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Polypyrrole (PPy) nanoparticles have been widely studied in tumor photothermal therapy (PTT) for their significant photostability, good biocompatibility, and excellent photothermal performance. Herein, we report bovine serum albumin (BSA) stabilized PPy that were mineralized by MnO2 nanozyme on the surface (PPy@BSA-MnO2) to achieve synergistic photothermal and chemodynamic therapy (CDT) for breast cancer. In this multifunctional nanoplatform, the surface-loaded MnO2 undergoes a redox reaction with glutathione (GSH) to generate glutathione disulfide (GSSG) and Mn2+. Then, Mn2+ can convert H2O2 into a highly cytotoxic ˙OH to achieve chemodynamic therapy (CDT) and possess good magnetic resonance (MR) T1-weighted imaging capabilities to realize contrast imaging of the 4T1 tumor-bearing mouse models. In addition, PPy nanoparticles can efficiently convert near-infrared light energy into heat and achieve PTT. Most importantly, PPy@BSA-MnO2 nanoprobes have excellent in vitro 4T1 cell-killing effect and in vivo tumor-suppressive properties. The acute toxicity assessment results indicate that PPy@BSA-MnO2 nanoprobes have good biological safety. Therefore, the as-prepared multifunctional PPy@BSA-MnO2 nanoprobes possess excellent performance to promote MRI-guided PTT/CDT synergistic therapy for breast cancer treatment and have extensive clinical transformation and application prospects.

Lei Yang,1,2,* Xiafei Li,3,* Yiting Wu,4 Pengchong Du,1,5 Lulu Sun,1 Zhenyang Yu,2 Shuang Song,1 Jianshen Yin,1 Xianfen Ma,1 Changqin Jing,1 Junqiang Zhao,3 Hongli Chen,1 Yuzhen Dong,2 Qiqing Zhang,1 Liang Zhao1,6,7 1College of Life Science and Technology, Xinxiang Medical University, Xinxiang, People’s Republic of China; 2Department of Orthopedics, First Affiliated Hospital, Xinxiang Medical University, Xinxiang, People’s Republic of China; 3College of Medical Engineering, Xinxiang Medical University, Xinxiang, People’s Republic of China; 4Xiacun Community Health Service Center, Shenzhen Hospital, University of Chinese Academy of Sciences, Shenzhen, People’s Republic of China; 5Department of Cardio-Thoracic Surgery, Third Affiliated Hospital, Xinxiang Medical University, Xinxiang, People’s Republic of China; 6Key Laboratory of Cardiac Structure Research, Zhengzhou Seventh People’s Hospital, Zhengzhou, People’s Republic of China; 7The Central Lab, The Third People’s Hospital of Datong, Datong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liang Zhao; Yuzhen Dong Email zhaoliang4321@163.com; dongyuzhen1998@163.comPurpose: The development of tissue-engineered blood vessels provides a new source of donors for coronary artery bypass grafting and peripheral blood vessel transplantation. Fibrin fiber has good biocompatibility and is an ideal tissue engineering vascular scaffold, but its mechanical property needs improvement.Methods: We mixed polyurethane (PU) and fibrin to prepare the PU/fibrin vascular scaffolds by using electrospinning technology in order to enhance the mechanical properties of fibrin scaffold. We investigated the morphological, mechanical strength, hydrophilicity, degradation, blood and cell compatibility of PU/fibrin (0:100), PU/fibrin (5:95), PU/fibrin (15:85) and PU/fibrin (25:75) vascular scaffolds. Based on the results in vitro, PU/fibrin (15:85) was selected for transplantation in vivo to repair vascular defects, and the extracellular matrix formation, vascular remodeling, and immune response were evaluated.Results: The results indicated that the fiber diameter of the PU/fibrin (15:85) scaffold was about 712nm. With the increase of PU content, the mechanical strength of the composite scaffolds increased, however, the degradation rate decreased gradually. The PU/fibrin scaffold showed good hydrophilicity and hemocompatibility. PU/fibrin (15:85) vascular scaffold could promote the adhesion and proliferation of mesenchymal stromal cells (MSCs). Quantitative RT-PCR experimental results showed that the expression of collagen, survivin and vimentin genes in PU/fibrin (15:85) was higher than that in PU/fibrin (25:75). The results in vivo indicated the mechanical properties and compliance of PU/fibrin grafts could meet clinical requirements and the proportion of thrombosis or occlusion was significantly lower. The graft showed strong vasomotor response, and the smooth muscle cells, endothelial cells, and ECM deposition of the neoartery were comparable to that of native artery after 3 months. At 3 months, the amount of macrophages in PU/fibrin grafts was significantly lower, and the secretion of pro-inflammatory and anti-inflammatory cytokines decreased.Conclusion: PU/fibrin (15:85) vascular scaffolds had great potential to be used as small-diameter tissue engineering blood vessels.Keywords: PU/fibrin scaffold, small diameter, in vitro biocompatibility, biomechanical properties, vascular remodeling

Die Mikro- und Nanomesstechnik wird vorangetrieben durch die stetigen Fortschritte der Fertigungstechnik. Die Messaufgaben für Mikro- und Nanomesssysteme sind geprägt von zunehmend sinkenden Strukturgrößen und Miniaturisierung der Merkmale bei zugleich zunehmender Dimensionalität. Hochauflösende Messinstrumente und Techniken zur Qualitätssicherung im Mikro- und Nanometerbereich erfordern sowohl quantitative, dimensionale Messungen mit Nanometergenauigkeit als auch Messungen über große Messbereiche, um die Nanotechnologie zu einer industriellen Nutzung zu führen. Weißlichtinterferometrie und Rasterkraftmikroskopie sind zwei wichtige Messverfahren der Mikro- und Nanomesstechnik. Allerdings sind ihre Messbereiche begrenzt. Es ist von großer Bedeutung, dass die Messbereiche bis zu mehreren Millimetern erweitert werden, um die heutigen metrologischen Herausforderungen zu erfüllen. Die vorliegende Arbeit zeigt das Vorgehen für die großflächige Topografiemessung mit hoher Strukturauflösung mittels Weißlichtinterferometrie und Rasterkraftmikroskopie. Ein Weißlichtinterferenzmikroskop wurde in die Nanopositionier- und Nanomessmaschine (NMM-1) zur großflächigen Topografiemessung auch ohne Überlappungsfelder integriert. Der Messaufbau, die Einmessstrategie, die Charakterisierung der metrologischen Eigenschaften, die Korrektur von Kippungen bzw. Drehung des Sensors um die lateralen Achsen und die vertikale Achse und eine experimentelle Untersuchung zur Verifizierung der Messstrategie werden aufgezeigt. Ein neues metrologisches Rasterkraftmikroskop für gleichzeitige Messung der Biegung, Torsion und Position des Cantilevers mit verbesserter Signalqualität, welches ebenfalls in die NMM-1 für großflächige Topografiemessungen integriert wurde, wird vorgestellt. Dabei werden der Messaufbau, die Einmessstrategie, die Charakterisierung, die Messunsicherheit und Applikationsmessungen wie Stufenhöhenmessung, Gitterabstandsbestimmung und großflächige Messungen gezeigt., Micro- and nano measuring technology is driven by the continuous advances in manufacturing technology. The measurement tasks for micro- and nanomeasuring systems are characterized by continually decreasing structure sizes and miniaturization of the features with simultaneously increasing dimensions. Measuring instruments and technologies with high-resolution for quality assurance in the micro- and nanometer range require both quantitative, dimensional measurements with nanometer accuracy and measurements over large measuring ranges for the application of the nanotechnology in industry. White light interferometry and atomic force microscopy are two important measuring methods in micro- and nano measuring technology. However, their measuring ranges are limited. It is very important that the measuring ranges are extended up to several millimeters in order to meet current metrological challenges. The present work shows the methods for large-area topography measurement with high structural resolution using white light interferometry and atomic force microscopy. A white light interferometric microscope was integrated into the nanopositioning and nanomeasuring machine (NMM-1) for large-area topography measurements even without overlapping fields. The measurement setup, the measuring strategy, the characterization of the metrological properties, the correction of sensor tilts or rotation about the lateral axes and the vertical axis and an experimental investigation to verify the measurement strategy are presented. A new metrological atomic force microscope for simultaneous measurement of bending, torsion and position of the cantilever with improved signal quality that was also integrated into the NMM-1 for large-area topography measurements is presented. The measurement setup, the measuring strategy, the characterization, the measurement uncertainty and applications of measurement such as step height measurement, pitch determination and large-area measurements are shown., FAU Studien aus dem Maschinenbau; 390