor cells, the deep penetration of microwave energy can be absorbed by the MLM nanoplatform to convert heat and reactive oxygen species, which induces the shape transformation from nanospheres to large rods, resulting in the physical disruption of the endosomal membrane for intracellular drug release. Furthermore, the MLM nanoplatform synergistic therapy could activate immunomodulatory effects by M1 macrophage polarization and T cell infiltration, thus inhibiting tumor growth and lung metastasis. This work based on microwave-driven transformable magnetic liquid-metal nanoplatform provides novel ways to precisely control drug delivery and high-efficiency cancer therapy.

A Visible Light Cross-Linked Underwater Hydrogel Adhesive with Biodegradation and Hemostatic Ability.

Hydrogel adhesives with integrated functionalities are still required to match their ever-expanding practical applications in the field of tissue repair and regeneration. A simple and effective safety strategy is reported, involving an in situ injectable polymer precursor and visible light-induced cross-linking. This strategy enables the preparation of a hydrogel adhesive in a physiological environment, offering wet adhesion to tissue surfaces, molecular flexibility, biodegradability, biocompatibility, efficient hemostatic performance, and the ability to facilitate liver injury repair. The proposed one-step preparation process of this polymer precursor involves the mixing of gelatin methacryloyl (GelMA), poly(thioctic acid) [P(TA)], poly(acrylic acid)/amorphous calcium phosphate (PAAc/ACP, PA) and FDA-approved photoinitiator solution, and a subsequent visible light irradiation after in situ injection into target tissues that resulted in a chemically-physically cross-linked hybrid hydrogel adhesive. Such a combined strategy shows promise for medical scenarios, such as uncontrollable post-traumatic bleeding.

Assembly of Metal-Phenolic Networks onto Microbubbles for One-Step Generation of Functional Microcapsules.

The one-step assembly of metal-phenolic networks (MPNs) onto particle templates can enable the facile, rapid, and robust construction of hollow microcapsules. However, the required template removal step may affect the refilling of functional species in the hollow interior space or the in situ encapsulation of guest molecules during the formation of the shells. Herein, a simple strategy for the one-step generation of functional MPNs microcapsules is proposed. This method uses bovine serum albumin microbubbles (BSA MBs) as soft templates and carriers, enabling the efficient pre-encapsulation of guest species by leveraging the coordination assembly of tannic acid (TA) and FeIII ions. The addition of TA and FeIII induces a change in the protein conformation of BSA MBs and produces semipermeable capsule shells, which allow gas to escape from the MBs without template removal. The MBs-templated strategy can produce highly biocompatible capsules with controllable structure and size, and it is applicable to produce other MPNs systems like BSA-TA-CuII and BSA-TA-NiII . Finally, those MBs-templated MPNs capsules can be further functionalized or modified for the loading of magnetic nanoparticles and the pre-encapsulation of model molecules through covalence or physical adsorption, exhibiting great promise in biomedical applications.

Polypropylene composite hernia mesh with anti-adhesion layer composed of PVA hydrogel and liposomes drug delivery system.

Polypropylene (PP) mesh has been widely used in hernia repair as prosthesis material owing to its excellent balanced biocompatibility and mechanical properties. However, abdominal adhesion between the visceral and PP mesh is still a major problem. Therefore, anti-adhesive PP mesh was designed with poly(vinyl alcohol) (PVA) hydrogel and liposomes drug delivery system. First, PVA hydrogel coating was formed on the surface of PP mesh with freezing-thawing processing cycles (FTP). Subsequently, the lyophilized PVA10-c-PP was immersed in rapamycin (RPM)-loaded liposome solution until swelling equilibrated to obtain the anti-adhesion mesh RPM@LPS/PVA10-c-PP. It was demonstrated that the hydrogel coating can stably fix on the surface of PP mesh even after immersed in PBS solution at 37 °C or 40 °C for up to 30 days. In vitro cell tests revealed the excellent cytocompatibility and the potential to inhibit cell adhesion of the modified PP mesh. Moreover, the anti-adhesive effects of the RPM@LPS/PVA10-c-PP mesh was evaluated through in vivo experiments. The RPM@LPS/PVA10-c-PP mesh exhibited less adhesion than original PP mesh throughout the duration of implantation. At 30 days, the adhesion score of RPM@LPS/PVA10-c-PP mesh was 1.37 ± 0.75, however the original PP was 3 ± 0.71. Furthermore, the results of H&E and Masson trichrome staining proved that the RPM@LPS/PVA10-c-PP mesh showed slighter inflammation response and significant looser fibrous tissue surrounded the PP filaments as compared to the native PP. The current findings manifested that this type of RPM@LPS/PVA10-c-PP might be a potential candidate for anti-adhesion treatment. DATA AVAILABILITY: Data will be made available on request.

Controlling supramolecular filament chirality of hydrogel by co-assembly of enantiomeric aromatic peptides.

Supramolecular chirality plays an indispensable role in living and synthetic systems. However, the generation and control of filament chirality in the supramolecular hydrogel of short peptides remains challenging. In this work, as the first example, we report that the heterodimerization of the enantiomeric mixture controls the alignment, chirality, and stiffness of fibrous hydrogels formed by aromatic building blocks. The properties of the resulting racemic hydrogel could not be achieved by either pure enantiomer. Cryo-EM images indicate that the mixture of L and D enantiomers forms chiral nanofibers, the percentage of which can be readily controlled through stoichiometric co-assembly of heterochiral enantiomers. 2D NOESY NMR and diffusion-ordered NMR spectroscopy reveal that heterodimerization of enantiomers plays a crucial role in the formation of chiral nanofibers. Further mechanistic studies unravel the mechanism of supramolecular chirality formation in this two-component system. Molecular dynamics simulations confirm that the intermolecular hydrogen bond and π-π interaction of heterodimers play important roles in forming a chiral hydrogel. Furthermore, regulation of the adhesion and morphology of mammalian cells is achieved by tuning the relative ratio of L and D enantiomers at the same concentration. This work illustrates a novel strategy to control the supramolecular chirality of aromatic peptide hydrogels for materials science.

Spatiotemporal Control over Chemical Assembly in Living Cells by Integration of Acid-Catalyzed Hydrolysis and Enzymatic Reactions.

Spatiotemporal control of chemical assembly in living cells remains challenging. We have now developed an efficient and general platform to precisely control the formation of assemblies in living cells. We introduced an O-[bis(dimethylamino)phosphono]tyrosine protection strategy in the self-assembly motif as the Trojan horse, whereby the programmed precursors resist hydrolysis by phosphatases on and inside cells because the unmasking of the enzymatic cleavage site occurs selectively in the acidic environment of lysosomes. After demonstrating the multistage self-assembly processes in vitro by liquid chromatography/mass spectrometry (LC-MS), cryogenic electron microscopy (Cryo-EM), and circular dichroism (CD), we investigated the formation of site-specific self-assembly in living cells using confocal laser scanning microscopy (CLSM), LC-MS, and biological electron microscopy (Bio-EM). Controlling chemical assembly in living systems spatiotemporally may have applications in supramolecular chemistry, materials science, synthetic biology, and chemical biology.

Self-Assembling pH-Responsive Nanoparticle Platform Based on Pectin-Doxorubicin Conjugates for Codelivery of Anticancer Drugs.

Pharmaceutical science based on biological nanotechnology is developing rapidly in parallel with the development of nanomaterials and nanotechnology in general. Pectin is a natural polysaccharide obtainable from a wide range of sources. Here, we show that doxorubicin (DOX)-conjugated hydrophilic pectin (PET) comprising an amphiphilic polymer loaded with hydrophobic dihydroartemisinin (DHA) self-assemble into nanoparticles. Importantly, conjugated DOX and DHA could be released quickly in a weakly acidic environment by cleavage of the acid-sensitive acyl hydrazone bond. Confocal microscopy and flow cytometry confirmed that these PET-DOX/DHA nanoparticles efficiently delivered DOX into the nuclei of MCF-7 cells. Significant tumor growth reduction was monitored in a female C57BL/6 mouse model, showing that the PET-DOX/DHA nanoparticle-mediated drug delivery system inhibited tumor growth and may improve therapy. Thus, we have demonstrated that pectin may be useful in the design of materials for biomedical applications.

An efficient prodrug-based nanoscale delivery platform constructed by water soluble eight-arm-polyethylene glycol-diosgenin conjugate.

Drug resistance in tumors is one of the reasons result in the low anticancer efficiency of numerous drugs. Combination therapy has been proven to be a valid way against drug-resistant cancers. However, simply mix the drugs will not only cause many side efforts but also decrease anticancer effect. Herein, a self-assembled nanoparticle platform based on eight-arm-polyethylene glycol-diosgenin (8armPEG-DGN) conjugate was produced for encapsulating another hydrophobic anticancer drug. The 8armPEG-DGN/HCPT NPs were prepared through a simple nanoprecipitation method. The 8armPEG-DGN/HCPT NPs possess suitable size (~107 nm) and high binary drug loading capacity (15.67 wt% of DGN and 14.72 wt% of HCPT). Laser confocal scanning microscopy revealed that 8armPEG-DGN/HCPT NPs significantly increased intracellular uptake toward B16 cells compared with free drugs. Cytotoxicity assay showed the IC50 of 8armPEG-DGN/HCPT NPs were lower than simply mixing DGN and HCPT. In vivo tumor transplantation assay indicated that 8armPEG-DGN/HCPT NPs exhibited superior tumor grown inhibition compared with free drugs and HCPT/DGN Mix. These studies showed that the prepared 8armPEG-DGN/HCPT NPs drug delivery system could serve as a promising candidate for cancer therapy.

pH-Sensitive nanogels based on the electrostatic self-assembly of radionuclide 131I labeled albumin and carboxymethyl cellulose for synergistic combined chemo-radioisotope therapy of cancer.

Development of biocompatible and biodegradable nanocarriers with multiple functionalities has attracted great interest in recent years. In this study, a hybrid hydrogel nanoparticle (nanogel) platform based on the self-assembly of carboxymethyl cellulose (CMC) and bovine serum albumin (BSA) is presented for the first time. It was facile to realize the efficient co-delivery of radionuclide 131I and chemotherapeutic drugs such as camptothecin (CPT) to achieve the combined chemo-radioisotope therapy of cancer. Notably, a nanogel was prepared by a simple and green electrostatic interaction approach, instead of chemical reaction, showing typical spherical shape with average size about 120 nm, high drug loading capacity, robust stability and low hemolysis. Interestingly, such nanogels exhibited pH-dependent drug release profile, leading to significant reduction of damage to normal tissues. Furthermore, the as-prepared nanogels could effectively promote intracellular uptake, prolong blood circulation time and enhance accumulation in the tumor tissues. As a result, an excellent therapeutic effect was achieved both in vitro and in vivo through combined chemo-radioisotope therapy. Collectively, this study presents the preparation of a novel green nanocarrier by a reliable and simple approach, and offers an effective strategy for the combination of chemotherapy and radiotherapy.

Low dose dynamic CT myocardial perfusion imaging using a statistical iterative reconstruction method.

PURPOSE: Dynamic CT myocardial perfusion imaging has the potential to provide both functional and anatomical information regarding coronary artery stenosis. However, radiation dose can be potentially high due to repeated scanning of the same region. The purpose of this study is to investigate the use of statistical iterative reconstruction to improve parametric maps of myocardial perfusion derived from a low tube current dynamic CT acquisition. METHODS: Four pigs underwent high (500 mA) and low (25 mA) dose dynamic CT myocardial perfusion scans with and without coronary occlusion. To delineate the affected myocardial territory, an N-13 ammonia PET perfusion scan was performed for each animal in each occlusion state. Filtered backprojection (FBP) reconstruction was first applied to all CT data sets. Then, a statistical iterative reconstruction (SIR) method was applied to data sets acquired at low dose. Image voxel noise was matched between the low dose SIR and high dose FBP reconstructions. CT perfusion maps were compared among the low dose FBP, low dose SIR and high dose FBP reconstructions. Numerical simulations of a dynamic CT scan at high and low dose (20:1 ratio) were performed to quantitatively evaluate SIR and FBP performance in terms of flow map accuracy, precision, dose efficiency, and spatial resolution. RESULTS: Forin vivo studies, the 500 mA FBP maps gave -88.4%, -96.0%, -76.7%, and -65.8% flow change in the occluded anterior region compared to the open-coronary scans (four animals). The percent changes in the 25 mA SIR maps were in good agreement, measuring -94.7%, -81.6%, -84.0%, and -72.2%. The 25 mA FBP maps gave unreliable flow measurements due to streaks caused by photon starvation (percent changes of +137.4%, +71.0%, -11.8%, and -3.5%). Agreement between 25 mA SIR and 500 mA FBP global flow was -9.7%, 8.8%, -3.1%, and 26.4%. The average variability of flow measurements in a nonoccluded region was 16.3%, 24.1%, and 937.9% for the 500 mA FBP, 25 mA SIR, and 25 mA FBP, respectively. In numerical simulations, SIR mitigated streak artifacts in the low dose data and yielded flow maps with mean error <7% and standard deviation <9% of mean, for 30 × 30 pixel ROIs (12.9 × 12.9 mm(2)). In comparison, low dose FBP flow errors were -38% to +258%, and standard deviation was 6%-93%. Additionally, low dose SIR achieved 4.6 times improvement in flow map CNR(2) per unit input dose compared to low dose FBP. CONCLUSIONS: SIR reconstruction can reduce image noise and mitigate streaking artifacts caused by photon starvation in dynamic CT myocardial perfusion data sets acquired at low dose (low tube current), and improve perfusion map quality in comparison to FBP reconstruction at the same dose.

Reduction of image noise in low tube current dynamic CT myocardial perfusion imaging using HYPR processing: a time-attenuation curve analysis.

PURPOSE: This study describes a HighlY constrained backPRojection (HYPR) image processing method for the reduction of image noise in low tube current time-resolved CT myocardial perfusion scans. The effect of this method on myocardial time-attenuation curve noise and fidelity is evaluated in an animal model, using varying levels of tube current. METHODS: CT perfusion scans of four healthy pigs (42-59 kg) were acquired at 500, 250, 100, 50, 25, and 10 mA on a 64-slice scanner (4 cm axial coverage, 120 kV, 0.4 s∕rotation, 50 s scan duration). For each scan a sequence of ECG-gated images centered on 75% R-R was reconstructed using short-scan filtered back projection (FBP). HYPR processing was applied to the scans acquired at less than 500 mA using parameters designed to maintain the voxel noise level in the 500-mA FBP images. The processing method generates a series of composite images by averaging over a sliding time window and then multiplies the composite images by weighting images to restore temporal fidelity to the image sequence. HYPR voxel noise relative to FBP noise was measured in AHA myocardial segment numbers 1, 5, 6, and 7 at each mA. To quantify the agreement between HYPR and FBP time-attenuation curves (TACs), Bland-Altman analysis was performed on TACs measured in full myocardial segments. The relative degree of TAC fluctuation in smaller subvolumes was quantified by calculating the root mean square deviation of a TAC about the gamma variate curve fit to the TAC data. RESULTS: HYPR image sequences were produced using 2, 7, and 20 beat composite windows for the 250, 100, and 50 mA scans, respectively. At 25 and 10 mA, all available beats were used in the composite (41-60; average 50). A 7-voxel-wide 3D cubic filter kernel was used to form weighting images. The average ratio of HYPR voxel noise to 500-mA FBP voxel noise was 1.06, 1.10, 0.97, 1.11, and 2.15 for HYPR scans at 250, 100, 50, 25, and 10 mA. The average limits-of-agreement between HYPR and FBP TAC values measured 0.02+∕-0.91, 0.04+∕-1.92, 0.19+∕-1.59, 1.13+∕-4.22, and 1.07+∕-6.37 HU (mean difference +∕-1.96 SD). The HYPR image subvolume that yielded a fixed level of TAC fluctuations was smaller, on average, than the FBP subvolume determined at the same mA. CONCLUSIONS: HYPR processing is a feasible method for generating low noise myocardial perfusion data from a low-mA time-resolved CT myocardial perfusion scan. The method is applicable to current clinical scanners and uses conventional image reconstructions as input data.

Radiation dose reduction in time-resolved CT angiography using highly constrained back projection reconstruction.

Recently dynamic, time-resolved three-dimensional computed tomography angiography (CTA) has been introduced to the neurological imaging community. However, the radiation dose delivered to patients in time-resolved CTA protocol is a high and potential risk associated with the ionizing radiation dose. Thus, minimizing the radiation dose is highly desirable for time-resolved CTA. In order to reduce the radiation dose delivered during dynamic, contrast-enhanced CT applications, we introduce here the CT formulation of HighlY constrained back PRojection (HYPR) imaging. We explore the radiation dose reduction approaches of both acquiring a reduced number of projections for each image and lowering the tube current used during acquisition. We then apply HYPR image reconstruction to produce image sets at a reduced patient dose and with low image noise. Numerical phantom experiments and retrospective analysis of in vivo canine studies are used to assess the accuracy and quality of HYPR reduced dose image sets and validate our approach. Experimental results demonstrated that a factor of 6-8 times radiation dose reduction is possible when the HYPR algorithm is applied to time-resolved CTA exams.