4.3 Article

Immunocompatibility and non-thrombogenicity of gelatin-based hydrogels

Journal

CLINICAL HEMORHEOLOGY AND MICROCIRCULATION
Volume 77, Issue 3, Pages 335-350

Publisher

IOS PRESS
DOI: 10.3233/CH-201028

Keywords

Gelatin-based hydrogels; immune cells; platelets; in vitro testing; mouse model

Funding

  1. Helmholtz Association
  2. Europaische Sozialfonds (ESF)
  3. Helmholtz Postdoc Program 2012 [PD-064]

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This study demonstrated that gelatin-based hydrogels have good immunocompatibility and non-thrombogenicity, making them suitable for coating the blood-contacting surface of cardiovascular implants. Through in vitro and animal experiments, it was found that the hydrogels did not activate complement or induce reactive oxygen species in human blood, and showed compatibility with vessel functionality in tests. Further implantation tests in mice showed no adverse effects in spleen, liver, or kidney, indicating the potential of these materials for biomedical applications.
Immunocompatibility and non-thrombogenicity are important requirements for biomedical applications such as vascular grafts. Here, gelatin-based hydrogels formed by reaction of porcine gelatin with increasing amounts of lysine diisocyanate ethyl ester were investigated in vitro in this regard. In addition, potential adverse effects of the hydrogels were determined using the Hen's egg test on chorioallantoic membrane (HET-CAM) test and a mouse model. The study revealed that the hydrogels were immunocompatible, since complement activation was absent and a substantial induction of reactive oxygen species generating monocytes and neutrophils could not be observed in whole human blood. The density as well as the activation state of adherent thrombocyteswas comparable to medical grade polydimethylsiloxane, which was used as reference material. The HET-CAM test confirmed the compatibility of the hydrogels with vessel functionality since no bleedings, thrombotic events, or vessel destructions were observed. Only for the samples synthesized with the highest LDI amount the number of growing blood vessels in the CAM was comparable to controls and significantly higher than for the softer materials. Implantation into mice showed the absence of adverse or toxic effects in spleen, liver, or kidney, and only a mild lymphocytic activation in the form of a follicular hyperplasia in draining lymph nodes (slightly increased after the implantation of the material prepared with the lowest LDI content). These results imply that candidate materials prepared with mid to high amounts of LDI are suitable for the coating of the blood contacting surface of cardiovascular implants.

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