Saffari, Tiam M.Chan, KatelynSaffari, SaraZuo, Kevin J.McGovern, Renee M.Reid, Joel M.Borschel, Gregory H.Shin, Alexander Y.2023-01-102023-01-102021-07Saffari, T. M., Chan, K., Saffari, S., Zuo, K. J., McGovern, R. M., Reid, J. M., Borschel, G. H., & Shin, A. Y. (2021). Combined local delivery of tacrolimus and stem cells in hydrogel for enhancing peripheral nerve regeneration. Biotechnology and Bioengineering, 118(7), 2804–2814. https://doi.org/10.1002/bit.277990006-3592, 1097-0290https://hdl.handle.net/1805/30889The application of scaffold-based stem cell transplantation to enhance peripheral nerve regeneration has great potential. Recently, the neuroregenerative potential of tacrolimus (a U.S. Food and Drug Administration-approved immunosuppressant) has been explored. In this study, a fibrin gel-based drug delivery system for sustained and localized tacrolimus release was combined with rat adipose-derived mesenchymal stem cells (MSC) to investigate cell viability in vitro. Tacrolimus was encapsulated in poly(lactic-co-glycolic) acid (PLGA) microspheres and suspended in fibrin hydrogel, using concentrations of 0.01 and 100 ng/ml. Drug release over time was measured. MSCs were cultured in drug-released media collected at various days to mimic systemic exposure. MSCs were combined with (i) hydrogel only, (ii) empty PLGA microspheres in the hydrogel, (iii) 0.01, and (iv) 100 ng/ml of tacrolimus PLGA microspheres in the hydrogel. Stem cell presence and viability were evaluated. A sustained release of 100 ng/ml tacrolimus microspheres was observed for up to 35 days. Stem cell presence was confirmed and cell viability was observed up to 7 days, with no significant differences between groups. This study suggests that combined delivery of 100 ng/ml tacrolimus and MSCs in fibrin hydrogel does not result in cytotoxic effects and could be used to enhance peripheral nerve regeneration.en-USPublisher Policydrug deliverytacrolimustissue engineeringstem cellsArticle