2019, Chandorkar, Yashoda, Castro Nava, Arturo, Schweizerhof, Sjören, Van Dongen, Marcel, Haraszti, Tamás, Köhler, Jens, Zhang, Hang, Windoffer, Reinhard, Mourran, Ahmed, Möller, Martin, De Laporte, Laura

Cells feel the forces exerted on them by the surrounding extracellular matrix (ECM) environment and respond to them. While many cell fate processes are dictated by these forces, which are highly synchronized in space and time, abnormal force transduction is implicated in the progression of many diseases (muscular dystrophy, cancer). However, material platforms that enable transient, cyclic forces in vitro to recreate an in vivo-like scenario remain a challenge. Here, we report a hydrogel system that rapidly beats (actuates) with spatio-temporal control using a near infra-red light trigger. Small, user-defined mechanical forces (~nN) are exerted on cells growing on the hydrogel surface at frequencies up to 10 Hz, revealing insights into the effect of actuation on cell migration and the kinetics of reversible nuclear translocation of the mechanosensor protein myocardin related transcription factor A, depending on the actuation amplitude, duration and frequency.

2022, Mohapatra, Saurav Ranjan, Rama, Elena, Melcher, Christoph, Call, Tobias, Al Enezy-Ulbrich, Miriam Aischa, Pich, Andrij, Apel, Christian, Kiessling, Fabian, Jockenhoevel, Stefan

Background: The production of tissue-engineered vascular graft (TEVG) usually involves a prolonged bioreactor cultivation period of up to several weeks to achieve maturation of extracellular matrix and sufficient mechanical strength. Therefore, we aimed to substantially shorten this conditioning time by combining a TEVG textile scaffold with a recently developed copolymer reinforced fibrin gel as a cell carrier. We further implemented our grafts with magnetic resonance imaging (MRI) contrast agents to allow the in-vitro monitoring of the TEVG’s remodeling process. Methods: Biodegradable polylactic-co-glycolic acid (PLGA) was electrospun onto a non-degradable polyvinylidene fluoride scaffold and molded along with copolymer-reinforced fibrin hydrogel and human arterial cells. Mechanical tests on the TEVGs were performed both instantly after molding and 4 days of bioreactor conditioning. The non-invasive in vitro monitoring of the PLGA degradation and the novel imaging of fluorinated thermoplastic polyurethane (19F-TPU) were performed using 7T MRI. Results: After 4 days of close loop bioreactor conditioning, 617 ± 85 mmHg of burst pressure was achieved, and advanced maturation of extracellular matrix (ECM) was observed by immunohistology, especially in regards to collagen and smooth muscle actin. The suture retention strength (2.24 ± 0.3 N) and axial tensile strength (2.45 ± 0.58 MPa) of the TEVGs achieved higher values than the native arteries used as control. The contrast agents labeling of the TEVGs allowed the monitorability of the PLGA degradation and enabled the visibility of the non-degradable textile component. Conclusion: Here, we present a concept for a novel textile-reinforced TEVG, which is successfully produced in 4 days of bioreactor conditioning, characterized by increased ECM maturation and sufficient mechanical strength. Additionally, the combination of our approach with non-invasive imaging provides further insights into TEVG’s clinical application.

2019, Huo, Shuaidong, Gong, Ningqiang, Jiang, Ying, Chen, Fei, Guo, Hongbo, Gan, Yaling, Wang, Zhisen, Herrmann, Andreas, Liang, Xing-Jie

The development of an efficient delivery system for enhanced and controlled gene interference–based therapeutics is still facing great challenges. Fortunately, the flourishing field of nanotechnology provides more effective strategies for nucleic acid delivery. Here, the triplex-forming oligonucleotide sequence and its complementary strand were used to mediate self-assembly of ultrasmall gold nanoparticles. The obtained sunflower-like nanostructures exhibited strong near-infrared (NIR) absorption and photothermal conversion ability. Upon NIR irradiation, the large-sized nanostructure could disassemble and generate ultrasmall nanoparticles modified with c-myc oncogene silencing sequence, which could directly target the cell nucleus. Moreover, the controlled gene silencing effect could be realized by synergistically controlling the preincubation time with the self-assembled nanostructure (in vitro and in vivo) and NIR irradiation time point. This study provides a new approach for constructing more efficient and tailorable nanocarriers for gene interference applications

2023, Hosseinnejad, Aisa, Ludwig, Nadine, Mersmann, Sina, Winnerbach, Patrick, Bleilevens, Christian, Rossaint, Rolf, Rossaint, Jan, Singh, Smriti

Nitric oxide (NO) plays a significant role in controlling the physiology and pathophysiology of the body, including the endothelial antiplatelet function and therefore, antithrombogenic property of the blood vessels. This property of NO can be exploited to prevent thrombus formation on artificial surfaces like extracorporeal membrane oxygenators, which when come into contact with blood lead to protein adsorption and thereby platelet activation causing thrombus formation. However, NO is extremely reactive and has a very short biological half-life in blood, so only endogenous generation of NO from the blood contacting material can result into a stable and kinetically controllable local delivery of NO. In this regards, highly hydrophilic bioactive nanogels are presented which can endogenously generate NO in blood plasma from endogenous NO-donors thereby maintaining a physiological NO flux. It is shown that NO releasing nanogels could initiate cGMP-dependent protein kinase signaling followed by phosphorylation of vasodilator-stimulated phosphoprotein in platelets. This prevents platelet activation and aggregation even in presence of highly potent platelet activators like thrombin, adenosine 5′-diphosphate, and U46619 (thromboxane A2 mimetic).