Nikola Cesarovic

Last Name

Cesarovic

First Name

Nikola

ORCID

0000-0001-6744-2928

Organisational unit

09667 - Falk, Volkmar / Falk, Volkmar

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Publications 1 - 10 of 89

Transdermal wires for improved integration in vivo
Kourouklis, Andreas P.; Kaemmel, Julius; Wu, Xi; et al. (2023)
Biomaterials Advances
Alternative engineering approaches have led the design of implants with controlled physical features to minimize adverse effects in biological tissues. Similar efforts have focused on optimizing the design features of percutaneous VAD drivelines with the aim to prevent infection, omitting however a thorough look on the implant-skin interactions that govern local tissue reactions. Here, we utilized an integrated approach for the biophysical modification of transdermal implants and their evaluation by chronic sheep implantation in comparison to the standard of care VAD drivelines. We developed a novel method for the transfer of breath topographical features on thin wires with modular size. We examined the impact of implant's diameter, surface topography, and chemistry on macroscopic, histological, and physical markers of inflammation, fibrosis, and mechanical adhesion. All implants demonstrated infection-free performance. The fibrotic response was enhanced by the increasing diameter of implants but not influenced by their surface properties. The implants of small diameter promoted mild inflammatory responses with improved mechanical adhesion and restricted epidermal downgrowth, in both silicone and polyurethane coated transdermal wires. On the contrary, the VAD drivelines with larger diameter triggered severe inflammatory reactions with frequent epidermal downgrowth. We validated these effects by quantifying the infiltration of macrophages and the level of vascularization in the fibrotic zone, highlighting the critical role of size reduction for the benign integration of transdermal implants with skin. This insight on how the biophysical properties of implants impact local tissue reactions could enable new solutions on the transdermal transmission of power, signal, and mass in a broad range of medical devices.
Patientenspezifische Annuloplastieringe für die Mitralklappenrekonstruktion
Gessat, Michael; Sündermann, Simon H.; Cesarovic, Nikola; et al. (2012)
Tagungsband der 11. Jahrestagung der Deutschen Gesellschaft für Computerunterstützte Radiologie and Chirurgie (CURAC)
Injection anaesthesia with fentanyl-midazolam-medetomidine in adult female mice: importance of antagonization and perioperative care
Fleischmann, Thea; Jirkof, Paulin; Henke, Julia; et al. (2016)
Laboratory Animals
Septaly Oriented Mild Aortic Regurgitant Jets Negatively Influence Left Ventricular Blood Flow-Insights From 4D Flow MRI Animal Study
Cesarovic, Nikola; Weisskopf, Miriam; Kron, Mareike; et al. (2021)
Frontiers in Cardiovascular Medicine
Objectives: Paravalvular leakage (PVL) and eccentric aortic regurgitation remain a major clinical concern in patients receiving transcatheter aortic valve replacement (TAVR), and regurgitant volume remains the main readout parameter in clinical assessment. In this work we investigate the effect of jet origin and trajectory of mild aortic regurgitation on left ventricular hemodynamics in a porcine model. Methods: A pig model of mild aortic regurgitation/PVL was established by transcatheter piercing and dilating the non-coronary (NCC) or right coronary cusp (RCC) of the aortic valve close to the valve annulus. The interaction between regurgitant blood and LV hemodynamics was assessed by 4D flow cardiovascular MRI. Results: Six RCC, six NCC, and two control animals were included in the study and with one dropout in the NCC group, the success rate of model creation was 93%. Regurgitant jets originating from NCC were directed along the ventricular side of the anterior mitral leaflet and integrated well into the diastolic vortex forming in the left ventricular outflow tract. However, jets from the RCC were orientated along the septum colliding with flow within the vortex, and progressing down to the apex. As a consequence, the presence as well as the area of the vortex was reduced at the site of impact compared to the NCC group. Impairment of vortex formation was localized to the area of impact and not the entire vortex ring. Blood from the NCC jet was largely ejected during the following systole, whereas ejection of large portion of RCC blood was protracted. Conclusions: Even for mild regurgitation, origin and trajectory of the regurgitant jet does cause a different effect on LV hemodynamics. Septaly oriented jets originating from RCC collide with the diastolic vortex, reduce its size, and reach the apical region of the left ventricle where blood resides extendedly. Hence, RCC jets display hemodynamic features which may have a potential negative impact on the long-term burden to the heart.
The Depolarization Amplitude of the Electromyogram is a Measure of End-Diastolic Ventricular Volume
Dual, Seraina A.; Hall, S.; Sauer, Mareike; et al. (2020)
The Journal of Heart and Lung Transplantation
Continuous Heart Volume Monitoring by Fully Implantable Soft Strain Sensor
Dual, Seraina A.; Llerena Zambrano, Byron; Sündermann, Simon; et al. (2020)
Advanced Healthcare Materials
Cardiothoracic open‐heart surgery has revolutionized the treatment of cardiovascular disease, the leading cause of death worldwide. After the surgery, hemodynamic and volume management can be complicated, for example in case of vasoplegia after endocarditis. Timely treatment is crucial for outcomes. Currently, treatment decisions are made based on heart volume, which needs to be measured manually by the clinician each time using ultrasound. Alternatively, implantable sensors offer a real‐time window into the dynamic function of our body. Here it is shown that a soft flexible sensor, made with biocompatible materials, implanted on the surface of the heart, can provide continuous information of the heart volume after surgery. The sensor works robustly for a period of two days on a tensile machine. The accuracy of measuring heart volume is improved compared to the clinical gold standard in vivo, with an error of 7.1 mL for the strain sensor versus impedance and 14.0 mL versus ultrasound. Implanting such a sensor would provide essential, continuous information on heart volume in the critical time following the surgery, allowing early identification of complications, facilitating treatment, and hence potentially improving patient outcome.
Geometry influences inflammatory host cell response and remodeling in tissue-engineered heart valves in-vivo
Motta, Sarah E.; Fioretta, Emanuela S.; Lintas, Valentina; et al. (2020)
Scientific Reports
Regenerative tissue-engineered matrix-based heart valves (TEM-based TEHVs) may become an alternative to currently-used bioprostheses for transcatheter valve replacement. We recently identified TEM-based TEHVs-geometry as one key-factor guiding their remodeling towards successful long-term performance or failure. While our first-generation TEHVs, with a simple, non-physiological valve-geometry, failed over time due to leaflet-wall fusion phenomena, our second-generation TEHVs, with a computational modeling-inspired design, showed native-like remodeling resulting in long-term performance. However, a thorough understanding on how TEHV-geometry impacts the underlying host cell response, which in return determines tissue remodeling, is not yet fully understood. To assess that, we here present a comparative samples evaluation derived from our first- and second-generation TEHVs. We performed an in-depth qualitative and quantitative (immuno-)histological analysis focusing on key-players of the inflammatory and remodeling cascades (M1/M2 macrophages, α-SMA+- and endothelial cells). First-generation TEHVs were prone to chronic inflammation, showing a high presence of macrophages and α-SMA+-cells, hinge-area thickening, and delayed endothelialization. Second-generation TEHVs presented with negligible amounts of macrophages and α-SMA+-cells, absence of hinge-area thickening, and early endothelialization. Our results suggest that TEHV-geometry can significantly influence the host cell response by determining the infiltration and presence of macrophages and α-SMA+-cells, which play a crucial role in orchestrating TEHV remodeling.
Tailoring crystallinity for hemocompatible and durable PEEK cardiovascular implants
Chen, Mary Jialu; Pappas, Georgios A.; Massella, Daniele; et al. (2023)
Biomaterials Advances
Polymers have the potential to replace metallic or bioprosthetic heart valve components due to superior durability and inertness while allowing for native tissue-like flexibility. Despite these appealing properties, certain polymers such as polyetheretherketone (PEEK) have issues with hemocompatibility, which have previously been addressed through assorted complex processes. In this paper, we explore the enhancement of PEEK hemocompatibility with polymer crystallinity. Amorphous, semi-crystalline and crystalline PEEK are investigated in addition to a highly crystalline carbon fiber (CF)/PEEK composite material (CFPEEK). The functional group density of the PEEK samples is determined, showing that higher crystallinity results in increased amount of surface carbonyl functional groups. The increase of crystallinity (and negatively charged groups) appears to cause significant reductions in platelet adhesion (33 vs. 1.5% surface coverage), hemolysis (1.55 vs. 0.75%∙cm−2), and thrombin generation rate (4840 vs. 1585 mU/mL/min/cm2). In combination with the hemocompatibility study, mechanical characterization demonstrates that tailoring crystallinity is a simple and effective method to control both hemocompatibility and mechanical performance of PEEK. Furthermore, the results display that CFPEEK composite performed very well in all categories due to its enhanced crystallinity and complete carbon encapsulation, allowing the unique properties of CFPEEK to empower new concepts in cardiovascular device design.
Cellular activation status in femoral shaft fracture hematoma following different reaming techniques – A large animal model
Teuben, Michel Paul Johan; Halvachizadeh, Sascha; Kalbas, Yannik; et al. (2022)
Journal of Orthopaedic Research
The local inflammatory impact of different reaming protocols in intramedullary nailing has been sparsely investigated. We examined the effect of different reaming protocols on fracture hematoma (FH) immunological characteristics in pigs. To do so, a standardized midshaft femur fracture was induced in adult male pigs. Fractures were treated with conventional reamed femoral nailing (group RFN, n = 6); unreamed femoral nailing (group UFN, n = 6); reaming with a Reamer Irrigator Aspirator device (group RIA, n = 12). Animals were observed for 6 h and FH was collected. FH-cell apoptosis and neutrophil receptor expression (Mac-1/CD11b and FcγRIII/CD16) were studied by flow cytometry and local temperature changes were analyzed. The study demonstrates that apoptosis-rates of FH-immune cells were significantly lower in group RIA (3.50 ± 0.53%) when compared with non-RIA groups: (group UFN 12.50 ± 5.22%, p = 0.028 UFN vs. RIA), (group RFN 13.30 ± 3.18%, p < 0.001, RFN vs. RIA). Further, RIA-FH showed lower neutrophil CD11b/CD16 expression when compared with RFN (mean difference of 43.0% median fluorescence intensity (MFI), p = 0.02; and mean difference of 35.3% MFI, p = 0.04, respectively). Finally, RIA induced a transient local hypothermia and hypothermia negatively correlated with both FH-immune cell apoptosis and neutrophil activation. In conclusion, immunologic changes observed in FH appear to be modified by certain reaming techniques. Irrigation during reaming was associated with transient local hypothermia, decreased apoptosis, and reduced neutrophil activation. Further study is warranted to examine whether the rinsing effect of RIA, specific tissue removal by reaming, or thermal effects predominantly determine local inflammatory changes during reaming.
NAD+ the disregarded molecule in cardiac metabolism
Biefer, Hector R.C.; Elkhal, Abdallah; Cesarovic, Nikola; et al. (2020)
European Heart Journal

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Nikola Cesarovic

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