In vitroelectrical stimulation of stem cells: a scoping review

Chemical cues have been extensively explored in tissue engineering (TE). However, biophysical cues, such as electrical stimulation (ES) have recently gained attention for their capacity to enhance stem cell (SC) viability, proliferation, and differentiation. This scoping review focused on the impact of space and methods of ES parameters, including voltage, electric field (EF), current, frequency, and duration, when SCs are seeded on scaffolds for TE applications. The review's PICOT question was: 'What is the optimal parameter space of external ES on SCs seeded on a scaffold in anin vitrocell culture?' Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews guidelines, publications were systematically searched and selected from PubMed, Web of Science, and Scopus databases up to April-2025. The predefined inclusion criteria required that publications: employed ES, involved the use of SCs, included seeding SCs on a scaffold, and were conducted in anin vitroexperimental setting.65 publications covering ES and SCs have been incorporated, acknowledging the interdisciplinary challenges in this research domain. This scoping review synthesises the ES literature, highlights challenges, and proposes optimal parameters for SCs in TEs. Our findings highlight the importance of integrating conductive scaffolds with ES. Specifically, results indicate that moderate EF intensities i.e. (<200 V m^-1) protocols under direct coupling stimulation enhance key physiological processes in SCs. These results introduce the therapeutic potential of integrating ES with TE, particularly in neural regeneration, cardiac repair, and wound healing. Achieving that relies on optimising ES parameters to effectively translatein vitrofindings into clinically viable regenerative therapies and contribute to the development of more effective ES strategies and lay the groundwork for future translational research in TE and regenerative medicine.