A High Content Screening Assay for Evaluation of Biomaterial‐Mediated Cell Fusion Processes

Rijckaert, B.; Neffe, Axel T.; Roch, Toralf; Gebauer, Tim; Pierce, Benjamin F.; Görs, Julia; Smink, Jeske J.; Gossen, Manfred; Lendlein, Andreas; Leutz, Achim

doi:10.1002/masy.201400147

Cited by 2 publications

(1 citation statement)

References 35 publications

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“…In addition to the composition-dependent hydrolytic and enzymatic degradability in vitro, previous animal studies have shown that these hydrogels degraded in vivo completely without any signs of adverse tissue responses within 35 days (G10_LNCO3) to 84 days (G10_LNCO8). , Gelatin-based hydrogels supported the adherence and viability of arterial endothelial cells . However, it is well known that there is significant endothelial cell diversity.…”

Section: Introductionmentioning

confidence: 99%

Response of Endothelial Cells to Gelatin-Based Hydrogels

Krüger‐Genge

Hauser

Neffe

et al. 2021

ACS Biomater. Sci. Eng.

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The establishment of confluent endothelial cell (EC) monolayers on implanted materials has been identified as a concept to avoid thrombus formation but is a continuous challenge in cardiovascular device engineering. Here, material properties of gelatin-based hydrogels obtained by reacting gelatin with varying amounts of lysine diisocyanate ethyl ester were correlated with the functional state of hydrogel contacting venous EC (HUVEC) and HUVEC’s ability to form a monolayer on these hydrogels. The density of adherent HUVEC on the softest hydrogel at 37 °C (G’ = 1.02 kPa, E = 1.1 ± 0.3 kPa) was significantly lower (125 mm–1) than on the stiffer hydrogels (920 mm–1; G’ = 2.515 and 5.02 kPa, E = 4.8 ± 0.8 and 10.3 ± 1.2 kPa). This was accompanied by increased matrix metalloprotease activity (9 pmol·min–2 compared to 0.6 pmol·min–2) and stress fiber formation, while cell-to-cell contacts were comparable. Likewise, release of eicosanoids (e.g., prostacyclin release of 1.7 vs 0.2 pg·mL–1·cell–1) and the pro-inflammatory cytokine MCP-1 (8 vs <1.5 pg·mL–1·cell–1) was higher on the softer than on the stiffer hydrogels. The expressions of pro-inflammatory markers COX-2, COX-1, and RAGE were slightly increased on all hydrogels on day 2 (up to 200% of the control), indicating a weak inflammation; however, the levels dropped to below the control from day 6. The study revealed that hydrogels with higher moduli approached the status of a functionally confluent HUVEC monolayer. The results indicate the promising potential especially of the discussed gelatin-based hydrogels with higher G’ as biomaterials for implants foreseen for the venous system.

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Section: Introductionmentioning

confidence: 99%

Response of Endothelial Cells to Gelatin-Based Hydrogels

Krüger‐Genge

Hauser

Neffe

et al. 2021

ACS Biomater. Sci. Eng.

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Immunocompatibility and non-thrombogenicity of gelatin-based hydrogels

Krüger‐Genge

Tondera

Hauser

et al. 2021

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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 thrombocytes was 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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A High Content Screening Assay for Evaluation of Biomaterial‐Mediated Cell Fusion Processes

Cited by 2 publications

References 35 publications

Response of Endothelial Cells to Gelatin-Based Hydrogels

Response of Endothelial Cells to Gelatin-Based Hydrogels

Immunocompatibility and non-thrombogenicity of gelatin-based hydrogels

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