Programmable Microcarriers for Stem Cell Therapy: Advanced Fabrication Strategies, Stem Cell Fate Regulatory Function and Biomedical Applications.

Stem cells, with their self-renewal and multi-lineage differentiation potential, hold promise for tissue repair and intractable diseases treatment. Yet clinical translation of stem cell therapies has long been hindered by insufficient scalable stem cell manufacturing, stemness loss and functional decline in 2D expansion, and poor post-transplantation cell retention, unregulated fate control. Programmable microcarriers (MCs) paired with 3D dynamic culture offer an emerging strategy to address these bottlenecks and enable stem cell fate regulation. In this review, we systematically review advanced MC fabrication strategies for stem cell fate regulation, comparing features of emerging technologies (microfluidics, electrospraying, in-air microfluidics, integrated in situ functionalization) and their implications for programmable MC control and scalable manufacturing. We analyze how MCs modulate stem cell behaviors (adhesion, proliferation, stemness maintenance, differentiation) via synergistic static physicochemical cues and dynamic stimuli-responsive properties. We map the latest advances in functionalized MC-mediated stem cell therapy across osteochondral defects, autoimmune, skin, ophthalmic and neurodegenerative diseases. Finally, we pinpoint unresolved challenges for clinical translation of MC-stem cell system and outline key future research directions. This review offers a systematic roadmap for advancing programmable MC fabrication, clinical-grade stem cell biomanufacturing, and precise cell therapy development.