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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.
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.
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.
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.
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.
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.
Shear-induced platelet adherence and activation in an in-vitro dynamic multiwell-plate system
(2019)
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.
Spontaneous and induced platelet aggregation in apparently healthy subjects in relation to age
(2019)
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.
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.