An intracranial aneurysm is a pathological and permanent dilation of the wall of a cerebral artery. Once formed, an aneurysm cannot heal spontaneously and is at risk of rupturing. Aneurysm rupture is the leading cause of hemorrhagic strokes, with a mortality rate of nearly 45% and persistent neurological sequelae in survivors. Advances in medical imaging now allow for early detection of these lesions, paving the way for preventive treatment. Currently, approximately 70% of intracranial aneurysms are treated endovascularly, mainly using the coiling technique.
Coiling involves occluding the aneurysm sac with detachable metal coils, usually made of platinum, which are inserted endovascularly using a microcatheter during a minimally invasive procedure. The aim is to fill the aneurysm with a “packing” of coils in order to exclude the aneurysm from the bloodstream and induce thrombus formation. However, this approach is limited by the phenomenon of recanalization, characterized by the partial or total reappearance of blood flow in the aneurysm, linked in particular to the compaction of the coils, the resorption of the thrombus, and insufficient parietal healing. This phenomenon affects approximately 30% of patients and exposes them to a risk of rupture requiring monitoring or retreatment.
The objective of this thesis is to develop a new generation of endovascular coils aimed at reducing the rate of recanalization of aneurysms by improving their biological integration. The chosen strategy is based on the functionalization of the surface of platinum coils with fucoidan. This bioactive molecule is known to modulate the activity of growth factors and the inflammatory response. It also promotes thrombosis through its interaction with P-selectin in activated platelets. This approach aims to reinforce thrombus stability and promote lasting healing of the aneurysmal neck.
This work is part of a rapid industrial technology transfer process for bioactive coils and the marketing of these innovative devices. Currently, no bioactive coils are available on the market. With this industrial perspective in mind, all of the work was designed to integrate the constraints of industrial manufacturing, reproducibility, and regulations for implantable medical devices. Four methods for functionalizing platinum were developed and evaluated through physicochemical and biological characterizations (in vitro and in vivo) to demonstrate their safety, bioactivity, and industrial transferability. This work has led to a project currently in phase II of industrial development.