TY - JOUR A1 - Lau, Skadi A1 - Liu, Yue A1 - Maier, Anna A1 - Braune, Steffen A1 - Gossen, Manfred A1 - Neffe, Axel T. A1 - Lendlein, Andreas T1 - Establishment of an in vitro thrombogenicity test system with cyclic olefin copolymer substrate for endothelial layer formation JF - MRS communications / a publication of the Materials Research Society N2 - In vitro thrombogenicity test systems require co-cultivation of endothelial cells and platelets under blood flow-like conditions. Here, a commercially available perfusion system is explored using plasma-treated cyclic olefin copolymer (COC) as a substrate for the endothelial cell layer. COC was characterized prior to endothelialization and co-cultivation with platelets under static or flow conditions. COC exhibits a low roughness and a moderate hydrophilicity. Flow promoted endothelial cell growth and prevented platelet adherence. These findings show the suitability of COC as substrate and the importance of blood flow-like conditions for the assessment of the thrombogenic risk of drugs or cardiovascular implant materials. Y1 - 2021 U6 - https://doi.org/10.1557/s43579-021-00072-6 SN - 2159-6867 VL - 11 IS - 5 SP - 559 EP - 567 PB - Springer CY - Berlin ER - TY - JOUR A1 - Lau, Skadi A1 - Maier, Anna A1 - Braune, Steffen A1 - Gossen, Manfred A1 - Lendlein, Andreas T1 - Effect of endothelial culture medium composition on platelet responses to polymeric biomaterials JF - International journal of molecular sciences N2 - Near-physiological in vitro thrombogenicity test systems for the evaluation of blood-contacting endothelialized biomaterials requires co-cultivation with platelets (PLT). However, the addition of PLT has led to unphysiological endothelial cell (EC) detachment in such in vitro systems. A possible cause for this phenomenon may be PLT activation triggered by the applied endothelial cell medium, which typically consists of basal medium (BM) and nine different supplements. To verify this hypothesis, the influence of BM and its supplements was systematically analyzed regarding PLT responses. For this, human platelet rich plasma (PRP) was mixed with BM, BM containing one of nine supplements, or with BM containing all supplements together. PLT adherence analysis was carried out in six-channel slides with plasma-treated cyclic olefin copolymer (COC) and poly(tetrafluoro ethylene) (PTFE, as a positive control) substrates as part of the six-channel slides in the absence of EC and under static conditions. PLT activation and aggregation were analyzed using light transmission aggregometry and flow cytometry (CD62P). Medium supplements had no effect on PLT activation and aggregation. In contrast, supplements differentially affected PLT adherence, however, in a polymer- and donor-dependent manner. Thus, the use of standard endothelial growth medium (BM + all supplements) maintains functionality of PLT under EC compatible conditions without masking the differences of PLT adherence on different polymeric substrates. These findings are important prerequisites for the establishment of a near-physiological in vitro thrombogenicity test system assessing polymer-based cardiovascular implant materials in contact with EC and PLT. KW - cyclic olefin copolymer KW - poly(tetrafluoroethylene) KW - endothelial cells KW - platelets KW - in vitro thrombogenicity testing Y1 - 2021 U6 - https://doi.org/10.3390/ijms22137006 SN - 1422-0067 SN - 1661-6596 VL - 22 IS - 13 PB - Molecular Diversity Preservation International CY - Basel ER - TY - JOUR A1 - Lau, Skadi A1 - Gossen, Manfred A1 - Lendlein, Andreas T1 - Designing cardiovascular implants taking in view the endothelial basement membrane JF - International journal of molecular sciences N2 - Insufficient endothelialization of cardiovascular grafts is a major hurdle in vascular surgery and regenerative medicine, bearing a risk for early graft thrombosis. Neither of the numerous strategies pursued to solve these problems were conclusive. Endothelialization is regulated by the endothelial basement membrane (EBM), a highly specialized part of the vascular extracellular matrix. Thus, a detailed understanding of the structure-function interrelations of the EBM components is fundamental for designing biomimetic materials aiming to mimic EBM functions. In this review, a detailed description of the structure and functions of the EBM are provided, including the luminal and abluminal interactions with adjacent cell types, such as vascular smooth muscle cells. Moreover, in vivo as well as in vitro strategies to build or renew EBM are summarized and critically discussed. The spectrum of methods includes vessel decellularization and implant biofunctionalization strategies as well as tissue engineering-based approaches and bioprinting. Finally, the limitations of these methods are highlighted, and future directions are suggested to help improve future design strategies for EBM-inspired materials in the cardiovascular field. KW - endothelial cells KW - bioinstructive implants KW - vascular grafts KW - tissue KW - engineering KW - bioprinting KW - bioinspired materials KW - biological membrane KW - endothelial basement membrane KW - biomaterial Y1 - 2021 U6 - https://doi.org/10.3390/ijms222313120 SN - 1422-0067 VL - 22 IS - 23 PB - MDPI CY - Basel ER -