TY - JOUR A1 - Li, Zhengdong A1 - Xu, Xun A1 - Wang, Weiwei A1 - Kratz, Karl A1 - Sun, Xianlei A1 - Zou, Jie A1 - Deng, Zijun A1 - Jung, Friedrich Wilhelm A1 - Gossen, Manfred A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Modulation of the mesenchymal stem cell migration capacity via preconditioning with topographic microstructure JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - Controlling mesenchymal stem cells (MSCs) behavior is necessary to fully exploit their therapeutic potential. Various approaches are employed to effectively influence the migration capacity of MSCs. Here, topographic microstructures with different microscale roughness were created on polystyrene (PS) culture vessel surfaces as a feasible physical preconditioning strategy to modulate MSC migration. By analyzing trajectories of cells migrating after reseeding, we demonstrated that the mobilization velocity of human adipose derived mesenchymal stem cells (hADSCs) could be promoted by and persisted after brief preconditioning with the appropriate microtopography. Moreover, the elevated activation levels of focal adhesion kinase (FAK) and mitogen-activated protein kinase (MAPK) in hADSCs were also observed during and after the preconditioning process. These findings underline the potential enhancement of in vivo therapeutic efficacy in regenerative medicine via transplantation of topographic microstructure preconditioned stem cells. KW - Mesenchymal stem cells KW - precondition KW - microstructure KW - migration KW - FAK-MAPK Y1 - 2017 U6 - https://doi.org/10.3233/CH-179208 SN - 1386-0291 SN - 1875-8622 VL - 67 SP - 267 EP - 278 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Zou, Jie A1 - Wang, Weiwei A1 - Neffe, Axel T. A1 - Xu, Xun A1 - Li, Zhengdong A1 - Deng, Zijun A1 - Sun, Xianlei A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Adipogenic differentiation of human adipose derived mesenchymal stem cells in 3D architectured gelatin based hydrogels (ArcGel) JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - Polymeric matrices mimicking multiple functions of the ECM are expected to enable a material induced regeneration of tissues. Here, we investigated the adipogenic differentiation of human adipose derived mesenchymal stem cells (hADSCs) in a 3D architectured gelatin based hydrogel (ArcGel) prepared from gelatin and L-lysine diisocyanate ethyl ester (LDI) in an one-step process, in which the formation of an open porous morphology and the chemical network formation were integrated. The ArcGel was designed to support adipose tissue regeneration with its 3D porous structure, high cell biocompatibility, and mechanical properties compatible with human subcutaneous adipose tissue. The ArcGel could support initial cell adhesion and survival of hADSCs. Under static culture condition, the cells could migrate into the inner part of the scaffold with a depth of 840 +/- 120 mu m after 4 days, and distributed in the whole scaffold (2mm in thickness) within 14 days. The cells proliferated in the scaffold and the fold increase of cell number after 7 days of culture was 2.55 +/- 0.08. The apoptotic rate of hADSCs in the scaffold was similar to that of cells maintained on tissue culture plates. When cultured in adipogenic induction medium, the hADSCs in the scaffold differentiated into adipocytes with a high efficiency (93 +/- 1%). Conclusively, this gelatin based 3D scaffold presented high cell compatibility for hADSC cultivation and differentiation, which could serve as a potential implant material in clinical applications for adipose tissue reparation and regeneration. KW - Mesenchymal stem cells KW - gelatin based scaffold KW - adipose tissue regeneration KW - adipogenic differentiation Y1 - 2017 U6 - https://doi.org/10.3233/CH-179210 SN - 1386-0291 SN - 1875-8622 VL - 67 IS - 3-4 SP - 297 EP - 307 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Tung, Wing Tai A1 - Sun, Xianlei A1 - Wang, Weiwei A1 - Xu, Xun A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Structure, mechanical properties and degradation behavior of electrospun PEEU fiber meshes and films JF - MRS advances : a journal of the Materials Research Society (MRS) N2 - The capability of a degradable implant to provide mechanical support depends on its degradation behavior. Hydrolytic degradation was studied for a polyesteretherurethane (PEEU70), which consists of poly(p-dioxanone) (PPDO) and poly(epsilon-caprolactone) (PCL) segments with a weight ratio of 70:30 linked by diurethane junction units. PEEU70 samples prepared in the form of meshes with average fiber diameters of 1.5 mu m (mesh1.5) and 1.2 mu m (mesh1.2), and films were sterilized and incubated in PBS at 37 degrees C with 5 vol% CO2 supply for 1 to 6 weeks. Degradation features, such as cracks or wrinkles, became apparent from week 4 for all samples. Mass loss was found to be 11 wt%, 6 wt%, and 4 wt% for mesh1.2, mesh1.5, and films at week 6. The elongation at break decreased to under 20% in two weeks for mesh1.2. In case of the other two samples, this level of degradation was achieved after 4 weeks. The weight average molecular weight of both PEEU70 mesh and film samples decreased to below 30 kg/mol when elongation at break dropped below 20%. The time period of sustained mechanical stability of PEEU70-based meshes depends on the fiber diameter and molecular weight. Y1 - 2021 U6 - https://doi.org/10.1557/s43580-020-00001-0 SN - 2059-8521 VL - 6 IS - 10 SP - 276 EP - 282 PB - Springer Nature Switzerland AG CY - Cham ER - TY - JOUR A1 - Tung, Wing Tai A1 - Maring, Janita A. A1 - Xu, Xun A1 - Liu, Yue A1 - Becker, Matthias A1 - Somesh, Dipthi Bachamanda A1 - Klose, Kristin A1 - Wang, Weiwei A1 - Sun, Xianlei A1 - Ullah, Imran A1 - Kratz, Karl A1 - Neffe, Axel T. A1 - Stamm, Christof A1 - Ma, Nan A1 - Lendlein, Andreas T1 - In vivo performance of a cell and factor free multifunctional fiber mesh modulating postinfarct myocardial remodeling JF - Advanced Functional Materials N2 - Guidance of postinfarct myocardial remodeling processes by an epicardial patch system may alleviate the consequences of ischemic heart disease. As macrophages are highly relevant in balancing immune response and regenerative processes their suitable instruction would ensure therapeutic success. A polymeric mesh capable of attracting and instructing monocytes by purely physical cues and accelerating implant degradation at the cell/implant interface is designed. In a murine model for myocardial infarction the meshes are compared to those either coated with extracellular matrix or loaded with induced cardiomyocyte progenitor cells. All implants promote macrophage infiltration and polarization in the epicardium, which is verified by in vitro experiments. 6 weeks post-MI, especially the implantation of the mesh attenuates left ventricular adverse remodeling processes as shown by reduced infarct size (14.7% vs 28-32%) and increased wall thickness (854 mu m vs 400-600 mu m), enhanced angiogenesis/arteriogenesis (more than 50% increase compared to controls and other groups), and improved heart function (ejection fraction = 36.8% compared to 12.7-31.3%). Upscaling as well as process controls is comprehensively considered in the presented mesh fabrication scheme to warrant further progression from bench to bedside. KW - bioinstructive materials KW - cardiac regeneration KW - function by structure; KW - modulation of in vivo regeneration KW - multifunctional biomaterials Y1 - 2022 U6 - https://doi.org/10.1002/adfm.202110179 SN - 1616-301X SN - 1616-3028 VL - 32 IS - 31 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Sun, Xun A1 - Lall, Upmanu A1 - Merz, Bruno A1 - Nguyen Viet Dung, T1 - Hierarchical Bayesian clustering for nonstationary flood frequency analysis: Application to trends of annual maximum flow in Germany JF - Water resources research N2 - Especially for extreme precipitation or floods, there is considerable spatial and temporal variability in long term trends or in the response of station time series to large-scale climate indices. Consequently, identifying trends or sensitivity of these extremes to climate parameters can be marked by high uncertainty. When one develops a nonstationary frequency analysis model, a key step is the identification of potential trends or effects of climate indices on the station series. An automatic clustering procedure that effectively pools stations where there are similar responses is desirable to reduce the estimation variance, thus improving the identification of trends or responses, and accounting for spatial dependence. This paper presents a new hierarchical Bayesian approach for exploring homogeneity of response in large area data sets, through a multicomponent mixture model. The approach allows the reduction of uncertainties through both full pooling and partial pooling of stations across automatically chosen subsets of the data. We apply the model to study the trends in annual maximum daily stream flow at 68 gauges over Germany. The effects of changing the number of clusters and the parameters used for clustering are demonstrated. The results show that there are large, mainly upward trends in the gauges of the River Rhine Basin in Western Germany and along the main stream of the Danube River in the south, while there are also some small upward trends at gauges in Central and Northern Germany. Y1 - 2015 U6 - https://doi.org/10.1002/2015WR017117 SN - 0043-1397 SN - 1944-7973 VL - 51 IS - 8 SP - 6586 EP - 6601 PB - American Geophysical Union CY - Washington ER - TY - JOUR A1 - Steirou, Eva A1 - Gerlitz, Lars A1 - Apel, Heiko A1 - Sun, Xun A1 - Merz, Bruno T1 - Climate influences on flood probabilities across Europe JF - Hydrology and earth system sciences : HESS N2 - The link between streamflow extremes and climatology has been widely studied in recent decades. However, a study investigating the effect of large-scale circulation variations on the distribution of seasonal discharge extremes at the European level is missing. Here we fit a climate-informed generalized extreme value (GEV) distribution to about 600 streamflow records in Europe for each of the standard seasons, i.e., to winter, spring, summer and autumn maxima, and compare it with the classical GEV distribution with parameters invariant in time. The study adopts a Bayesian framework and covers the period 1950 to 2016. Five indices with proven influence on the European climate are examined independently as covariates, namely the North Atlantic Oscillation (NAO), the east Atlantic pattern (EA), the east Atlantic-western Russian pattern (EA/WR), the Scandinavia pattern (SCA) and the polar-Eurasian pattern (POL). It is found that for a high percentage of stations the climate-informed model is preferred to the classical model. Particularly for NAO during winter, a strong influence on streamflow extremes is detected for large parts of Europe (preferred to the classical GEV distribution for 46% of the stations). Climate-informed fits are characterized by spatial coherence and form patterns that resemble relations between the climate indices and seasonal precipitation, suggesting a prominent role of the considered circulation modes for flood generation. For certain regions, such as northwestern Scandinavia and the British Isles, yearly variations of the mean seasonal climate indices result in considerably different extreme value distributions and thus in highly different flood estimates for individual years that can also persist for longer time periods. Y1 - 2019 U6 - https://doi.org/10.5194/hess-23-1305-2019 SN - 1027-5606 SN - 1607-7938 VL - 23 IS - 3 SP - 1305 EP - 1322 PB - Copernicus CY - Göttingen ER - TY - JOUR A1 - Steirou, Eva A1 - Gerlitz, Lars A1 - Sun, Xun A1 - Apel, Heiko A1 - Agarwal, Ankit A1 - Totz, Sonja Juliana A1 - Merz, Bruno T1 - Towards seasonal forecasting of flood probabilities in Europe using climate and catchment information JF - Scientific reports N2 - We investigate whether the distribution of maximum seasonal streamflow is significantly affected by catchment or climate state of the season/month ahead. We fit the Generalized Extreme Value (GEV) distribution to extreme seasonal streamflow for around 600 stations across Europe by conditioning the GEV location and scale parameters on 14 indices, which represent the season-ahead climate or catchment state. The comparison of these climate-informed models with the classical GEV distribution, with time-constant parameters, suggests that there is a substantial potential for seasonal forecasting of flood probabilities. The potential varies between seasons and regions. Overall, the season-ahead catchment wetness shows the highest potential, although climate indices based on large-scale atmospheric circulation, sea surface temperature or sea ice concentration also show some skill for certain regions and seasons. Spatially coherent patterns and a substantial fraction of climate-informed models are promising signs towards early alerts to increase flood preparedness already a season ahead. Y1 - 2022 U6 - https://doi.org/10.1038/s41598-022-16633-1 SN - 2045-2322 VL - 12 IS - 1 PB - Nature portfolio CY - Berlin ER -