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- ItemSperm Micromotors for Cargo Delivery through Flowing Blood(Washington, DC : American Chemical Society, 2020) Xu, Haifeng; Medina-Sánchez, Mariana; Maitz, Manfred F.; Werner, Carsten; Schmidt, Oliver G.Micromotors are recognized as promising candidates for untethered micromanipulation and targeted cargo delivery in complex biological environments. However, their feasibility in the circulatory system has been limited due to the low thrust force exhibited by many of the reported synthetic micromotors, which is not sufficient to overcome the high flow and complex composition of blood. Here we present a hybrid sperm micromotor that can actively swim against flowing blood (continuous and pulsatile) and perform the function of heparin cargo delivery. In this biohybrid system, the sperm flagellum provides a high propulsion force while the synthetic microstructure serves for magnetic guidance and cargo transport. Moreover, single sperm micromotors can assemble into a train-like carrier after magnetization, allowing the transport of multiple sperm or medical cargoes to the area of interest, serving as potential anticoagulant agents to treat blood clots or other diseases in the circulatory system.
- ItemPoly(2-alkyl-2-oxazoline)-Heparin Hydrogels—Expanding the Physicochemical Parameter Space of Biohybrid Materials(Weinheim : Wiley-VCH, 2021) Hahn, Dominik; Sonntag, Jannick M.; Lück, Steffen; Maitz, Manfred F.; Freudenberg, Uwe; Jordan, Rainer; Werner, CarstenPoly(ethylene glycol) (PEG)-glycosaminoglycan (GAG) hydrogel networks are established as very versatile biomaterials. Herein, the synthetic gel component of the biohybrid materials is systematically varied by combining different poly(2-alkyl-2-oxazolines) (POx) with heparin applying a Michael-type addition crosslinking scheme: POx of gradated hydrophilicity and temperature-responsiveness provides polymer networks of distinctly different stiffness and swelling. Adjusting the mechanical properties and the GAG concentration of the gels to similar values allows for modulating the release of GAG-binding growth factors (VEGF165 and PDGF-BB) by the choice of the POx and its temperature-dependent conformation. Adsorption of fibronectin, growth of fibroblasts, and bacterial adhesion scale with the hydrophobicity of the gel-incorporated POx. In vitro hemocompatibility tests with freshly drawn human whole blood show advantages of POx-based gels compared to the PEG-based reference materials. Biohybrid POx hydrogels can therefore enable biomedical technologies requiring GAG-based materials with customized and switchable physicochemical characteristics. © 2021 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.
- ItemThe innate immune response of self-assembling silk fibroin hydrogels(Cambridge : Royal Soc. of Chemistry, 2021) Gorenkova, Natalia; Maitz, Manfred F.; Böhme, Georg; Alhadrami, Hani A.; Jiffri, Essam H.; Totten, John D.; Werner, Carsten; Carswell, Hilary V. O.; Seib, F. PhilippSilk has a long track record of use in humans, and recent advances in silk fibroin processing have opened up new material formats. However, these new formats and their applications have subsequently created a need to ascertain their biocompatibility. Therefore, the present aim was to quantify the haemocompatibility and inflammatory response of silk fibroin hydrogels. This work demonstrated that self-assembled silk fibroin hydrogels, as one of the most clinically relevant new formats, induced very low blood coagulation and platelet activation but elevated the inflammatory response of human whole blood in vitro. In vivo bioluminescence imaging of neutrophils and macrophages showed an acute, but mild, local inflammatory response which was lower than or similar to that induced by polyethylene glycol, a benchmark material. The time-dependent local immune response in vivo was corroborated by histology, immunofluorescence and murine whole blood analyses. Overall, this study confirms that silk fibroin hydrogels induce a similar immune response to that of PEG hydrogels, while also demonstrating the power of non-invasive bioluminescence imaging for monitoring tissue responses. This journal is
- ItemA modular in vitro flow model to analyse blood-surface interactions under physiological conditions(Berlin : De Gruyter, 2021) Valtin, Juliane; Behrens, Stephan; Maitz, Manfred F.; Schmieder, Florian; Sonntag, Frank; Werner, CarstenNewly developed materials for blood-contacting devices need to undergo hemocompatibility testing to prove compliance with clinical requirements. However, many current in vitro models disregard the influence of flow conditions and blood exchange as it occurs in vivo. Here, we present a flow model which allows testing of blood-surface interactions under more physiological conditions. This modular platform consists of a triple-pump-chip and a microchannel-chip with a customizable surface. Flow conditions can be adjusted individually within the physiological range. A performance test with whole blood confirmed the hemocompatibility of our modular platform. Hemolysis was negligible, inflammation and hemostasis parameters were comparable to those detected in a previously established quasi-static whole blood screening chamber. The steady supply of fresh blood avoids secondary effects by nonphysiological accumulation of activation products. Experiments with three subsequently tested biomaterials showed results similar to literature and our own experience. The reported results suggest that our developed flow model allows the evaluation of blood-contacting materials under physiological flow conditions. By adjusting the occurring wall shear stress, the model can be adapted for selected test conditions.
- ItemBiocompatibility assessment of silk nanoparticles: hemocompatibility and internalization by human blood cells(New York, NY : Elsevier, 2017) Maitz, Manfred F.; Sperling, Claudia; Wongpinyochit, Thidarat; Herklotz, Manuela; Werner, Carsten; Seib, F. PhilippMany nanoparticles are designed for use as potential nanomedicines for parenteral administration. However, emerging evidence suggests that hemocompatibility is important, but is highly particle- and test-bed dependent. Thus, knowledge of bulk material properties does not predict the hemocompatibility of uncharacterized nanoparticles, including silk nanoparticles. This study compares the hemocompatibility of silk versus silica nanoparticles, using whole human blood under quasi-static and flow conditions. Substantial hemocompatibility differences are noted for some nanoparticles in quasi-static versus dynamic studies; i.e., the inflammatory response to silk nanoparticles is significantly lower under flow versus quasi-static conditions. Silk nanoparticles also have very low coagulant properties - an observation that scales from the macro- to the nano-level. These nanoparticle hemocompatibility studies are complemented by preliminary live cell measurements to evaluate the endocytosis and trafficking of nanoparticles in human blood cells. Overall, this study demonstrates that nanoparticle hemocompatibility is affected by several factors, including the test bed design.
- ItemReal-Time Monitoring of Blood Parameters in the Intensive Care Unit: State-of-the-Art and Perspectives(Basel : MDPI, 2022) Bockholt, Rebecca; Paschke, Shaleen; Heubner, Lars; Ibarlucea, Bergoi; Laupp, Alexander; Janićijević, Željko; Klinghammer, Stephanie; Balakin, Sascha; Maitz, Manfred F.; Werner, Carsten; Cuniberti, Gianaurelio; Baraban, Larysa; Spieth, Peter MarkusThe number of patients in intensive care units has increased over the past years. Critically ill patients are treated with a real time support of the instruments that offer monitoring of relevant blood parameters. These parameters include blood gases, lactate, and glucose, as well as pH and tem-perature. Considering the COVID-19 pandemic, continuous management of dynamic deteriorating parameters in patients is more relevant than ever before. This narrative review aims to summarize the currently available literature regarding real-time monitoring of blood parameters in intensive care. Both, invasive and non-invasive methods are described in detail and discussed in terms of general advantages and disadvantages particularly in context of their use in different medical fields but especially in critical care. The objective is to explicate both, well-known and frequently used as well as relatively unknown devices. Furtehrmore, potential future direction in research and development of realtime sensor systems are discussed. Therefore, the discussion section provides a brief description of current developments in biosensing with special emphasis on their technical implementation. In connection with these developments, the authors focus on different electrochemical approaches to invasive and non-invasive measurements in vivo.
- ItemDiscovery of hemocompatible bacterial biofilm-resistant copolymers(Amsterdam [u.a.] : Elsevier Science, 2020) Singh, Taranjit; Hook, Andrew L.; Luckett, Jeni; Maitz, Manfred F.; Sperling, Claudia; Werner, Carsten; Davies, Martyn C.; Irvine, Derek J.; Williams, Paul; Alexander, R.Blood-contacting medical devices play an important role within healthcare and are required to be biocompatible, hemocompatible and resistant to microbial colonization. Here we describe a high throughput screen for copolymers with these specific properties. A series of weakly amphiphilic monomers are combinatorially polymerized with acrylate glycol monomers of varying chain lengths to create a library of 645 multi-functional candidate materials containing multiple chemical moieties that impart anti-biofilm, hemo- and immuno-compatible properties. These materials are screened in over 15,000 individual biological assays, targeting two bacterial species, one Gram negative (Pseudomonas aeruginosa) and one Gram positive (Staphylococcus aureus) commonly associated with central venous catheter infections, using 5 different measures of hemocompatibility and 6 measures of immunocompatibililty. Selected copolymers reduce platelet activation, platelet loss and leukocyte activation compared with the standard comparator PTFE as well as reducing bacterial biofilm formation in vitro by more than 82% compared with silicone. Poly(isobornyl acrylate-co-triethylene glycol methacrylate) (75:25) is identified as the optimal material across all these measures reducing P. aeruginosa biofilm formation by up to 86% in vivo in a murine foreign body infection model compared with uncoated silicone. © 2020 The Authors