Microfluidic platforms for precision delivery of therapeutic cells in regenerative and personalized medicine

Regenerative medicine increasingly relies on therapeutic cells such as mesenchymal stem cells and induced pluripotent stem cells, and engineered cellular constructs to repair and restore damaged tissues. However, clinical translation is constrained by challenges in maintaining viability, ensuring precise localization, achieving durable engraftment of transplanted cells, and producing sufficient numbers of clinically relevant cells. Microfluidic technologies are emerging as transformative tools to address these barriers by enabling precise manipulation of fluids, biomaterials, and cells at the microscale. In the context of therapeutic cell delivery, these platforms can improve early retention and engraftment compared with conventional injections, provide tighter control over delivered cell dose, preserve viability under defined shear conditions, enable site-specific placement of cell-laden carriers, and support immunoisolating or immunomodulatory architectures that enhance immune safety. These platforms provide controlled microenvironments that mimic native tissue architecture, regulate biochemical and mechanical cues, and support the scalable production of cell-laden carriers. Advances in microfabrication techniques, ranging from soft lithography and thermoplastics to 3D printing and hydrogel integration, have expanded device versatility, while embedded sensors enable real-time monitoring of cell state, metabolism, and differentiation. Beyond single-cell delivery, microfluidics facilitates the encapsulation, co-culture, and organoid assembly of cells, enabling multicellular systems with physiologically relevant interactions. Coupled with CRISPR-based genome editing and synthetic biology, these platforms allow the engineering of "smart" therapeutic cells with enhanced regenerative and immunomodulatory functions. Applications extend to microfluidic sorting for stem cell purification, controlled differentiation, and advanced manufacturing of immune cell therapies such as chimeric antigen receptor (CAR)T cells, alongside exosome-based strategies for precision delivery. Despite promising progress, challenges remain in regulatory standardization, large-scale manufacturing, and integration with clinical workflows. This review highlights state-of-the-art microfluidic approaches for controlled delivery of stem cells and engineered cells, emphasizing how these systems impact key delivery metrics such as retention, dose control, shear resilience, spatial targeting, and immune interfaces to advance precision regenerative medicine.