Development and pre-clinical evaluation of responsive antiplatelet coatings for endovascular implants

• Applicants: Dr. Daniel Kaiser; Dr. Manfred Maitz
• Subject Area: Biomaterials
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 569778349

Endovascular neuro-interventional devices carry an inherent risk of thrombus formation on their surfaces, which can lead to vessel occlusion or the release of emboli. Most of these devices either lack anti-thrombogenic properties or rely solely on passive anti-thrombogenic mechanisms. Existing bioactive coatings primarily target the coagulation cascade and exhibit their anticoagulant effects irrespective of the actual requirement. This non-selective activity potentially increases the risk of hemorrhagic complications. Furthermore, neuro-interventions are predominantly performed in the arterial system, where thromboprophylaxis primarily targets platelet inhibition. This proposal aims to develop an antiplatelet hydrogel as a thromboresistant coating on neuro-interventional stents, releasing the platelet aggregation inhibitor eptifibatide adjusted to the local hemostatic activity. The bioactivity, release characteristics, and stability of the hydrogel as a coating of neuro-interventional stents shall be evaluated using established in vitro assays. The antithrombotic properties of the coating shall be assessed during the development phase through in vitro experiments, using blood from healthy donors in various whole-blood incubation systems under quasi-static, venous and arterial flow conditions. Data with higher clinical relevance shall be obtained by utilizing blood from patients undergoing systemic platelet aggregation inhibition prior to elective treatment of intracranial aneurysms in Chandler loop assays. The obtained in vitro data shall be correlated with clinical data. These in vitro studies shall be supplemented by in vivo implantation tests in the supra-aortic arteries of rabbits, chosen for their flow conditions, which closely mimic those of the human target location. Pre-clinical evaluation of this novel surface modification, both in a relevant animal model and in patient blood, shall provide a superior level of confidence in biosafety compared to standard studies. The research consortium benefits from a synergistic collaboration between a non-university research institute (Leibniz-Institut für Polymerforschung Dresden e.V., IPF), specializing in the development and analysis of blood-contacting surfaces, and a clinical university institute (Universitätsklinikum Carl Gustav Carus Dresden, UKD). The clinical partner provides access to patient blood samples and on-site laboratory facilities, enabling immediate blood incubations. Additionally, the clinical partner's animal facility, equipped with dedicated angiography capabilities, offers exceptional opportunities for testing the proposed release system in advanced pre-clinical analytical settings.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Matthias Gawlitza