Biology subjects

Jockenhoevel, S.

Publications and source records attributed to Jockenhoevel, S..

3 recordsLinked to original sources

bioRxiv2025

Miniaturized Device for Assessing Calcification Propensity of Biohybrid Implants Under Continuous Flow

Biohybrid implants are a promising development for cardiovascular disease treatment but suffer from problems like thrombogenesis and calcification. However, testing and validating biohybrid implants can be difficult and expensive due to material handling, fabrication methods and specialty medium components. The devices used to test potential samples can be large and expensive, requiring significant amounts of cell culture medium to operate. Additional, conventional static cell culture conditions do not accurately represent the vascular environment as shear and mechanical forces play key roles in the development of calcification. To address these challenges, a miniaturized, dual-channel flow chamber was designed and validated that allowed for real-time visualization of biohybrid calcification in a physiological environment. Computational Fluid Dynamics simulations were performed to determine the flow characteristics that generated physiological shear stress homogeneously across the sample surface. Micro particle tracking velocimetry measurements validated the simulated shear stresses near the sample surface. Two implant materials used for biohybrid construction, bovine pericardium and polycarbonate urethane, were inserted in the device and exposed to a flowing calcification medium for 14 days. Fluorescent fetuin-A was introduced into the calcification medium for real-time calcification monitoring. The two materials were compared with matched samples calcified in a large fatigue tester for 14 days. Our results showed similar material calcification for bovine pericardium and no calcification for polycarbonate urethane in the large fatigue tester and in our newly developed device. Biohybrid textile-reinforced fibrin-based scaffold populated with vascular smooth muscle cells started to calcify over 7 days in calcification medium. We conclude that this platform will provide novel insights into the origin and progression of pathological calcification and its potentially harmful health effects, which can occur as a result of tissue or metabolic abnormalities, disease, or implantation of certain biomaterials, by providing the ability to monitor the progression of calcification in biohybrid implants in real time, while also minimizing the cost and size of samples and reagents required for testing.

bioengineering↗

bioRxiv2025

Evaluation of Tissue-Engineered Blood Vessels as Three-Dimensional In Vitro Testing System in Cardiovascular Research and Device Approval

BackgroundDisturbed crosstalk between endothelial cells (ECs) and vascular smooth muscle cells (SMCs) has an important role in atherosclerosis and restenosis after vascular intervention, however, the exact pathomechanisms are incompletely understood. Current preclinical testing models do not adequately recapitulate the complexity of human arteries. Here, we present tissue-engineered blood vessels (TEBVs) as a novel in vitro model and validate it for intimal hyperplasia. MethodsTEBVs fabricated from SMC suspended in fibrin gel, supported by a textile mesh, were seeded with ECs at various concentrations and subjected to arterial flow conditions in a bioreactor. In addition, TEBVs underwent plain old balloon angioplasty (POBA) and implantation of bare metal stents (BMS) and drug-eluting stents (DES) at day 7 after fabrication. TEBVs were dynamically conditioned in a bioreactor for 21 days in total and monitored by optical coherence tomography. ResultsTEBVs with absent or incomplete endothelial layer exhibited thicker vessel walls, more disorganized and misaligned collagen, and increased cellular proliferation compared with completely endothelialized TEBVs. POBA and stent implantation were feasible 7 days after TEBV fabrication. At 14 days post-intervention, POBA-treated TEBVs exhibited significantly thicker vessel walls than untreated controls and stented TEBVs, whereas stented TEBVs showed greater lumen diameters than unstented TEBVs. Endothelial strut coverage was significantly higher in BMS-treated compared with DES-treated TEBVs. Over the course of the conditioning period, levels of IL-6, IL-8, and MCP-1 were highest in medium samples from BMS-treated TEBVs compared to DES-treated TEBVs and compared to untreated controls. ConclusionsTEBVs are a promising approach towards an in vitro system for the study of intimal hyperplasia. Due to their similarity in size and wall thickness to human coronary arteries, TEBVs may also serve as a platform for testing new stent designs. Graphical AbstractTissue-engineered blood vessels (TEBV) fabricated from smooth muscle cell /fibroblast mixtures suspended in fibrin gel, supported by a textile mesh, were seeded with endothelial cells and conditioned in a bioreactor system for 21 days. Different endothelialization strategies resulted in differences in wall thickness. In addition, TEBVs underwent plain old balloon angioplasty (POBA) and stent implantation. POBA-treated TEBVs exhibited thicker vessel walls compared with non-treated TEBV controls and compared with stented TEBVs. We also observed significantly higher stent strut coverage with endothelial cells after implantation of bare metal stents (BMS) compared to drug-eluting stents (DES). TEBVs are a promising approach towards an in-vitro system for the study of intimal hyperplasia. Due to their similarity in size and wall thickness to human coronary arteries, TEBVs may also serve as a platform for testing new stent designs.

bioengineering↗

bioRxiv2023

Towards Biohybrid Lung Development? Inflammatory Conditions Disrupt Endothelial Layer Integrity on Gas Exchange Membranes

Systemic inflammation presents a significant challenge to the long-term function of biohybrid implants. While endothelialisation of biohybrid implants has been shown to improve device hemocompatibility, its feasibility under the influence of patients inflammatory status remains largely unexplored. To investigate this, we developed a controlled in vitro model which allows to study endothelial dysfunction under inflammatory stress. Endothelial cells were cultured on polydimethylsiloxane under physiological shear stress and exposed to lipopolysaccharide (LPS)-activated peripheral blood mononuclear cells (PBMCs), simulating inflammatory conditions. Endothelial morphology and confluence was assessed using immunohistochemistry and scanning electron microscopy. Leukocyte adhesion was evaluated directly as well as indirectly, using flow cytometry to analyse cell adhesion molecules. Quantitative PCR was used for gene expression analysis of inflammatory mediators. Notably, neither LPS nor PBMCs alone induced endothelial disruption, whereas their combination significantly impaired endothelial confluence: Inflammatory activation led to substantial loss of endothelial confluence, increased leukocyte adhesion, and elevated expression of adhesion molecules ICAM-1, VCAM-1, and E-selectin. Gene expression analysis highlights the upregulation of inflammatory mediators, such as IL-6, IL-8, IL-10, and MCP-1. This study underscores the challenges of implementing endothelialisation in biohybrid devices, particularly in patients with systemic inflammation. By considering translational hurdles, this work contributes to the development of clinically viable biohybrid constructs and highlights the importance of considering inflammatory dynamics when designing next-generation implants.

bioengineering↗