Strategies for Biologically Guided Vascular Repair in Neuroendovascular Therapy Extracellular Vesicles, Ultrasound Microbubbles, and Bioresorbable Scaffolds

Background: Neuroendovascular devices can achieve immediate angiographic success yet fail at the site that ultimately matters: the healing vessel wall. Durable therapeutic benefit depends on stable endothelialization, organized thrombus remodeling, and resolution of inflammation rather than progression to thrombosis, restenosis, or recanalization. Summary: This review reframes vascular healing as the primary therapeutic target and synthesizes evidence supporting three complementary strategies for biologically directed device integration. Among these, bioresorbable scaffolds and surface-modified implants currently have the strongest neurovascular device evidence, though this evidence derives from extracranial animal models, demonstrating improved hemocompatibility, more favorable vascular integration, and reduced long-term foreign material exposure. Extracellular vesicles, including exosomes, combined with ultrasound microbubble-mediated delivery represent promising approaches for concentrating pro-repair signals at the device interface. However, supporting evidence remains largely extracranial, and clinical translation will require rigorous control of vesicle identity and manufacturing standards, evaluation under clinically relevant antiplatelet conditions, standardized acoustic dosing, and careful assessment of branch vessel and perforator safety. No published intracranial platform has yet integrated a biological payload, focal delivery, and temporary scaffolding into a single therapeutic system. We therefore propose a stepwise translational framework that evaluates each component incrementally using endpoints aligned with clinically relevant failure mechanisms. Key Messages: Future neuroendovascular therapies should be evaluated not only by immediate angiographic success but also by their ability to promote durable vascular healing. Key translational endpoints include surface thrombogenicity, endothelial coverage and function, quality of vascular remodeling, and preservation of branch vessel patency. A biologically directed approach to device integration may improve the long-term durability and safety of intracranial endovascular therapies.