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Design of an anti-inflammatory coating for invasive medical devices
Design of an anti-inflammatory coating for invasive medical devices
The prevention of material-mediated innate immune responses, which may lead to severe side effects, is an unsolved issue in invasive medicine. Neutrophil granulocytes are activated upon contact of blood with artificial material surfaces in medical devices. This unappreciated non-specific immune response provides a challenge for invasive medicine, since it may cause systemic inflammatory reactions and severe sequelae such as organ failure or even death. This thesis investigates the design an anti-inflammatory surface coating, which avoids or reduces material-mediated innate immune responses on the example of the material polymethylpentene (PMP). PMP is a polymer, which is used as hollow fibers in medical devices like oxygenators enabling the exchange of oxygen and carbon dioxide in the blood. Therefore, a biofunctional anti-inflammatory coating has been developed to avoid material-mediated neutrophil activation during respiratory support. The biofunctional anti-inflammatory coating is based on the covalent coupling of the agonistic FasL-molecule APO010, the covalent coupling of albumin (Recombumin® alpha) to passivate the coating and an amino acid-based stabilizing formulation to enable stability and functionality of the coating even after ethylenoxid (EtO)-sterilization and subsequent storage of the device. To investigate the stability and functionality of the coating, different methods were established: an ELISA to investigate the stable coupling of the biofunctional coating, a sandwich ELISA to detect detached APO010 and a chemotaxis assay to investigate the reduction of neutrophil activity after incubation with the coating. The novel coating has been upscaled from laboratory scale (bench setting) to a serial production scale, whereby the methods from this work were able to show a rapid reduction of neutrophil activation by approx. 10 % after contacting the surface in the second serial production run and the stability of the surface coating even after accelerated aging for up to 82 days at 55 °C in the third serial production run. Three upscaling steps were performed to generate homogeneous distribution of the coating on the PMP matrix. The biofunctional anti-inflammatory coating is a new technology to reduce unappreciated material-induced immunogenic responses. In principle, it should be possible to transfer this technology to other surfaces. This could allow for expansion of the positive effects to other medical devices in direct blood contact and can possibly show the way for new biofunctional coatings in the medical device sector.
Neutrophils, biofunctionalized polymethylpentene, inflammation, FasL, coating
Reinauer, Eva
2018
English
Universitätsbibliothek der Ludwig-Maximilians-Universität München
Reinauer, Eva (2018): Design of an anti-inflammatory coating for invasive medical devices. Dissertation, LMU München: Faculty of Chemistry and Pharmacy
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Abstract

The prevention of material-mediated innate immune responses, which may lead to severe side effects, is an unsolved issue in invasive medicine. Neutrophil granulocytes are activated upon contact of blood with artificial material surfaces in medical devices. This unappreciated non-specific immune response provides a challenge for invasive medicine, since it may cause systemic inflammatory reactions and severe sequelae such as organ failure or even death. This thesis investigates the design an anti-inflammatory surface coating, which avoids or reduces material-mediated innate immune responses on the example of the material polymethylpentene (PMP). PMP is a polymer, which is used as hollow fibers in medical devices like oxygenators enabling the exchange of oxygen and carbon dioxide in the blood. Therefore, a biofunctional anti-inflammatory coating has been developed to avoid material-mediated neutrophil activation during respiratory support. The biofunctional anti-inflammatory coating is based on the covalent coupling of the agonistic FasL-molecule APO010, the covalent coupling of albumin (Recombumin® alpha) to passivate the coating and an amino acid-based stabilizing formulation to enable stability and functionality of the coating even after ethylenoxid (EtO)-sterilization and subsequent storage of the device. To investigate the stability and functionality of the coating, different methods were established: an ELISA to investigate the stable coupling of the biofunctional coating, a sandwich ELISA to detect detached APO010 and a chemotaxis assay to investigate the reduction of neutrophil activity after incubation with the coating. The novel coating has been upscaled from laboratory scale (bench setting) to a serial production scale, whereby the methods from this work were able to show a rapid reduction of neutrophil activation by approx. 10 % after contacting the surface in the second serial production run and the stability of the surface coating even after accelerated aging for up to 82 days at 55 °C in the third serial production run. Three upscaling steps were performed to generate homogeneous distribution of the coating on the PMP matrix. The biofunctional anti-inflammatory coating is a new technology to reduce unappreciated material-induced immunogenic responses. In principle, it should be possible to transfer this technology to other surfaces. This could allow for expansion of the positive effects to other medical devices in direct blood contact and can possibly show the way for new biofunctional coatings in the medical device sector.