Biomaterial platforms for enhanced stem cell therapy in ischemic stroke

Ischemic stroke remains a leading cause of long-term disability worldwide, and existing therapies have a very limited capacity to repair lost neurons or restore brain function. This review examines how biomaterial-enhanced stem cell therapies can address these shortcomings by creating microenvironments that actively drive brain tissue regeneration. We propose a comprehensive framework for classifying neural repair biomaterials, emphasizing biological scaffolds, assisted stem cell tracking, and preconditioning strategies to enhance stem cell function. Within this framework, we systematically compare different material systems and cell types across shared therapeutic goals, identifying which design features are most effective for specific outcomes. The physical space or mechanical stimuli of biomaterials, along with their chemical environment, particularly the biological signals that affect cell adhesion or growth factors, play essential roles in morphological outcomes and therapeutic improvement. This review summarizes various strategies for modifying specific cellular functions; for instance, conductive polymers may promote neurite growth. We have preliminarily established design principles for the combined application of specific cell types and biomaterials, which may serve as a guiding strategy. However, clinical translation remains constrained by an incomplete understanding of the complex interactions among cells, materials, and the dynamically evolving microenvironment, as well as by systemic fragmentation spanning from model selection to manufacturing standards. A fundamental breakthrough will require a paradigm shift from passive scaffold support to mechanism-driven, active regulation. This demands smart materials that adaptively respond to oxidative stress, inflammation, and repair timelines; design principles rooted in cell-type-specific logic and signaling pathway depth; precise coupling of transplantation timing with the host's receptive window; and interdisciplinary integration of gene editing, 3D bioprinting, artificial intelligence, and rehabilitation technologies to construct personalized therapeutic systems capable of resolving biophysical topography, biochemical cues, and spatiotemporal dynamics. By precisely guiding cell delivery through bioengineered scaffolds and reconstructing synaptic networks in the damaged brain, the gap between fundamental discoveries and clinical reality can be bridged within a mechanism-driven design framework. This work underscores the urgent need to move from empirical approaches to rationally designed systems, paving the way for stroke therapies that achieve durable functional recovery.