Decellularized liver matrix-based bioactive beads induce host-vasculature integrated embolization.

Abstract

Particle-based embolic agents are widely utilized in transarterial embolization (TAE) treatment. Currently available embolic particles are predominantly categorized as either non-degradable materials designed for permanent vascular occlusion or purely degradable materials intended for temporary embolization. Nevertheless, these embolic agents generally possess no inherent bioactivity to regulate the vascular microenvironment, thereby limiting their therapeutic efficacy. Here we developed gelatin-based bioactive embolic beads chemically conjugated with decellularized liver extracellular matrix to enable stable delivery of abundant regenerative biomolecular cues to the locoregional intra-arterial environment. Endovascular embolization of the bioactive embolic beads allowed the delivered regenerative factors to promote significant intravascular collagen deposition and neotissue formation, thereby ultimately achieving host-vasculature integrated embolization. Rabbit ear embolization model revealed endovascular integration in surrounding fine vessels as early as 5 days post-embolization, followed by complete integration in main vascular branches and full removal of the embolized target tissue within 30 days, demonstrating a remarkable improvement over clinically-used purely-biodegradable embolic particles. Such bioactive composite embolic system presents a promising platform for enhancing endovascular embolization performance. STATEMENT OF SIGNIFICANCE: This study explores the therapeutic potential of a decellularized liver extracellular matrix (ECM) as a bioactive component in embolic agents for transarterial embolization treatment. Unlike conventional embolic materials that solely induce physical occlusion, the ECM derived from a regenerative organ serves as a natural healing stimulus within the vascular microenvironment post-embolization. We demonstrate, for the first time, that encapsulation of the decellularized liver matrix promotes host-vasculature integration by enhancing collagen deposition and facilitating neotissue formation. This process induces a comprehensive embolization effect, effectively occluding not only the target vessels but also the surrounding microvasculature, thereby preventing revascularization through collateral feeding vessels and achieving superior therapeutic efficacy. This work opens a therapeutic avenue by enabling controlled vascular remodeling with bioactive embolic agents to enhance endovascular embolization therapy.