Nonexpansive biodegradable matrix promotes blood vessel organoid development for neurovascular repair and functional recovery in ischaemic stroke

Tissue engineering-based vascular reconstruction represents a promising therapeutic strategy for ischaemic stroke. However, in the confined stroke cavity, conventional implants are unable to simultaneously provide swelling-resistant support and growth-permissive internal space, which are crucial for effective revascularization. To address this limitation, we develop a bioinspired, non-expansive biodegradable matrix (NEBM) through covalent-non-covalent assembly of commercially available, clinical-grade natural polymers. We show that NEBM recapitulates key features of brain extracellular matrix-including porous microstructure and tissue-matched stiffness-to deliver structural stability. Moreover, its progressively degradable structure establishes a dynamic remodelling niche that directs cellular behaviour towards promoting angiogenesis. Compared with commercial Matrigel-based matrix, NEBM fosters blood vessel organoid development with higher vascular density, larger vessel diameters and more distinct arterial features. In both subcutaneous and stroke transplantation models, we find that NEBM facilitates the integration of blood vessel organoids with the host vasculature. Strikingly, this revascularization in stroke cavity stimulates neurogenesis, contributing to significant functional recovery. As such, our study provides valuable guidance to design clinically translatable matrices for organ repair and regeneration in confined environments.