Two-year follow-up of a randomized multicenter study comparing a drug-coated balloon with a drug-eluting stent in native small coronary vessels: The RESTORE Small Vessel Disease China trial.

OBJECTIVES: To report the clinical outcomes of the RESTORE drug-coated balloon (DCB; Cardionovum, Bonn, Germany) for treatment of de novo small vessel disease (SVD) beyond 1 year. BACKGROUND: Previous reports have demonstrated the noninferiority of the RESTORE DCB to the RESOLUTE Integrity drug-eluting stent (DES; Medtronic, Minneapolis, Minnesota) in terms of 9-month in-segment percent diameter stenosis. METHODS: In the prospective, multicenter, noninferiority RESTORE SVD China trial, 230 patients with visually-estimated reference vessel diameter (RVD) ≥2.25 and ≤2.75 mm were randomized to DCB or DES in a 1:1 ratio stratified by diabetes and number of lesions treated. Furthermore, 32 patients with RVD ≥2.00 and <2.25 mm were enrolled in a nested very small vessel (VSV) registry. Clinical follow-up were performed at 2 years to evaluate target lesion failure (TLF) in both groups and the VSV cohort. RESULTS: Overall, 256 (97.7%) patients (115 and 109 in the DCB and DES groups, respectively, and 32 in the VSV cohort) completed 2 years of follow-up. There was no significant difference in TLF between the DCB and DES groups (5.2 vs. 3.7%, p = .75). Target lesion revascularization was acceptable at 1 month, 1 year, and 2 years, and did not differ significantly with DCB from that in the DES group (0.9 vs. 0%, p = 1.0, 4.4 vs. 2.6%, p = .72, 5.2 vs. 2.8%, p = .50, respectively). CONCLUSIONS: Compared to the second-generation DES, the RESTORE DCB did not increase the risk of clinical outcomes. Late catch-up phenomen requiring revascularization was not significant in this study.

In vivo self-assembled shape-memory polyurethane for minimally invasive delivery and therapy.

Advanced elastomers are highly in demand for the fabrication of medical devices for minimally invasive surgery (MIS). Herein, a shape memory and self-healing polyurethane (PCLUSe) composed of semi-crystalline poly(ε-caprolactone) (PCL) segments and interchangeable and antioxidative diselenide bonds was designed and synthesized. The excellent shape memory of PCLUSe contributed to the smooth MIS operation, leading to less surgical wounds than in the case of sternotomy. The diselenide bonds of PCLUSe contributed to the rapid self-healing under 405 nm irradiation within 60 s, and the alleviation of tissue oxidation post injury. After being delivered through a 10 mm diameter trocar onto a beating canine heart by MIS, two shape-recovered PCLUSe films self-assembled (self-healing) into a larger single patch (20 × 10 × 0.2 mm3) under the trigger of laser irradiation in situ, which could efficiently overcome the limited-size problem within MIS and meet a larger treatment area. The diselenide bonds in the PCLUSe cardiac patches protected the myocardium under oxidative stress post myocardial infarction (MI), and significantly maintained the cardiac functions.

Enhanced cancer therapeutic efficiency of NO combined with siRNA by caspase-3 responsive polymers.

The combination of nitric oxide (NO) and siRNA is highly desirable for cancer therapy. Here, the furoxans-grafted PEI polymer (FDP) with caspase-3 responsive cleavable DEVD linker was synthesized, and used to bind siRNAs via electrostatic interaction and self-assembled into FDP/siRNA nanoplexes by hydrophobic force. After cellular uptake and lysosomal escape, the FDP/siRNA nanoplexes could achieve GSH-triggered NO release, and then increase the activity of caspase-3. The activated caspase-3 could specifically cleave the DEVD peptide sequence and enhance cell apoptosis. With the cleavage of DEVD peptide sequence, the disassembly of FDP/siRNA nanoplexes was further promoted, thereby resulting in increased siRNAs of ~40% were released at 48 h compared with the caspase-3 non-responsive FDnP/siRNA nanoplexes. By this way, cell apoptosis promotion and cell proliferation inhibition was achieved by siRNA-based downregulation of EGFR protein and the upregulated activity of caspase-3, followed by the enhanced cascade release of NO from FDP/siRNA nanoplexes. Furthermore, in vivo results demonstrated the improved anti-cancer efficiency of FDP/siEGFR nanoplexes without any detectable side effects. Therefore, it is believed that the caspase-3 responsive cleavable furoxans-grafted PEI polymers could provide a potential and efficient enhancement for cancer therapeutic efficiency by the co-delivery of nitric oxide and siRNA.

Super-quenched Molecular Probe Based on Aggregation-Induced Emission and Photoinduced Electron Transfer Mechanisms for Formaldehyde Detection in Human Serum.

Energy transfer between fluorescent dyes and quenchers is widely used in the design of light-up probes. Although dual quenchers are more effective in offering lower background signals and higher turn-on ratios than one quencher, such probes are less explored in practice as they require both quenchers to be within the proximity of the fluorescent core. In this contribution, we utilized intramolecular motion and photoinduced electron transfer (PET) as quenching mechanisms to build super-quenched light-up probes based on fluorogens with aggregation-induced emission. The optimized light-up probe possesses negligible background and is able to detect not only free formaldehyde (FA) but also polymeric FA, with an unprecedented turn-on ratio of >4900. We envision that this novel dual quenching strategy will help to develop various light-up probes for analyte sensing.

Optical coherence tomography assessment of a PLGA-polymer with electro-grafting base layer versus a PLA-polymer sirolimus-eluting stent at three-month follow-up: the BuMA-OCT randomised trial.

AIMS: To compare stent strut coverage using optical coherence tomography (OCT) at three-month follow-up between a PLGA-polymer with electro-grafting base layer sirolimus-eluting stent (SES) (BuMA) and a PLA-polymer SES (EXCEL). METHODS AND RESULTS: This prospective, single-centre, non-inferiority randomised BuMA-OCT trial enrolled patients with de novo coronary artery lesions, treated with either the BuMA or the EXCEL stent. The study primary endpoint was OCT-evaluated stent strut coverage at three months. Secondary endpoints were neointimal thickness of stent struts, and incomplete stent apposition evaluated with OCT. A total of 80 patients were randomly assigned to receive the BuMA (n=40) or the EXCEL (n=40) stent. In OCT follow-up (achieved in 86.3% of cases: BuMA, n=33; EXCEL, n=36), the percentage of stent strut coverage was significantly higher in the BuMA vs. the EXCEL group (strut level: 94.2% vs. 90.0%, p<0.01; p(non-inferiority)<0.0001; p(superiority) <0.0001), while the proportion of malapposed struts (strut level: 1.28% vs. 1.80%, p=0.51) and the mean neointimal thickness (strut level: 0.07±0.03 mm vs. 0.06±0.02 mm, p=0.31) were similar. Rates of myocardial infarction (periprocedural non-Q-wave, 7.5% vs. 7.5%, p=1.00) and target lesion failure (7.5% vs. 7.5%, p=1.00) were similar between groups, with no cardiac death or stent thrombosis. CONCLUSIONS: In the BuMA-OCT randomised trial, the novel BuMA PLGA-polymer with electro-grafting base layer SES was superior to the EXCEL PLA-polymer SES in the primary endpoint of stent strut coverage at three-month follow-up.

Synthesis and anticoagulation activities of polymer/functional graphene oxide nanocomposites via Reverse Atom Transfer Radical Polymerization (RATRP).

The anticoagulation properties of biomaterials are crucial for biomedical applications, especially for blood-contacting materials. In this work, a range of functional graphene oxide based on the biomimetic monomer 2-(methacryloyloxy) ethyl phosphorylcholine (GO-g-pMPC) were synthesized by RATRP in alcoholic media using peroxide groups as initiator, and then filled into the polyurethane matrix to obtain the polyurethane (PU)/functional graphene oxide nanocomposite films (PU/GO-g-pMPC). The tensile strength and elongation and morphology of the PU/GO-g-pMPC were characterized by mechanical properties test, Transmission electron microscope (TEM), respectively. The results showed that a small amount of graphene oxide can improve the mechanical properties of PU. The blood compatibility of the PU substrates was evaluated by protein adsorption tests and platelet adhesion tests in vitro. It was found that all the PU/GO-g-pMPC showed improved resistance to nonspecific protein adsorption and platelet adhesion.