@misc{SchoeneRochSchulzetal.2017,
  author    = {Sch{\"o}ne, Anne-Christin and Roch, Toralf and Schulz, Burkhard and Lendlein, Andreas},
  title     = {Evaluating polymeric biomaterial-environment interfaces by Langmuir monolayer techniques},
  series = {Interface : journal of the Royal Society},
  volume    = {14},
  journal   = {Interface : journal of the Royal Society},
  publisher = {Royal Society},
  address   = {London},
  issn      = {1742-5689},
  doi       = {10.1098/rsif.2016.1028},
  pages     = {18},
  year      = {2017},
  abstract  = {Polymeric biomaterials are of specific relevance in medical and pharmaceutical applications due to their wide range of tailorable properties and functionalities. The knowledge about interactions of biomaterials with their biological environment is of crucial importance for developing highly sophisticated medical devices. To achieve optimal in vivo performance, a description at the molecular level is required to gain better understanding about the surface of synthetic materials for tailoring their properties. This is still challenging and requires the comprehensive characterization of morphological structures, polymer chain arrangements and degradation behaviour. The review discusses selected aspects for evaluating polymeric biomaterial-environment interfaces by Langmuir monolayer methods as powerful techniques for studying interfacial properties, such as morphological and degradation processes. The combination of spectroscopic, microscopic and scattering methods with the Langmuir techniques adapted to polymers can substantially improve the understanding of their in vivo behaviour.},
  language  = {en}
}
@article{BhuvaneshSaretiaRochetal.2017,
  author    = {Bhuvanesh, Thanga and Saretia, Shivam and Roch, Toralf and Sch{\"o}ne, Anne-Christin and Rottke, Falko O. and Kratz, Karl and Wang, Weiwei and Ma, Nan and Schulz, Burkhard and Lendlein, Andreas},
  title     = {Langmuir-Schaefer films of fibronectin as designed biointerfaces for culturing stem cells},
  series = {Polymers for advanced technologies},
  volume    = {28},
  journal   = {Polymers for advanced technologies},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {1042-7147},
  doi       = {10.1002/pat.3910},
  pages     = {1305 -- 1311},
  year      = {2017},
  abstract  = {Glycoproteins adsorbing on an implant upon contact with body fluids can affect the biological response in vitro and in vivo, depending on the type and conformation of the adsorbed biomacromolecules. However, this process is poorly characterized and so far not controllable. Here, protein monolayers of high molecular cohesion with defined density are transferred onto polymeric substrates by the Langmuir-Schaefer (LS) technique and were compared with solution deposition (SO) method. It is hypothesized that on polydimethylsiloxane (PDMS), a substrate with poor cell adhesion capacity, the fibronectin (FN) layers generated by the LS and SO methods will differ in their organization, subsequently facilitating differential stem cell adhesion behavior. Indeed, atomic force microscopy visualization and immunofluorescence images indicated that organization of the FN layer immobilized on PDMS was uniform and homogeneous. In contrast, FN deposited by SO method was rather heterogeneous with appearance of structures resembling protein aggregates. Human mesenchymal stem cells showed reduced absolute numbers of adherent cells, and the vinculin expression seemed to be higher and more homogenously distributed after seeding on PDMS equipped with FN by LS in comparison with PDMS equipped with FN by SO. These divergent responses could be attributed to differences in the availability of adhesion molecule ligands such as the Arg-Gly-Asp (RGD) peptide sequence presented at the interface. The LS method allows to control the protein layer characteristics, including the thickness and the protein orientation or conformation, which can be harnessed to direct stem cell responses to defined outcomes, including migration and differentiation. Copyright (c) 2016 John Wiley \& Sons, Ltd.},
  language  = {en}
}
@misc{MoradianRochLendleinetal.2020,
  author    = {Moradian, Hanieh and Roch, Toralf and Lendlein, Andreas and Gossen, Manfred},
  title     = {mRNA transfection-induced activation of primary human monocytes and macrophages},
  series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {1},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-51569},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-515694},
  pages     = {17},
  year      = {2020},
  abstract  = {Monocytes and macrophages are key players in maintaining immune homeostasis. Identifying strategies to manipulate their functions via gene delivery is thus of great interest for immunological research and biomedical applications. We set out to establish conditions for mRNA transfection in hard-to-transfect primary human monocytes and monocyte-derived macrophages due to the great potential of gene expression from in vitro transcribed mRNA for modulating cell phenotypes. mRNA doses, nucleotide modifications, and different carriers were systematically explored in order to optimize high mRNA transfer rates while minimizing cell stress and immune activation. We selected three commercially available mRNA transfection reagents including liposome and polymer-based formulations, covering different application spectra. Our results demonstrate that liposomal reagents can particularly combine high gene transfer rates with only moderate immune cell activation. For the latter, use of specific nucleotide modifications proved essential. In addition to improving efficacy of gene transfer, our findings address discrete aspects of innate immune activation using cytokine and surface marker expression, as well as cell viability as key readouts to judge overall transfection efficiency. The impact of this study goes beyond optimizing transfection conditions for immune cells, by providing a framework for assessing new gene carrier systems for monocyte and macrophage, tailored to specific applications.},
  language  = {en}
}
@article{MoradianRochLendleinetal.2020,
  author    = {Moradian, Hanieh and Roch, Toralf and Lendlein, Andreas and Gossen, Manfred},
  title     = {mRNA transfection-induced activation of primary human monocytes and macrophages},
  series = {Scientific reports},
  volume    = {10},
  journal   = {Scientific reports},
  number    = {1},
  publisher = {Springer Nature},
  address   = {London},
  issn      = {2045-2322},
  doi       = {10.1038/s41598-020-60506-4},
  pages     = {1 -- 15},
  year      = {2020},
  abstract  = {Monocytes and macrophages are key players in maintaining immune homeostasis. Identifying strategies to manipulate their functions via gene delivery is thus of great interest for immunological research and biomedical applications. We set out to establish conditions for mRNA transfection in hard-to-transfect primary human monocytes and monocyte-derived macrophages due to the great potential of gene expression from in vitro transcribed mRNA for modulating cell phenotypes. mRNA doses, nucleotide modifications, and different carriers were systematically explored in order to optimize high mRNA transfer rates while minimizing cell stress and immune activation. We selected three commercially available mRNA transfection reagents including liposome and polymer-based formulations, covering different application spectra. Our results demonstrate that liposomal reagents can particularly combine high gene transfer rates with only moderate immune cell activation. For the latter, use of specific nucleotide modifications proved essential. In addition to improving efficacy of gene transfer, our findings address discrete aspects of innate immune activation using cytokine and surface marker expression, as well as cell viability as key readouts to judge overall transfection efficiency. The impact of this study goes beyond optimizing transfection conditions for immune cells, by providing a framework for assessing new gene carrier systems for monocyte and macrophage, tailored to specific applications.},
  language  = {en}
}
@article{NeffevonRuestenLangeBrauneetal.2014,
  author    = {Neffe, Axel T. and von R{\"u}sten-Lange, Maik and Braune, Steffen and L{\"u}tzow, Karola and Roch, Toralf and Richau, Klaus and Kr{\"u}ger, Anne and Becherer, Tobias and Th{\"u}nemann, Andreas F. and Jung, Friedrich and Haag, Rainer and Lendlein, Andreas},
  title     = {Multivalent grafting of hyperbranched oligo- and polyglycerols shielding rough membranes to mediate hemocompatibility},
  series = {Journal of materials chemistry : B, Materials for biology and medicine},
  volume    = {2},
  journal   = {Journal of materials chemistry : B, Materials for biology and medicine},
  number    = {23},
  publisher = {Royal Society of Chemistry},
  address   = {Cambridge},
  issn      = {2050-750X},
  doi       = {10.1039/c4tb00184b},
  pages     = {3626 -- 3635},
  year      = {2014},
  abstract  = {Hemocompatible materials are needed for internal and extracorporeal biomedical applications, which should be realizable by reducing protein and thrombocyte adhesion to such materials. Polyethers have been demonstrated to be highly efficient in this respect on smooth surfaces. Here, we investigate the grafting of oligo- and polyglycerols to rough poly(ether imide) membranes as a polymer relevant to biomedical applications and show the reduction of protein and thrombocyte adhesion as well as thrombocyte activation. It could be demonstrated that, by performing surface grafting with oligo-and polyglycerols of relatively high polydispersity (>1.5) and several reactive groups for surface anchoring, full surface shielding can be reached, which leads to reduced protein adsorption of albumin and fibrinogen. In addition, adherent thrombocytes were not activated. This could be clearly shown by immunostaining adherent proteins and analyzing the thrombocyte covered area. The presented work provides an important strategy for the development of application relevant hemocompatible 3D structured materials.},
  language  = {en}
}
@misc{NeffevonRuestenLangeBrauneetal.2014,
  author    = {Neffe, Axel T. and von R{\"u}sten-Lange, Maik and Braune, Steffen and L{\"u}tzow, Karola and Roch, Toralf and Richau, Klaus and Kr{\"u}ger, Anne and Becherer, Tobias and Th{\"u}nemann, Andreas F. and Jung, Friedrich and Haag, Rainer and Lendlein, Andreas},
  title     = {Multivalent grafting of hyperbranched oligo- and polyglycerols shielding rough membranes to mediate hemocompatibility},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-99444},
  year      = {2014},
  abstract  = {Hemocompatible materials are needed for internal and extracorporeal biomedical applications, which should be realizable by reducing protein and thrombocyte adhesion to such materials. Polyethers have been demonstrated to be highly efficient in this respect on smooth surfaces. Here, we investigate the grafting of oligo- and polyglycerols to rough poly(ether imide) membranes as a polymer relevant to biomedical applications and show the reduction of protein and thrombocyte adhesion as well as thrombocyte activation. It could be demonstrated that, by performing surface grafting with oligo- and polyglycerols of relatively high polydispersity (>1.5) and several reactive groups for surface anchoring, full surface shielding can be reached, which leads to reduced protein adsorption of albumin and fibrinogen. In addition, adherent thrombocytes were not activated. This could be clearly shown by immunostaining adherent proteins and analyzing the thrombocyte covered area. The presented work provides an important strategy for the development of application relevant hemocompatible 3D structured materials.},
  language  = {en}
}
@article{FriessRochSeifertetal.2019,
  author    = {Friess, Fabian and Roch, Toralf and Seifert, Barbara and Lendlein, Andreas and Wischke, Christian},
  title     = {Phagocytosis of spherical and ellipsoidal micronetwork colloids from crosslinked poly(epsilon-caprolactone)},
  series = {International Journal of Pharmaceutics},
  volume    = {567},
  journal   = {International Journal of Pharmaceutics},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {0378-5173},
  doi       = {10.1016/j.ijpharm.2019.118461},
  pages     = {7},
  year      = {2019},
  abstract  = {The effect of non-spherical particle shapes on cellular uptake has been reported as a general design parameter to control cellular recognition of particulate drug carriers. Beside shape, also size and cell-particle ratio should mutually effect phagocytosis. Here, the capability to control cellular uptake of poly(epsilon-caprolactone) (PCL) based polymer micronetwork colloids (MNC), a carrier system that can be transferred to various shapes, is explored in vitro at test conditions allowing multiple cell-particle contacts. PCL-based MNC were synthesized as spheres with a diameter of similar to 6, similar to 10, and 13 mu m, loaded with a fluorescent dye by a specific technique of swelling, redispersion and drying, and transferred into different ellipsoidal shapes by a phantom stretching method. The boundaries of MNC deformability to prolate ellipsoid target shapes were systematically analyzed and found to be at an aspect ratio AR of similar to 4 as obtained by a phantom elongation epsilon(ph) of similar to 150\%. Uptake studies with a murine macrophages cell line showed shape dependency of phagocytosis for selected conditions when varying particle sizes (similar to 6 and 10 mu m),and shapes (epsilon(ph): 0, 75 or 150\%), cell-particle ratios (1:1, 1:2, 1:10, 1:50), and time points (1-24 h). For larger-sized MNC, there was no significant shape effect on phagocytosis as these particles may associate with more than one cell, thus increasing the possibility of phagocytosis by any of these cells. Accordingly, controlling shape effects on phagocytosis for carriers made from degradable polymers relevant for medical applications requires considering further parameters besides shape, such as kinetic aspects of the exposure and uptake by cells.},
  language  = {en}
}
@article{NeffevonRuestenLangeBrauneetal.2013,
  author    = {Neffe, Axel T. and von R{\"u}sten-Lange, Maik and Braune, Steffen and L{\"u}tzow, Karola and Roch, Toralf and Richau, Klaus and Jung, Friedrich and Lendlein, Andreas},
  title     = {Poly(ethylene glycol) grafting to Poly(ether imide) membranes - influence on protein adsorption and Thrombocyte adhesion},
  series = {Macromolecular bioscience},
  volume    = {13},
  journal   = {Macromolecular bioscience},
  number    = {12},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {1616-5187},
  doi       = {10.1002/mabi.201300309},
  pages     = {1720 -- 1729},
  year      = {2013},
  abstract  = {The chain length and end groups of linear PEG grafted on smooth surfaces is known to influence protein adsorption and thrombocyte adhesion. Here, it is explored whether established structure function relationships can be transferred to application relevant, rough surfaces. Functionalization of poly(ether imide) (PEI) membranes by grafting with monoamino PEG of different chain lengths (M-n=1kDa or 10kDa) and end groups (methoxy or hydroxyl) is proven by spectroscopy, changes of surface hydrophilicity, and surface shielding effects. The surface functionalization does lead to reduction of adsorption of BSA, but not of fibrinogen. The thrombocyte adhesion is increased compared to untreated PEI surfaces. Conclusively, rough instead of smooth polymer or gold surfaces should be investigated as relevant models.},
  language  = {en}
}
@article{RochKratzMaetal.2015,
  author    = {Roch, Toralf and Kratz, Karl and Ma, Nan and Lendlein, Andreas},
  title     = {Polymeric inserts differing in their chemical composition as substrates for dendritic cell cultivation},
  series = {Clinical hemorheology and microcirculation : blood flow and vessels},
  volume    = {61},
  journal   = {Clinical hemorheology and microcirculation : blood flow and vessels},
  number    = {2},
  publisher = {IOS Press},
  address   = {Amsterdam},
  issn      = {1386-0291},
  doi       = {10.3233/CH-152004},
  pages     = {347 -- 357},
  year      = {2015},
  abstract  = {Dendritic cells (DC) contribute to immunity by presenting antigens to T cells and shape the immune response by the secretion of cytokines. Due to their immune stimulatory potential DC-based therapies are promising approaches to overcome tolerance e.g. against tumors. In order to enforce the immunogenicity of DCs, they have to be matured and activated in vitro, which requires an appropriate cell culture substrate, supporting their survival expansion and activation. Since most cell culture devices are not optimized for DC growth, it is hypothesized that polymers with certain physicochemical properties can positively influence the DC cultures. With the aim to evaluate the effects that polymers with different chemical compositions have on the survival, the activation status, and the cytokine/chemokine secretion profile of DC, their interaction with polystyrene (PS), polycarbonate (PC), poly(ether imide) (PEI), and poly(styrene-co-acrylonitrile) (PSAN)-based cell culture inserts was investigated. By using this insert system, which fits exactly into 24 well cell culture plates, effects induced from the culture dish material can be excluded. The viability of untreated DC after incubation with the different inserts was not influenced by the different inserts, whereas LPS-activatedDCshowed an increased survival after cultivation on PC, PS, and PSAN compared to tissue culture polystyrene (TCP). The activation status of DC estimated by the expression of CD40, CD80, CD83, CD86 and HLA-DR expression was not altered by the different inserts in untreated DC but slightly reduced when LPS-activated DC were cultivated on PC, PS, PSAN, and PEI compared to TCP. For each polymeric cell culture insert a distinct cytokine profile could be observed. Since inserts with different chemical compositions of the inserts did not substantially alter the behavior of DC all insert systems could be considered as alternative substrate. The observed increased survival on some polymers, which showed in contrast to TCP a hydrophobic surface, could be beneficial for certain applications such as T cell expansion and activation.},
  language  = {en}
}
@article{BhaskarMaLendleinetal.2015,
  author    = {Bhaskar, Thanga Bhuvanesh Vijaya and Ma, Nan and Lendlein, Andreas and Roch, Toralf},
  title     = {The interaction of human macrophage subsets with silicone as a biomaterial},
  series = {Clinical hemorheology and microcirculation : blood flow and vessels},
  volume    = {61},
  journal   = {Clinical hemorheology and microcirculation : blood flow and vessels},
  number    = {2},
  publisher = {IOS Press},
  address   = {Amsterdam},
  issn      = {1386-0291},
  doi       = {10.3233/CH-151991},
  pages     = {119 -- 133},
  year      = {2015},
  abstract  = {Silicones are widely used as biomaterials for medical devices such as extracorporeal equipments. However, there is often conflicting evidence about their supposed cell-and histocompatibility. Macrophages could mediate silicone-induced adverse responses such as foreign body reaction and fibrous encapsulation. The polarization behaviour of macrophages could determine the clinical outcome after implantation of biomaterials. Induction of classically activated macrophages (CAM) may induce and support uncontrolled inflammatory responses and undesired material degradation. In contrast, polarization into alternatively activated macrophages (AAM) is assumed to support healing processes and implant integration. This study compared the interaction of non-polarized macrophages (M0), CAM, and AAM with commercially available tissue culture polystyrene (TCP) and a medical grade silicone-based biomaterial, regarding the secretion of inflammatory mediators such as cytokines and chemokines. Firstly, by using the Limulus amoebocyte lysate (LAL) test the silicone films were shown to be free of soluble endotoxins, which is the prerequisite to investigate their interaction with primary immune cells. Primary human monocyte-derived macrophages (M0) were polarized into CAM and AAM by addition of suitable differentiation factors. These macrophage subsets were incubated on the materials for 24 hours and their viability and cytokine secretion was assessed. In comparison to TCP, cell adhesion was lower on silicone after 24 hours for all three macrophage subsets. However, compared to TCP, silicone induced higher levels of certain inflammatory and chemotactic cytokines in M0, CAM, and AAM macrophage subsets. Conclusively, it was shown that silicone has the ability to induce a pro-inflammatory state to different magnitudes dependent on the macrophage subsets. This priming of the macrophage phenotype by silicone could explain the incidence of severe foreign body complications observed in vivo.},
  language  = {en}
}