Effects of a Matrix Metalloproteinase Inhibitor-Eluting Stent on In-Stent Restenosis.

BACKGROUND The aim of this study was to compare changes in the extracellular matrix after implantation of a stent that elutes a matrix metalloproteinase (MMP) inhibitor (GM6001); and to determine the effects of the GM6001-eluting stent upon prevention of in-stent restenosis (ISR). MATERIAL AND METHODS We included 48 Guangxi Bama mini-pigs in this study. A GM6001-eluting stent was placed in one iliac artery and a stent that did not elute GM6001 was placed in the contralateral iliac artery. The iliac arteries were removed at 6 hours as well as 1, 7, 14, 56, 84, and 336 days after stent placement. Arteries were analyzed for morphometry, gelatinase content, different phenotypes of vascular smooth muscle cells (VSMCs), collagen content, apoptotic rate, and cell density. RESULTS The vascular lumen areas of the GM6001 group were significantly increased and the neointimal areas were significantly reduced compared with the control group from the 7 days to the 336 days. In the 2 groups, expression of MMP-2 and MMP-9 peaked simultaneously, but GM6001-eluting stents inhibited expression of MMP-2 and MMP-9 in the vascular media and neointima (especially around the struts) significantly. In the GM6001 group, expression of tissue inhibitor of matrix metalloproteinase (TIMP)-1, TIMP-2, myosin heavy chain 10 (MYH-10, marker of the proliferative phenotype of VSMCs), collagen content, percentage of apoptotic cells, and cell density were also decreased significantly compared with those in the control group. CONCLUSIONS Use of GM6001-eluting stents resulted in persistent and potent inhibition of intimal hyperplasia, an increase in luminal area, and no obvious thrombosis in the arteries of the mini-pigs.

Recent advances of self-assembling peptide-based hydrogels for biomedical applications.

Peptide-based hydrogels have been proven to be preeminent biomedical materials due to their high water content, tunable mechanical stability, great biocompatibility and excellent injectability. The ability of peptide-based hydrogels to provide extracellular matrix-mimicking environments opens up opportunities for their biomedical applications in fields such as drug delivery, tissue engineering, and wound healing. In this review, we first describe several methods commonly used for the fabrication of robust peptide-based hydrogels, including spontaneous hydrogelation, enzyme-controlled hydrogelation and cross-linking-enhanced hydrogelation. We then introduce some representative studies on their applications in drug delivery and antitumor therapy, antimicrobial and wound healing materials, and 3D bioprinting and tissue engineering. We hope that this review facilitates the advances of hydrogels in biomedical applications.

Hydrogel Nanoarchitectonics of a Flexible and Self-Adhesive Electrode for Long-Term Wireless Electroencephalogram Recording and High-Accuracy Sustained Attention Evaluation.

Hydrogels are ideal building blocks to fabricate the next generation of electrodes for acquiring high-quality physiological electrical signals, for example, electroencephalography (EEG). However, collection of EEG signals still suffers from electrode deformation, sweating, extensive body motion and vibration, and environmental interference. Herein, polyvinyl alcohol and polyvinylpyrrolidone are selected to prepare a hydrogel network with tissue-like modulus and excellent flexibility. Additionally, polydopamine nanoparticles, obtained by polydopamine peroxidation, are integrated into the hydrogel to endow them with higher transparency, higher self-adhesion, and lower impedance. Consequently, a multichannel and wirelessly operated hydrogel electrode can establish a conformal and stable interface with tissue and illustrate high channel uniformity, low interfacial contact impedance, low power noise, long-term stability, and a tolerance to sweat and motion. Furthermore, the hydrogel electrode shows the unprecedented ability to classify the recorded high-quality prefrontal EEG signals into seven-category sustained attention with high accuracy (91.5%), having great potential applications in the assessment of human consciousness and in multifunctional diagnoses.

Low-power upconversion in dye-doped polymer nanoparticles.

Examples of nanoscale low-power upconverting systems are rapidly increasing because of their potential application in numerous areas such as bioimaging or drug delivery. The fabrication of dye-doped cross-linked rubbery nanoparticles that exhibit upconversion even at relatively low power densities is reported here. The nanoparticles were prepared by surfactant-free emulsion polymerization of n-butylacrylate with divinylbenzene as a cross-linker, followed by dyeing of the resulting particles with a two-chromophore system composed of a palladium porphyrin sensitizer, and diphenylanthracene. Blue emission (≈440 nm) of these systems was observed upon excitation at 532 nm. In addition to their optical properties, the particles were characterized by electron microscopy and dynamic light scattering.

In situ synthesis of superorganism-like Au NPs within microgels with ultra-wide absorption in visible and near-infrared regions for combined cancer therapy.

The whole is a collection of parts and fulfills specific functions that the parts do not have. In this work, 50 nm Au NPs were in situ synthesized and close packed into a superorganism-like superstructure by means of microgel 3D networks. The combined microgel is endowed with ultra-wide absorption in visible and near-infrared regions between 500 and 1100 nm in spite of Au NPs not having this property. The strong collective plasmon coupling between neighboring Au NPs induces high photothermal conversion efficiency of the microgel system under irradiation at various laser wavelengths. Due to the good loading capability, microgels with nanocomposites can also load photosensitive drugs simultaneously and be used for combined cancer treatments of photothermal therapy and photodynamic therapy.

Using hydrogel microparticles to transfer hydrophilic nanoparticles and enzymes to organic media via stepwise solvent exchange.

We present a simple and versatile approach of using hydrogel microparticles to transfer both inorganic hydrophilic nanoparticles (NPs) such as CdTe quantum dots and enzymes such as lipase B from Candida antarctica (CalB) to organic media and eventually encapsulate them in the gel microparticles by consecutive exchange of the water swollen in the hydrogel microparticles with water-miscible organic solvents and water-immiscible solvents. The entrapment of hydrophilic nanoparticles is due to their incompatibility with water-immiscible organic solvents soaked in the gel matrices and in the surrounding environment, so the present approach obviates the need for any chemical modification to the NP surface or to the hydrogel and furthermore does not require any size matching or chemical affinity of the NPs for the hydrogel networks. The solvent exchange process causes little change of the intrinsic properties of hydrophilic nanoparticles; CdTe quantum dots encapsulated in hydrogel microparticles, dispersed in water-immiscible organic solvents, remain strongly fluorescent, and CalB retains high catalytic activity. Of importance is that the hydrophilic nanoparticles encapsulated in the gel microparticles in organic media can be completely recovered in aqueous media via reversed solvent exchange. As a consequence, the present approach should hold immense promise for technical applications, especially in catalysis.

Dipeptide Self-assembled Hydrogels with Shear-Thinning and Instantaneous Self-healing Properties Determined by Peptide Sequences.

Dipeptide self-assembled hydrogels have potential biomedical applications because of their great biocompatibility, bioactivity, and tunable physicochemical properties, which can be modulated in the molecular level by design of amino acid sequences. Herein, a series of dipeptides (Fmoc-FL, -YL, -LL, and -YA) are designed to form shear-thinning hydrogels with self-healing and tunable mechanical properties by adjusting the synergetic effect of hydrophobic interactions (π-π stacking and hydrophobic effect) and hydrogen bonds of peptides through substitution of amino acid residues. The enhancement of hydrophobic interactions is a primary factor to promote mechanical rigidity of hydrogels, and strong hydrogen-bonding interactions between molecules contribute to the instantaneous self-healing property, which is supported by experimental studies (FTIR, CD, SEM, AFM, and rheology) and molecular dynamics simulations. The injectable dipeptide hydrogels were certified as an ideal endoscopic submucosal dissection filler to make operation convenient and secure in mice and living mini-pig's experiments with a longer duration time, higher stiffness, and lower inflammatory response than commercial clinical fillers.

Thermal stability and in vitro bioactivity of Ti-Al-V-O nanostructures fabricated on Ti6Al4V alloy.

This work investigates the thermal stability and in vitro bioactivity of Ti-Al-V-O nanostructures grown on Ti6Al4V alloy through an anodization method. After anodization of the two-phase Ti6Al4V alloy, there were two different kinds of Ti-Al-V-O nanostructure (nanotube arrays grown in the alpha-phase region and irregular nanopores grown in the beta-phase region) that formed on the surface of the alloy. It was found that the Ti-Al-V-O nanotubes can withstand a high temperature of 675 degrees C in air without collapse, whereas the irregular Ti-Al-V-O nanopores presented a lower thermal stability. In vitro simulated body fluid (SBF) testing of heat-treated nanostructures indicated that a quick apatite formation on these nanostructures occurred after only several hours of sample immersion in the SBF.

Anodic fabrication and bioactivity of Nb-doped TiO2 nanotubes.

We report anodic formation of Ti-Nb-O nanotubes on top of a Ti35Nb alloy, and in vitro bioactivity and stem cell response of the anodic nanotubes. It was found that the amorphous Ti-Nb-O nanotubes presented a significantly enhanced in vitro bioactivity (in simulated body fluids) compared to those of undoped TiO2 nanotubes and porous Ti-Nb-O without nanotubular structure. Similar to undoped TiO2 nanotubes, the Ti-Nb-O nanotubes also promote mesenchymal stem cell adhesion and fast formation of extracellular matrix (ECM) materials. The above findings make it possible to further explore the biological properties, such as cell proliferation and drug delivery, of a variety of Ti-alloy-based oxide nanotubes.

Hydrogen-bond-selective phase transfer of nanoparticles across liquid/gel interfaces.

In the swim: Colloidal nanoparticles coated with polylactide (PLA, red) and poly(ethylene glycol) brushes (PEG, black) can transfer from organic to aqueous phases across liquid/liquid or liquid/gel interfaces during degradation of the PLA coating (see picture: first step), which is driven selectively by the hydrogen bonding of the PEG coating with the aqueous phase (second step).

An Examination of Differences in the New Bone Formation Promoted by Different Doses of Recombinant Human Parathyroid Hormone during Mandibular Distraction Osteogenesis.

BACKGROUND: The administration of different doses of parathyroid hormone to promote mandibular distraction osteogenesis remains unclear. The objective of the present study was to examine the effects of recombinant human parathyroid hormone on new bone formation during mandibular distraction osteogenesis and to investigate the dose-effect relationship associated with this phenomenon. METHODS: A total of 45 rabbits were used to establish the mandibular distraction osteogenesis model. The rabbits were divided into a control group (that received a subcutaneous injection of 1 ml of saline every other day) and experimental groups A, B, C, and D (that received subcutaneous injections of 10, 20, 30, and 40 µg/kg of recombinant human parathyroid hormone, respectively, every other day). On days 1, 7, and 14 of the consolidation period after the distraction had been completed, new bone in the distraction region was examined through histomorphometric investigation and bone mineral density testing. RESULTS: On days 1, 7, and 14 of the fixation period, the number of osteoblasts, trabecular bone area, and bone mineral density were greater in each experimental group than in the control group. On day 1 of the consolidation period, group C featured the highest average number of osteoblasts. On day 14 of the consolidation period, group C exhibited the highest bone mineral densities and largest trabecular bone areas. CONCLUSIONS: Intermittent subcutaneous injections of recombinant human parathyroid hormone can promote new bone formation during mandibular distraction osteogenesis. Different doses of recombinant human parathyroid hormone promoted mandibular distraction osteogenesis to differing extents.