Developing a biohybrid lung – sufficient endothelialization of poly-4-methly-1-pentene gas exchange hollow-fiber membranes

Wiegmann, Bettina; Seggern, Heide von; Höffler, Klaus; Korossis, Sotirios; Dipresa, Daniele; Pflaum, Michael; Schmeckebier, Sabrina; Seume, Joerg R.; Haverich, Axel

doi:10.1016/j.jmbbm.2016.01.032

Cited by 30 publications

(46 citation statements)

References 30 publications

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“…Within our experimental setting, the HFM cell substrate and culture conditions might be equivalent to external influencing factors. Our qRT–PCR results indicate that neither the different seeding protocols nor the contact between the artificial surfaces and the endothelial cells had an impact on the physiological antithrombotic and anti‐inflammatory HCBEC activation status, verifying prior experiments (Wiegmann et al, ). Nevertheless, an application of prolonged and faster rotation during the seeding procedure decreased the relative expression levels of activation (ICAM‐1, VCAM‐1, and E‐selectin) and thrombogenic state (TF) markers.…”

Section: Discussionsupporting

confidence: 87%

“…As the native, quiescent endothelium inhibits cellular and plasmatic clotting alike, it appears to be the ideal blood–material interface, preserving blood flow not only by its passive characteristics but also due to active mechanisms (McGuigan & Sefton, ; Pearson, ). Generally, the endothelialization of synthetic materials is suitable for an improvement of artificial surface haemocompatibility (Achneck et al, ; Bos et al, ; Hess et al, ; Wiegmann et al, , ). Regarding the specific requirements of the BHL, however, additional aspects need to be considered to prepare for clinical application.…”

Section: Discussionmentioning

confidence: 99%

“…As shear exposure results in an adjustment of activation and thrombogenic state markers (Liu, Kluger, D'Alessio, García‐Cardeña, & Pober, ; Sampath, Kukielka, Smith, Eskin, & McIntire, ), the applied rotational seeding protocol may be responsible for the slight up‐regulations and down‐regulations of the relative expression levels we observed in unstimulated cells. They were significantly lower than the mRNA expression levels after TNFα stimulation but, nevertheless, responsible for higher initial expression values on PMP‐HFMs and resulted, in turn, in higher expression levels after TNFα stimulation (Wiegmann et al, ). However, all up‐regulated markers displayed significantly higher expression levels on H/A‐coated PMP than did those on uncoated PMP.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the approach to endothelialize artificial surfaces in order to improve their haemocompatibility and biocompatibility was also used in the development of a biohybrid lung (BHL) for long‐term application based on ECMO principles. Fundamental aspects, such as the general feasibility of endothelializing a heparin/albumin‐coated PMP surface and the identification of a suitable cell source for this approach, have already been investigated in previous work (Hess et al, ; Wiegmann et al, , ).…”

Section: Introductionmentioning

confidence: 99%

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Identifying an optimal seeding protocol and endothelial cell substrate for biohybrid lung development

Zwirner

Höffler

Pflaum

et al. 2018

J Tissue Eng Regen Med

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Several key prerequisites need to be fulfilled for the development of a biohybrid lung, which can offer an actual alternative to lung transplantation. A major aspect is an optimized haemocompatibility of the device's artificial surfaces via endothelial cell seeding. In this study, four different types of polymeric gas exchange hollow fibre membranes (HFMs) were analysed utilizing four different seeding protocols in order to identify the ideal combination for sufficient long-term endothelialization.Human cord blood-derived endothelial cells (HCBECs) were used for the endothelialization of polypropylene HFMs with two different pore sizes and poly-4-methyl-1pentene HFMs, both with and without heparin/albumin coating. The qualitative and quantitative impact of four different rotational seeding protocols regarding longterm HFM endothelialization and the impact of inflammatory stimulation on the seeded HCBECs were examined by fluorescence microscopy, cell counting, and analysis of relative expression levels of activation, shear stress, and thrombogenic state markers. Optimized endothelial cell seeding and long-term cultivation were only achieved using heparin/albumin-coated poly-4-methyl-1-pentene HFMs, applying 24 hr of rotational speed at 1 rpm followed by 120 hr of static culture. Neither cell-to-HFM contact nor the rotational cultivation procedure showed an impact on the physiological anti-thrombogenic and anti-inflammatory HCBEC activation status.Additionally, the cells maintained their physiological responsiveness towards inflammatory stimulation. Rotational seeding strategies and a seamless heparin/albumin coating of the HFMs are crucial requirements for a sufficient and long-lasting endothelialization and thus a key element in the future development and in vivo application of the biohybrid lung.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Identifying an optimal seeding protocol and endothelial cell substrate for biohybrid lung development

Zwirner

Höffler

Pflaum

et al. 2018

J Tissue Eng Regen Med

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“…This work is focused on the gas selective transport through PMP as well known membrane polymer. In spite of a long history of PMP investigation the scientific interest to this membrane material and the gas separating hollow fibers based on it are in the frames of active research now [29,30] and of the applications [31,32]. PMP is using up to now as the hollow fiber air separation membranes.…”

Section: Introductionmentioning

confidence: 99%

Diffusion of C1-C3 Alkanes in Semicrystalline Poly(4-Methyl-1- Pentene) as a Two-Phase Polymeric System

Teplyakov¹

2017

Int. J. Membrane Sci. Techno.

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Poly(4-methyl-1-pentene) (PMP) is using up to now as the hollow fiber air separation membranes. This polymer with good resistance to organics attack can be prospective for separation of lower hydrocarbons.An attempt for the theoretical consideration and experimental study of the C1-C3 alkanes diffusion in poly(4-methyl-1pentene) (PMP) as a binary system in the temperature range from 253,K to 353, K covering the glass transition region of PMP (~ 303, K) is carried out in this work. The permeability of CH4, C2H6, C3H8 has been measured by the permeability differential method under the partial pressure drop across the membrane 1 bar with the gas chromatography analysis of the permeate flux. The diffusion coefficients have been calculated from the experimental differential permeability curves by using linearization method developed earlier. Novelty of results is that at temperatures below Tg PMP can be considered as a single-phase system from the gas transfer point of view. At the temperatures above Tg PMP can be considered as a two-phase medium with diffusion coefficients of C1-C3 alkanes in amorphous (Da) and crystalline phases (Dc) (Da>Dc) which differ by not more than an one order of magnitude. For the first time it is shown that the diffusivity of C1-C3 alkanes in amorphous and crystalline PMP phases is decreasing in accordance with sequence DCH4 >DC2H6 >DC3H8. A certain scatter of the PMP data published in the literature was noted. Obtained data can be relatively compared with published ones only for methane: for virgin PMP films we obtained PCH4 = 16.7 Barrer; it is known for the extrusion PMP films that PCH4 = 14.6 -19.8 Barrer, for casted PMP films PCH4 = 0.4 -1.2 Barrer. The values for ethane and propane in crystalline phase of PMP are obtained for the first time. Evaluation of permeability through crystalline phase at temperature 313,K shows that PC2H6 = 15 Barrer; PC3H8 = 5 Barrer. For real estimation of the separation efficiency PMP it is needed an additional research with taking into account the crystallinity and temperature dependences for diffusivity based on results of this study.

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Membrane bioreactors for (bio-)artificial lung

Pflaum

Peredo

Dipresa

et al. 2020

Current Trends and Future Developments on (Bio-) Membranes

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Developing a biohybrid lung – sufficient endothelialization of poly-4-methly-1-pentene gas exchange hollow-fiber membranes

Cited by 30 publications

References 30 publications

Identifying an optimal seeding protocol and endothelial cell substrate for biohybrid lung development

Identifying an optimal seeding protocol and endothelial cell substrate for biohybrid lung development

Diffusion of C1-C3 Alkanes in Semicrystalline Poly(4-Methyl-1- Pentene) as a Two-Phase Polymeric System

Membrane bioreactors for (bio-)artificial lung

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