Combined local delivery of tacrolimus and stem cells in hydrogel for enhancing peripheral nerve regeneration. Issue 7 (3rd May 2021)

• Record Type: Journal Article
• Authors: Saffari, Tiam M.; Chan, Katelyn; Saffari, Sara; Zuo, Kevin J.; McGovern, Renee M.; Reid, Joel M.; Borschel, Gregory H.; Shin, Alexander Y.
• Is Part Of: Biotechnology and bioengineering. Volume 118:Issue 7(2021)
• Page Start: 2804
• Page End: 2814
• Publication Date: 2021-05-03
• Subjects: drug delivery -- nerve injury -- stem cells -- tacrolimus -- tissue engineering; Biotechnology -- Periodicals; Bioengineering -- Periodicals; 660.6
• DOI: 10.1002/bit.27799
• Languages: English
• ISSNs: 0006-3592

Abstract

Abstract: The 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. Abstract : Nerve tissue engineering is becoming more prominent as artificial or naturally derived biomaterials provide support for axonal growth and are carriers for nerve drug delivery applications at the same time. The use of 100 ng/ml of tacrolimus microspheres is feasible for in vivo applications and could be recognized as a novel delivery tool when combined with MSCs.