46683
2017
2017
eng
18
14
review
Royal Society
London
1
--
--
--
Evaluating polymeric biomaterial-environment interfaces by Langmuir monolayer techniques
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.
Interface : journal of the Royal Society
10.1098/rsif.2016.1028
1742-5689
1742-5662
wos:2017
20161028
WOS:000402534200005
Lendlein, A (reprint author), Univ Potsdam, Inst Chem, Karl Liebknecht Str 24-25, D-14476 Potsdam, Germany.; Lendlein, A (reprint author), Helmholtz Zentrum Geesthacht, Inst Biomat Sci, Kantstr 55, D-14513 Teltow, Germany.; Lendlein, A (reprint author), Helmholtz Zentrum Geesthacht, Berlin Brandenburg Ctr Regenerat Therapies BCRT, Kantstr 55, D-14513 Teltow, Germany.; Lendlein, A (reprint author), Helmholtz Virtual Inst Multifunct Biomat Med, Kantstr 55, D-14513 Teltow, Germany., andreas.lendlein@hzg.de
Helmholtz Association [VH-VI-423]
importub
2020-04-20T03:31:01+00:00
filename=package.tar
2921def7437c0e73a270df3e7cd6b16a
Anne-Christin Schöne
Toralf Roch
Burkhard Schulz
Andreas Lendlein
eng
uncontrolled
Langmuir monolayer
eng
uncontrolled
biodegradable polymers
eng
uncontrolled
air - water interface
eng
uncontrolled
protein Langmuir layers
Institut für Chemie
Referiert
Import
46325
2017
2017
eng
1305
1311
7
28
article
Wiley
Hoboken
1
--
--
--
Langmuir-Schaefer films of fibronectin as designed biointerfaces for culturing stem cells
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.
Polymers for advanced technologies
10.1002/pat.3910
1042-7147
1099-1581
wos:2017
WOS:000409329300016
Lendlein, A (reprint author), Helmholtz Zentrum Geesthacht, Inst Biomat Sci, Kantstr 55, D-14513 Teltow, Germany., andreas.lendlein@hzg.de
Federal Ministry of Education and Research, Germany [1315848B]; Helmholtz-Association [VH-VI-423]
importub
2020-04-20T00:32:02+00:00
filename=package.tar
9c0235ffa0d2aedcefa3cb8e927bd152
Thanga Bhuvanesh
Shivam Saretia
Toralf Roch
Anne-Christin Schöne
Falko O. Rottke
Karl Kratz
Weiwei Wang
Nan Ma
Burkhard Schulz
Andreas Lendlein
eng
uncontrolled
Langmuir-Schaefer method
eng
uncontrolled
protein adsorption
eng
uncontrolled
stem cell adhesion
eng
uncontrolled
cell culture
eng
uncontrolled
fibronectin
Institut für Biochemie und Biologie
Referiert
Import
51569
2020
2020
eng
17
1
postprint
1
2020-03-06
2020-03-06
--
mRNA transfection-induced activation of primary human monocytes and macrophages
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.
Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
Dependence on carrier system and nucleotide modifcation
10.25932/publishup-51569
urn:nbn:de:kobv:517-opus4-515694
1866-8372
online registration
publish
<a href="http://publishup.uni-potsdam.de/61351">Bibliographieeintrag der Originalveröffentlichung/Quelle</a>
Sci Rep 10, 4181 (2020). https://doi.org/10.1038/s41598-020-60506-4
Version of Record
false
true
CC-BY - Namensnennung 4.0 International
Hanieh Moradian
Toralf Roch
Andreas Lendlein
Manfred Gossen
Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
1403
eng
uncontrolled
sirna transfection
eng
uncontrolled
mediated delivery
eng
uncontrolled
gene delivery
eng
uncontrolled
efficient
eng
uncontrolled
immunogenicity
eng
uncontrolled
lipoplexes
eng
uncontrolled
cells
eng
uncontrolled
therapeutics
eng
uncontrolled
polarization
eng
uncontrolled
pathways
Biowissenschaften; Biologie
open_access
Institut für Biochemie und Biologie
Referiert
Green Open-Access
Universität Potsdam
https://publishup.uni-potsdam.de/files/51569/zmnr1403.pdf
61351
2020
2020
eng
1
15
15
1
10
article
Springer Nature
London
1
2020-03-06
2020-03-06
--
mRNA transfection-induced activation of primary human monocytes and macrophages
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.
Scientific reports
Dependence on carrier system and nucleotide modifcation
10.1038/s41598-020-60506-4
2045-2322
4181
Manfred Gossen
2615211-3
<a href="https://doi.org/10.25932/publishup-51569">Zweitveröffentlichung in der Schriftenreihe Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe ; 1403</a>
CC-BY - Namensnennung 4.0 International
Hanieh Moradian
Toralf Roch
Andreas Lendlein
Manfred Gossen
eng
uncontrolled
sirna transfection
eng
uncontrolled
mediated delivery
eng
uncontrolled
gene delivery
eng
uncontrolled
efficient
eng
uncontrolled
immunogenicity
eng
uncontrolled
lipoplexes
eng
uncontrolled
cells
eng
uncontrolled
therapeutics
eng
uncontrolled
polarization
eng
uncontrolled
pathways
Biowissenschaften; Biologie
Institut für Biochemie und Biologie
Referiert
Gold Open-Access
DOAJ gelistet
38277
2014
2014
eng
3626
3635
10
23
2
article
Royal Society of Chemistry
Cambridge
1
--
--
--
Multivalent grafting of hyperbranched oligo- and polyglycerols shielding rough membranes to mediate hemocompatibility
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.
Journal of materials chemistry : B, Materials for biology and medicine
10.1039/c4tb00184b
2050-750X
2050-7518
wos:2014
WOS:000336851600008
Neffe, AT (reprint author), Helmholtz Zentrum Geesthacht, Inst Biomat Sci, Kantstr 55, D-14513 Teltow, Germany., axel.neffe@hzg.de; andreas.lendlein@hzg.de
Federal Ministry of Education and Research (BMBF) [1315696]
Axel T. Neffe
Maik von Rüsten-Lange
Steffen Braune
Karola Lützow
Toralf Roch
Klaus Richau
Anne Krüger
Tobias Becherer
Andreas F. Thünemann
Friedrich Jung
Rainer Haag
Andreas Lendlein
Institut für Chemie
Referiert
9944
2014
2014
eng
postprint
1
--
2014-03-27
--
Multivalent grafting of hyperbranched oligo- and polyglycerols shielding rough membranes to mediate hemocompatibility
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.
urn:nbn:de:kobv:517-opus4-99444
online registration
J. Mater. Chem. B (2014) Nr. 2, S. 3626-3635. - DOI: 10.1039/c4tb00184b
Axel T. Neffe
Maik von Rüsten-Lange
Steffen Braune
Karola Lützow
Toralf Roch
Klaus Richau
Anne Krüger
Tobias Becherer
Andreas F. Thünemann
Friedrich Jung
Rainer Haag
Andreas Lendlein
Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
285
Chemie und zugeordnete Wissenschaften
open_access
Institut für Chemie
Referiert
Open Access
Universität Potsdam
https://publishup.uni-potsdam.de/files/9944/pmnr285_online.pdf
48478
2019
2019
eng
7
567
article
Elsevier
Amsterdam
1
2019-06-24
--
--
Phagocytosis of spherical and ellipsoidal micronetwork colloids from crosslinked poly(epsilon-caprolactone)
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.
International Journal of Pharmaceutics
10.1016/j.ijpharm.2019.118461
31247276
0378-5173
1873-3476
wos:2019
118461
WOS:000477700500027
Wischke, C (reprint author), Helmholtz Zentrum Geesthacht, Inst Biomat Sci, D-14153 Teltow, Germany.; Wischke, C (reprint author), Helmholtz Zentrum Geesthacht, Berlin Brandenburg Ctr Regenerat Therapies, D-14153 Teltow, Germany., christian.wischke@hzg.de
Helmholtz-AssociationHelmholtz Association
2020-11-30T18:35:50+00:00
sword
importub
filename=package.tar
2bc0588a6956ab7ea3cab03df395d71d
false
true
Fabian Friess
Toralf Roch
Barbara Seifert
Andreas Lendlein
Christian Wischke
eng
uncontrolled
Particle shape
eng
uncontrolled
Phagocytosis
eng
uncontrolled
Macrophage
eng
uncontrolled
Polymer micronetwork colloids
eng
uncontrolled
Poly(epsilon-caprolactone)
Chemie und zugeordnete Wissenschaften
Institut für Chemie
Referiert
Import
34536
2013
2013
eng
1720
1729
10
12
13
article
Wiley-VCH
Weinheim
1
--
--
--
Poly(ethylene glycol) grafting to Poly(ether imide) membranes - influence on protein adsorption and Thrombocyte adhesion
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.
Macromolecular bioscience
10.1002/mabi.201300309
1616-5187
1616-5195
wos:2011-2013
WOS:000329994400010
Lendlein, A (reprint author), Helmholtz Zentrum Geesthacht, Inst Biomat Sci, Kantstr 55, D-14513 Teltow, Germany., andreas.lendlein@hzg.de
Bundesministerium fur Bildung und Forschung (BMBF) [0315696A]
Axel T. Neffe
Maik von Rüsten-Lange
Steffen Braune
Karola Lützow
Toralf Roch
Klaus Richau
Friedrich Jung
Andreas Lendlein
eng
uncontrolled
biomaterials
eng
uncontrolled
poly(ethylene glycol)
eng
uncontrolled
protein adsorption
eng
uncontrolled
surface functionalization
eng
uncontrolled
thrombocyte adhesion
Institut für Chemie
Referiert
39287
2015
2015
eng
347
357
11
2
61
article
IOS Press
Amsterdam
1
--
--
--
Polymeric inserts differing in their chemical composition as substrates for dendritic cell cultivation
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.
Clinical hemorheology and microcirculation : blood flow and vessels
10.3233/CH-152004
26444616
1386-0291
1875-8622
wos:2015
WOS:000364596000021
Roch, T (reprint author), Helmholtz Zentrum Geesthacht, Inst Biomat Sci, Kantstr 55, D-14513 Teltow, Germany., toralf.roch@hzg.de
German Federal Ministry of Education and Research [1315848B];
Helmholtz-Association [VH-VI-423, SO-036]
Toralf Roch
Karl Kratz
Nan Ma
Andreas Lendlein
eng
uncontrolled
Biomaterials
eng
uncontrolled
dendritic cells
eng
uncontrolled
cell culture device
eng
uncontrolled
amorphous polymers
Institut für Chemie
Referiert
39285
2015
2015
eng
119
133
15
2
61
article
IOS Press
Amsterdam
1
--
--
--
The interaction of human macrophage subsets with silicone as a biomaterial
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.
Clinical hemorheology and microcirculation : blood flow and vessels
10.3233/CH-151991
1386-0291
1875-8622
wos:2015
WOS:000364596000002
Roch, T (reprint author), Helmholtz Zentrum Geesthacht, Inst Biomat Sci, Kantstr 55, D-14513 Teltow, Germany., toralf.roch@hzg.de
Helmholtz Virtual Institute, Multifunctional Biomaterials for Medicine
[VH-VI-423]; Helmholtz-Association, Impuls- und Vernetzungsfond [SO-036]
Thanga Bhuvanesh Vijaya Bhaskar
Nan Ma
Andreas Lendlein
Toralf Roch
eng
uncontrolled
Biomaterials
eng
uncontrolled
silicone
eng
uncontrolled
macrophage subsets
eng
uncontrolled
cytokines/chemokines
Institut für Biochemie und Biologie
Referiert