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 - Xu, Xun A1 - Nie, Yan A1 - Wang, Weiwei A1 - Ullah, Imran A1 - Tung, Wing Tai A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Generation of 2.5D lung bud organoids from human induced pluripotent stem cells JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - Human induced pluripotent stem cells (hiPSCs) are a promising cell source to generate the patient-specific lung organoid given their superior differentiation potential. However, the current 3D cell culture approach is tedious and time-consuming with a low success rate and high batch-to-batch variability. Here, we explored the establishment of lung bud organoids by systematically adjusting the initial confluence levels and homogeneity of cell distribution. The efficiency of single cell seeding and clump seeding was compared. Instead of the traditional 3D culture, we established a 2.5D organoid culture to enable the direct monitoring of the internal structure via microscopy. It was found that the cell confluence and distribution prior to induction were two key parameters, which strongly affected hiPSC differentiation trajectories. Lung bud organoids with positive expression of NKX 2.1, in a single-cell seeding group with homogeneously distributed hiPSCs at 70% confluence (SC 70% hom) or a clump seeding group with heterogeneously distributed cells at 90% confluence (CL 90% het), can be observed as early as 9 days post induction. These results suggest that a successful lung bud organoid formation with single-cell seeding of hiPSCs requires a moderate confluence and homogeneous distribution of cells, while high confluence would be a prominent factor to promote the lung organoid formation when seeding hiPSCs as clumps. 2.5D organoids generated with defined culture conditions could become a simple, efficient, and valuable tool facilitating drug screening, disease modeling and personalized medicine. KW - lung organoid KW - human induced pluripotent stem cell KW - cell culture Y1 - 2021 U6 - https://doi.org/10.3233/CH-219111 SN - 1386-0291 SN - 1875-8622 VL - 79 IS - 1 SP - 217 EP - 230 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Zhou, Shuo A1 - Xu, Xun A1 - Ma, Nan A1 - Jung, Friedrich A1 - Lendlein, Andreas T1 - Influence of sterilization conditions on sulfate-functionalized polyGGE JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - Sulfated biomolecules are known to influence numerous biological processes in all living organisms. Particularly, they contribute to prevent and inhibit the hypercoagulation condition. The failure of polymeric implants and blood contacting devices is often related to hypercoagulation and microbial contamination. Here, bioactive sulfated biomacromolecules are mimicked by sulfation of poly(glycerol glycidyl ether) (polyGGE) films. Autoclaving, gamma-ray irradiation and ethylene oxide (EtO) gas sterilization techniques were applied to functionalized materials. The sulfate group density and hydrophilicity of sulfated polymers were decreased while chain mobility and thermal degradation were enhanced post autoclaving when compared to those after EtO sterilization. These results suggest that a quality control after sterilization is mandatory to ensure the amount and functionality of functionalized groups are retained. KW - Sulfated polymer KW - sulfation KW - sterilization KW - ethylene oxide Y1 - 2021 U6 - https://doi.org/10.3233/CH-211241 SN - 1386-0291 SN - 1875-8622 VL - 79 IS - 4 SP - 597 EP - 608 PB - IOS Press CY - Amsterdam 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 - Nie, Yan A1 - Wang, Weiwei A1 - Xu, Xun A1 - Ma, Nan A1 - Lendlein, Andreas T1 - The response of human induced pluripotent stem cells to cyclic temperature changes explored by BIO-AFM JF - MRS advances : a journal of the Materials Research Society (MRS) N2 - Human induced pluripotent stem cells (hiPSCs) are highly sensitive to extrinsic physical and biochemical signals from their extracellular microenvironments. In this study, we analyzed the effect of cyclic temperature changes on hiPSCs behaviors, especially by means of scanning force microscopy (BIO-AFM). The alternation in cellular mechanics, as well as the secretion and pattern of deposition of extracellular matrix (ECM) protein in hiPSCs were evaluated. The arrangement of the actin cytoskeleton changed with the variation of the temperature. The rearranged cytoskeleton architecture led to the subsequent changes in cell mechanics (Young's modulus of hiPSCs). With the exposure to the cyclic cold stimuli, an increase in the average surface roughness (Ra) and roughness mean square (RMS) was detected. This observation might be at least in part due to the upregulated secretion of Laminin alpha 5 during repeated temporary cooling. The expression of pluripotent markers, NANOG and SOX2, was not impaired in hiPSCs, when exposed to the cyclic cold stimuli for 24 h. Our findings provide an insight into the effect of temperature on the hiPSC behaviors, which may contribute to a better understanding of the application of locally controlled therapeutic hypothermia. Y1 - 2021 U6 - https://doi.org/10.1557/s43580-021-00110-4 SN - 2059-8521 VL - 6 IS - 31 SP - 745 EP - 749 PB - Springer CY - Cham ER - TY - JOUR A1 - Xu, Xun A1 - Nie, Yan A1 - Wang, Weiwei A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Periodic thermomechanical modulation of toll-like receptor expression and distribution in mesenchymal stromal cells JF - MRS communications / a publication of the Materials Research Society N2 - Toll-like receptor (TLR) can trigger an immune response against virus including SARS-CoV-2. TLR expression/distribution is varying in mesenchymal stromal cells (MSCs) depending on their culture environments. Here, to explore the effect of periodic thermomechanical cues on TLRs, thermally controlled shape-memory polymer sheets with programmable actuation capacity were created. The proportion of MSCs expressing SARS-CoV-2-associated TLRs was increased upon stimulation. The TLR4/7 colocalization was promoted and retained in the endoplasmic reticula. The TLR redistribution was driven by myosin-mediated F-actin assembly. These results highlight the potential of boosting the immunity for combating COVID-19 via thermomechanical preconditioning of MSCs. KW - Actuation KW - Antiviral KW - Biomaterial KW - COVID-19 KW - Shape memory Y1 - 2021 U6 - https://doi.org/10.1557/s43579-021-00049-5 SN - 2159-6867 VL - 11 IS - 4 SP - 425 EP - 431 PB - Springer CY - Berlin ER - TY - JOUR A1 - Deng, Zijun A1 - Wang, Weiwei A1 - Xu, Xun A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Polydopamine-based biofunctional substrate coating promotes mesenchymal stem cell migration JF - MRS advances : a journal of the Materials Research Society (MRS) N2 - Rapid migration of mesenchymal stem cells (MSCs) on device surfaces could support in vivo tissue integration and might facilitate in vitro organoid formation. Here, polydopamine (PDA) is explored as a biofunctional coating to effectively promote MSC motility. It is hypothesized that PDA stimulates fibronectin deposition and in this way enhances integrin-mediated migration capability. The random and directional cell migration was investigated by time-lapse microscopy and gap closure assay respectively, and analysed with softwares as computational tools. A higher amount of deposited fibronectin was observed on PDA substrate, compared to the non-coated substrate. The integrin beta 1 activation and focal adhesion kinase (FAK) phosphorylation at Y397 were enhanced on PDA substrate, but the F-actin cytoskeleton was not altered, suggesting MSC migration on PDA was regulated by integrin initiated FAK signalling. This study strengthens the biofunctionality of PDA coating for regulating stem cells and offering a way of facilitating tissue integration of devices. Y1 - 2021 U6 - https://doi.org/10.1557/s43580-021-00091-4 SN - 2059-8521 VL - 6 IS - 31 SP - 739 EP - 744 PB - Springer Nature Switzerland AG CY - Cham ER - TY - JOUR A1 - Deng, Zijun A1 - Wang, Weiwei A1 - Xu, Xun A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Modulation of mesenchymal stem cell migration using programmable polymer sheet actuators JF - MRS advances N2 - Recruitment of mesenchymal stem cells (MSCs) to damaged tissue is a crucial step to modulate tissue regeneration. Here, the migration of human adipose-derived stem cells (hADSCs) responding to thermal and mechanical stimuli was investigated using programmable shape-memory polymer actuator (SMPA) sheets. Changing the temperature repetitively between 10 and 37 degrees C, the SMPA sheets are capable of reversibly changing between two different pre-defined shapes like an artificial muscle. Compared to non-actuating sheets, the cells cultured on the programmed actuating sheets presented a higher migration velocity (0.32 +/- 0.1 vs. 0.57 +/- 0.2 mu m/min). These results could motivate the next scientific steps, for example, to investigate the MSCs pre-loaded in organoids towards their migration potential. Y1 - 2020 U6 - https://doi.org/10.1557/adv.2020.235 SN - 2059-8521 VL - 5 IS - 46-47 SP - 2381 EP - 2390 PB - Cambridge Univ. Press CY - New York 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 - 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 -