Towards a biocompatible artificial lung: Covalent functionalization of poly(4-methylpent-1-ene) (TPX) with <i>c</i>RGD pentapeptide

Möller, Lena; Heß, Christian; Paleček, J.; Su, Yi; Haverich, Axel; Kirschning, Andreas; Dräger, Gerald

doi:10.3762/bjoc.9.33

Cited by 17 publications

(14 citation statements)

References 32 publications

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“…34 For the design of a biohybrid lung, PDMS has excellent gas permeability and hemocompatibility and is amenable to various surface modifications. 1,2,12,16,17,36 We found that ECs in dynamic culture were proliferative and reached confluence on PDMS membranes within 3 days, as confirmed by immunocytochemistry (Fig. 2f).…”

Section: Discussionsupporting

confidence: 61%

EndOxy: Dynamic Long-Term Evaluation of Endothelialized Gas Exchange Membranes for a Biohybrid Lung

et al. 2019

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In the concept of a biohybrid lung, endothelial cells seeded on gas exchange membranes form a nonthrombogenic an anti-inflammatory surface to overcome the lacking hemocompatibility of today's oxygenators during extracorporeal membrane oxygenation. To evaluate this concept, the long-term stability and gas exchange performance of endothelialized RGD-conjugated polydimethylsiloxane (RGD-PDMS) membranes was evaluated. Human umbilical vein endothelial cells (ECs) were cultured on RGD-PDMS in a model system under physiological wall shear stress (WSS) of 0.5 Pa for up to 33 days. Gas exchange performance was tested with three biological replicates under elevated WSS of 2.5 Pa using porcine blood adjusted to venous values following ISO 7199 and blood gas analysis. EC morphology was assessed by immunocytochemistry (n = 3). RGD-PDMS promoted endothelialization and stability of endothelialized membranes was shown for at least 33 days and for a maximal WSS of 2.5 Pa. Short-term exposure to porcine blood did not affect EC integrity. The gas transfer tests provided evidence for the oxygenation and decarboxylation of the blood across endothelialized membranes with a decrease of transfer rates over time that needs to be addressed in further studies with larger sample sizes. Our results demonstrate the general suitability of RGD-PDMS for biohybrid lung applications, which might enable long-term support of patients with chronic lung failure in the future.

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Section: Discussionsupporting

confidence: 61%

EndOxy: Dynamic Long-Term Evaluation of Endothelialized Gas Exchange Membranes for a Biohybrid Lung

et al. 2019

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“…Perfluorophenyl azides form highly reactive nitrene intermediates under UV irradiation, and the latter readily undergo C─H insertion reactions with hydrocarbon‐based materials . Only a few studies report on using this methodology for surface functionalization of porous polymeric scaffolds, eg, melt‐blown poly(butylene terephthalate) (PBT) nonwoven fiber meshes or poly(4‐methyl‐1‐pentene) membranes . It was envisioned that the versatile PFPA chemistry can be used by inserting the perfluorophenyl nitrene intermediate into the aliphatic groups of PPDO.…”

Section: Introductionmentioning

confidence: 99%

“…17 Only a few studies report on using this methodology for surface functionalization of porous polymeric scaffolds, eg, meltblown poly(butylene terephthalate) (PBT) nonwoven fiber meshes 18 or poly(4-methyl-1-pentene) membranes. 19 It was envisioned that the versatile PFPA chemistry can be used by inserting the perfluorophenyl nitrene intermediate into the aliphatic groups of PPDO. As the reaction can be performed in a nonaqueous environment, it was hypothesized that polymer hydrolysis can be avoided with this strategy.…”

Section: Introductionmentioning

confidence: 99%

Perfluorophenyl azide functionalization of electrospun poly(para‐dioxanone)

Luetzow

Hommes-Schattmann

Neffe

et al. 2018

Polymers for Advanced Techs

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Strategies to surface‐functionalize scaffolds by covalent binding of biologically active compounds are of fundamental interest to control the interactions between scaffolds and biomolecules or cells. Poly(para‐dioxanone) (PPDO) is a clinically established polymer that has shown potential as temporary implant, eg, for the reconstruction of the inferior vena cava, as a nonwoven fiber mesh. However, PPDO lacks suitable chemical groups for covalent functionalization. Furthermore, PPDO is highly sensitive to hydrolysis, reflected by short in vivo half‐life times and degradation during storage. Establishing a method for covalent functionalization without degradation of this hydrolyzable polymer is therefore important to enable the surface tailoring for tissue engineering applications. It was hypothesized that treatment of PPDO with an N‐hydroxysuccinimide ester group bearing perfluorophenyl azide (PFPA) under UV irradiation would allow efficient surface functionalization of the scaffold. X‐ray photoelectron spectroscopy and attenuated total reflectance Fourier‐transformed infrared spectroscopy investigation revealed the successful binding, while a gel permeation chromatography study showed that degradation did not occur under these conditions. Coupling of a rhodamine dye to the N‐hydroxysuccinimide esters on the surface of a PFPA‐functionalized scaffold via its amine linker showed a homogenous staining of the PPDO in laser confocal microscopy. The PFPA method is therefore applicable even to the surface functionalization of hydrolytically labile polymers, and it was demonstrated that PFPA chemistry may serve as a versatile tool for the (bio‐)functionalization of PPDO scaffolds.

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“…Colonization with human endothelial progenitor cells on heparin/albumin-coated PMP membranes has also been shown. 30 Functionalization of the PMP surface by the covalent coupling of cell type-specific peptide sequences (e.g. cRGD, cyclic arginine-glycine asparagine) by means of copper-free "click" chemistry 30 or by coating with titanium oxide improved the adhesion of endothelial cells.…”

Section: Analysis and Design Of Biocompatible Membrane And System Surmentioning

confidence: 99%

Toward a Long-Term Artificial Lung

et al. 2020

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Only a very small portion of end-stage organ failures can be treated by transplantation because of the shortage of donor organs. Although artificial long-term organ support such as ventricular assist devices provide therapeutic options serving as a bridge-to-transplantation or destination therapy for endstage heart failure, suitable long-term artificial lung systems are still at an early stage of development. Although a shortterm use of an extracorporeal lung support is feasible today, the currently available technical solutions do not permit the long-term use of lung replacement systems in terms of an implantable artificial lung. This is currently limited by a variety of factors: biocompatibility problems lead to clot formation within the system, especially in areas with unphysiological flow conditions. In addition, proteins, cells, and fibrin are deposited on the membranes, decreasing gas exchange performance and thus, limiting long-term use. Coordinated basic and translational scientific research to solve these problems is therefore necessary to enable the long-term use and implantation of an artificial lung. Strategies for improving the biocompatibility of foreign surfaces, for new anticoagulation regimes, for optimization of gas and blood flow, and for miniaturization of these systems must be found. These strategies must be validated by in vitro and in vivo tests, which remain to be developed. In addition, the influence of long-term support on the pathophysiology must be considered. These challenges require well-connected interdisciplinary teams from the natural and material sciences, engineering, and medicine, which take the necessary steps toward the development of an artificial implantable lung. ASAIO Journal XXX; XX:00-00.

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Towards a biocompatible artificial lung: Covalent functionalization of poly(4-methylpent-1-ene) (TPX) with cRGD pentapeptide

Cited by 17 publications

References 32 publications

EndOxy: Dynamic Long-Term Evaluation of Endothelialized Gas Exchange Membranes for a Biohybrid Lung

EndOxy: Dynamic Long-Term Evaluation of Endothelialized Gas Exchange Membranes for a Biohybrid Lung

Perfluorophenyl azide functionalization of electrospun poly(para‐dioxanone)

Toward a Long-Term Artificial Lung

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