TY  - JOUR
A1  - Lange, Maik
A1  - Braune, Steffen
A1  - Luetzow, Karola
A1  - Richau, Klaus
A1  - Scharnagl, Nico
A1  - Weinhart, Marie
A1  - Neffe, Axel T.
A1  - Jung, Friedrich
A1  - Haag, Rainer
A1  - Lendlein, Andreas
T1  - Surface functionalization of poly(ether imide) membranes with linear, methylated oligoglycerols for reducing thrombogenicity
JF  - Macromolecular rapid communications
N2  - Materials for biomedical applications are often chosen for their bulk properties. Other requirements such as a hemocompatible surface shall be fulfilled by suitable chemical functionalization. Here we show, that linear, side-chain methylated oligoglycerols (OGMe) are more stable to oxidation than oligo(ethylene glycol) (OEG). Poly(ether imide) (PEI) membranes functionalized with OGMes perform at least as good as, and partially better than, OEG functionalized PEI membranes in view of protein resistance as well as thrombocyte adhesion and activation. Therefore, OGMes are highly potent surface functionalizing molecules for improving the hemocompatibility of polymers.
KW  - hemocompatibility
KW  - poly(ethylene glycol)
KW  - polyglycerol
KW  - polyimides
KW  - surface chemistry
Y1  - 2012
U6  - https://doi.org/10.1002/marc.201200426
SN  - 1022-1336
VL  - 33
IS  - 17
SP  - 1487
EP  - 1492
PB  - Wiley-VCH
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Kuhnla, A.
A1  - Reinthaler, Markus
A1  - Braune, Steffen
A1  - Maier, A.
A1  - Pindur, Gerhard
A1  - Lendlein, Andreas
A1  - Jung, Friedrich
T1  - Spontaneous and induced platelet aggregation in apparently healthy subjects in relation to age
JF  - Clinical hemorheology and microcirculation : blood flow and vessels
N2  - Thrombotic disorders remain the leading cause of mortality and morbidity, despite the fact that anti-platelet therapies and vascular implants are successfully used today. As life expectancy is increasing in western societies, the specific knowledge about processes leading to thrombosis in elderly is essential for an adequate therapeutic management of platelet dysfunction and for tailoring blood contacting implants. This study addresses the limited available data on platelet function in apparently healthy subjects in relation to age, particularly in view of subjects of old age (80-98 years). Apparently healthy subjects between 20 and 98 years were included in this study. Platelet function was assessed by light transmission aggregometry and comprised experiments on spontaneous as well as ristocetin-, ADP- and collagen-induced platelet aggregation. The data of this study revealed a non-linear increase in the maximum spontaneous platelet aggregation (from 3.3% +/- 3.3% to 10.9% +/- 5.9%). The maximum induced aggregation decreased with age for ristocetin (from 85.8% +/- 7.2% to 75.0% +/- 7.8%), ADP (from 88.5% +/- 4.6% to 64.8% +/- 7.3%) and collagen (from 89.5% +/- 3.0% to 64.0% +/- 4.0%) in a non-linear manner (linear regression analysis). These observations indicate that during aging, circulating platelets become increasingly activated but lose their full aggregatory potential, a phenomenon that was earlier termed "platelet exhaustion". In this study we extended the limited existing data for spontaneous and induced platelet aggregation of apparently healthy donors above the age of 75 years. The presented data indicate that the extrapolation of data from a middle age group does not necessarily predict platelet function in apparently healthy subjects of old age. It emphasizes the need for respective studies to improve our understanding of thrombotic processes in elderly humans.
Y1  - 2019
U6  - https://doi.org/10.3233/CH-199006
SN  - 1386-0291
SN  - 1875-8622
VL  - 71
IS  - 4
SP  - 425
EP  - 435
PB  - IOS Press
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Reinthaler, Markus
A1  - Johansson, Johan Backemo
A1  - Braune, Steffen
A1  - Al-Hindwan, Haitham Saleh Ali
A1  - Lendlein, Andreas
A1  - Jung, Friedrich
T1  - Shear-induced platelet adherence and activation in an in-vitro dynamic multiwell-plate system
JF  - Clinical hemorheology and microcirculation : blood flow and vessels
N2  - Circulating blood cells are prone to varying flow conditions when contacting cardiovascular devices. For a profound understanding of the complex interplay between the blood components/cells and cardiovascular implant surfaces, testing under varying shear conditions is required. Here, we study the influence of arterial and venous shear conditions on the in vitro evaluation of the thrombogenicity of polymer-based implant materials. Medical grade poly(dimethyl siloxane) (PDMS), polyethylene terephthalate (PET) and polytetrafluoroethylene (PTFE) films were included as reference materials. The polymers were exposed to whole blood from healthy humans. Blood was agitated orbitally at low (venous shear stress: 2.8 dyne. cm(-2)) and high (arterial shear stress: 22.2 dyne .cm(-2)) agitation speeds in a well-plate based test system. Numbers of non-adherent platelets, platelet activation (P-Selectin positive platelets), platelet function (PFA100 closure times) and platelet adhesion (laser scanning microscopy (LSM)) were determined. Microscopic data and counting of the circulating cells revealed increasing numbers of material-surface adherent platelets with increasing agitation speed. Also, activation of the platelets was substantially increased when tested under the high shear conditions (P-Selectin levels, PFA-100 closure times). At low agitation speed, the platelet densities did not differ between the three materials. Tested at the high agitation speed, lowest platelet densities were observed on PDMS, intermediate levels on PET and highest on PTFE. While activation of the circulating platelets was affected by the implant surfaces in a similar manner, PFA closure times did not reflect this trend. Differences in the thrombogenicity of the studied polymers were more pronounced when tested at high agitation speed due to the induced shear stresses. Testing under varying shear stresses, thus, led to a different evaluation of the implant thrombogenicity, which emphasizes the need for testing under various flow conditions. Our data further confirmed earlier findings where the same reference implants were tested under static (and not dynamic) conditions and with fresh human platelet rich plasma instead of whole blood. This supports that the application of common reference materials may improve inter-study comparisons, even under varying test conditions.
Y1  - 2019
U6  - https://doi.org/10.3233/CH-189410
SN  - 1386-0291
SN  - 1875-8622
VL  - 71
IS  - 2
SP  - 183
EP  - 191
PB  - IOS Press
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Blocki, Anna
A1  - Löwenberg, Candy
A1  - Jiang, Yi
A1  - Kratz, Karl
A1  - Neffe, Axel T.
A1  - Jung, Friedrich
A1  - Lendlein, Andreas
T1  - Response of encapsulated cells to a gelatin matrix with varied bulk and microenvironmental elastic properties
JF  - Polymers for advanced technologies
N2  - Gelatin-based hydrogels offer various biochemical cues that support encapsulated cells and are therefore suitable as cell delivery vehicles in regenerative medicine. However, besides the biochemical signals, biomechanical cues are crucial to ensure an optimal support of encapsulated cells. Hence, we aimed to correlate the cellular response of encapsulated cells to macroscopic and microscopic elastic properties of glycidylmethacrylate (GMA)-functionalized gelatin-based hydrogels. To ensure that different observations in cellular behavior could be attributed to differences in elastic properties, an identical concentration as well as degree of functionalization of biopolymers was utilized to form covalently crosslinked hydrogels. Elastic properties were merely altered by varying the average gelatin-chain length. Hydrogels exhibited an increased degree of swelling and a decreased bulk elastic modulus G with prolonged autoclaving of the starting solution. This was accompanied by an increase of hydrogel mesh size and thus by a reduction of crosslinking density. Tougher hydrogels retained the largest amount of cells; however, they also interfered with cell viability. Softer gels contained a lower cell density, but supported cell elongation and viability. Observed differences could be partially attributed to differences in bulk properties, as high crosslinking densities interfere with diffusion and cell spreading and thus can impede cell viability. Interestingly, a microscopic elastic modulus in the range of native soft tissue supported cell viability and elongation best while ensuring a good cell entrapment. In conclusion, gelatin-based hydrogels providing a soft tissue-like microenvironment represent adequate cell delivery vehicles for tissue engineering approaches. Copyright (c) 2016 John Wiley & Sons, Ltd.
KW  - mechanotransduction
KW  - hydrogel
KW  - gelatin
KW  - cell encapsulation
KW  - matrix elasticity
Y1  - 2017
U6  - https://doi.org/10.1002/pat.3947
SN  - 1042-7147
SN  - 1099-1581
VL  - 28
SP  - 1245
EP  - 1251
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Neffe, Axel T.
A1  - von Rüsten-Lange, Maik
A1  - Braune, Steffen
A1  - Lützow, Karola
A1  - Roch, Toralf
A1  - Richau, Klaus
A1  - Jung, Friedrich
A1  - Lendlein, Andreas
T1  - Poly(ethylene glycol) grafting to Poly(ether imide) membranes - influence on protein adsorption and Thrombocyte adhesion
JF  - Macromolecular bioscience
N2  - 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.
KW  - biomaterials
KW  - poly(ethylene glycol)
KW  - protein adsorption
KW  - surface functionalization
KW  - thrombocyte adhesion
Y1  - 2013
U6  - https://doi.org/10.1002/mabi.201300309
SN  - 1616-5187
SN  - 1616-5195
VL  - 13
IS  - 12
SP  - 1720
EP  - 1729
PB  - Wiley-VCH
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Neffe, Axel T.
A1  - von Rüsten-Lange, Maik
A1  - Braune, Steffen
A1  - Lützow, Karola
A1  - Roch, Toralf
A1  - Richau, Klaus
A1  - Krüger, Anne
A1  - Becherer, Tobias
A1  - Thünemann, Andreas F.
A1  - Jung, Friedrich
A1  - Haag, Rainer
A1  - Lendlein, Andreas
T1  - Multivalent grafting of hyperbranched oligo- and polyglycerols shielding rough membranes to mediate hemocompatibility
JF  - Journal of materials chemistry : B, Materials for biology and medicine
N2  - 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.
Y1  - 2014
U6  - https://doi.org/10.1039/c4tb00184b
SN  - 2050-750X
SN  - 2050-7518
VL  - 2
IS  - 23
SP  - 3626
EP  - 3635
PB  - Royal Society of Chemistry
CY  - Cambridge
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  - Rüder, Constantin
A1  - Sauter, Tilman
A1  - Kratz, Karl
A1  - Haase, Tobias
A1  - Peter, Jan
A1  - Jung, Friedrich
A1  - Lendlein, Andreas
A1  - Zohlnhöfer, Dietlind
T1  - Influence of fibre diameter and orientation of electrospun copolyetheresterurethanes on smooth muscle and endothelial cell behaviour
JF  - Clinical hemorheology and microcirculation : blood flow and vessels
N2  - Polymers exhibiting cell-selective effects represent an extensive research field with high relevance for biomedical applications e.g. in the cardiovascular field supporting re-endothelialization while suppressing smooth muscle cell overgrowth. Such an endothelial cell-selective effect could be recently demonstrated for a copolyetheresterurethane (PDC) containing biodegradable poly(p-dioxanone) and poly(epsilon-caprolactone) segments, which selectively enhanced the adhesion of human umbilical vein endothelial cells (HUVEC) while suppressing the attachment of smooth muscle cells (SMC).
 In this study we investigated the influence of the fibre orientation (random and aligned) and fibre diameter (2 mu m and 500 nm) of electrospun PDC scaffolds on the adhesion, proliferation and apoptosis of HUVEC and SMC.
 Adhesion, viability and proliferation of HUVEC was diminished when the fibre diameter was reduced to a submicron scale, while the orientation of the microfibres did only slightly influence the cellular behaviour. In contrast, a submicron fibre diameter improved SMC viability. In conclusion, PDC scaffolds with micron-sized single fibres could be promising candidate materials for cell-selective stent coatings.
KW  - Endothelialization
KW  - drug eluting stent
KW  - degradable polymer
KW  - electrospinning
KW  - cell selectivity
Y1  - 2013
U6  - https://doi.org/10.3233/CH-131787
SN  - 1386-0291
SN  - 1875-8622
VL  - 55
IS  - 4
SP  - 513
EP  - 522
PB  - IOS Press
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Krüger-Genge, A.
A1  - Braune, S.
A1  - Walter, M.
A1  - Krengel, M.
A1  - Kratz, K.
A1  - Küpper, J. H.
A1  - Lendlein, Andreas
A1  - Jung, Friedrich
T1  - Influence of different surface treatments of poly(n-butyl acrylate) networks on fibroblasts adhesion, morphology and viability
JF  - Clinical hemorheology and microcirculation : blood flow and vessels
N2  - BACKGROUND: Physical and chemical characteristics of implant materials determine the fate of long-term cardiovascular devices. However, there is still a lack of fundamental understanding of the molecular mechanisms occurring in the material-tissue interphase. In a previous study, soft covalently crosslinked poly(n-butyl acrylate) networks (cPnBA) were introduced as sterilizable, non-toxic and immuno-compatible biomaterials with mechanical properties adjustable to blood vessels. Here we study the influence of different surface treatments in particular oxygen plasma modification and fibrinogen deposition as well as a combinatorial approach on the adhesion and viability of fibroblasts. RESULTS: Compared to non-treated cPnBAs the advancing water-contact angles were found to be reduced after all surface modifications (p<0.05, each), while lowest values were observed after the combined surface treatment (OPT+FIB). The latter differed significantly from the single OPT and FIB. The number of adherent fibroblasts and their adherence behavior differed on both pristine cPnBA networks. The fibroblast density on cPnBA04 was 743 +/- 434 cells. mm(-2), was about 6.5 times higher than on cPnBA73 with 115 +/- 73 cells. mm(-2). On cPnBA04 about 20% of the cells were visible as very small, round and buckled cells while all other cells were in a migrating status. On cPnBA73, nearly 50% of fibroblasts were visible as very small, round and buckled cells. The surface functionalization either using oxygen plasma treatment or fibrinogen coating led to a significant increase of adherent fibroblasts, particularly the combination of both techniques, for both cPnBA networks. It is noteworthy to mention that the fibrinogen coating overruled the characteristics of the pristine surfaces; here, the fibroblast densities after seeding were identical for both cPnBAnetworks. Thus, the binding rather depended on the fibrinogen coating than on the substrate characteristics anymore. While the integrity of the fibroblasts membrane was comparable for both polymers, the MTS tests showed a decreased metabolic activity of the fibroblasts on cPnBA. CONCLUSION: The applied surface treatments of cPnBA successfully improved the adhesion of viable fibroblasts. Under resting conditions as well as after shearing the highest fibroblast densities were found on surfaces with combined post-treatment.
KW  - Biomaterial
KW  - poly(n-butyl acrylate)
KW  - fibroblast
KW  - oxygen plasma
KW  - fibrinogen
KW  - cell adhesion
KW  - focal adhesion
KW  - actin cytoskeleton
KW  - viability
Y1  - 2018
U6  - https://doi.org/10.3233/CH-189130
SN  - 1386-0291
SN  - 1875-8622
VL  - 69
IS  - 1-2
SP  - 305
EP  - 316
PB  - IOS Press
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Haase, Tobias
A1  - Krost, Annalena
A1  - Sauter, Tilman
A1  - Kratz, Karl
A1  - Peter, Jan
A1  - Kamann, Stefanie
A1  - Jung, Friedrich
A1  - Lendlein, Andreas
A1  - Zohlnhöfer, Dietlind
A1  - Rüder, Constantin
T1  - In vivo biocompatibility assessment of poly (ether imide) electrospun scaffolds
JF  - Journal of Tissue Engineering and Regenerative Medicine
N2  - Poly(ether imide) (PEI), which can be chemically functionalized with biologically active ligands, has emerged as a potential biomaterial for medical implants. Electrospun PEI scaffolds have shown advantageous properties, such as enhanced endothelial cell adherence, proliferation and low platelet adhesion in in vitro experiments. In this study, the in vivo behaviour of electrospun PEI scaffolds and PEI films was examined in a murine subcutaneous implantation model. Electrospun PEI scaffolds and films were surgically implanted subcutaneously in the dorsae of mice. The surrounding subcutaneous tissue response was examined via histopathological examination at 7 and 28days after implantation. No serious adverse events were observed for both types of PEI implants. The presence of macrophages or foreign body giant cells in the vicinity of the implants and the formation of a fibrous capsule indicated a normal foreign body reaction towards PEI films and scaffolds. Capsule thickness and inflammatory infiltration cells significantly decreased for PEI scaffolds during days 7-28 while remaining unchanged for PEI films. The infiltration of cells into the implant was observed for PEI scaffolds 7days after implantation and remained stable until 28days of implantation. Additionally some, but not all, PEI scaffold implants induced the formation of functional blood vessels in the vicinity of the implants. Conclusively, this study demonstrates the in vivo biocompatibility of PEI implants, with favourable properties of electrospun PEI scaffolds regarding tissue integration and wound healing.
KW  - poly(ether imide)
KW  - in vivo study
KW  - electrospun scaffold
KW  - capsule formation
KW  - foreign body giant cells
KW  - vascularization
Y1  - 2017
U6  - https://doi.org/10.1002/term.2002
SN  - 1932-6254
SN  - 1932-7005
VL  - 11
IS  - 4
SP  - 1034
EP  - 1044
PB  - Wiley
CY  - Hoboken
ER  -