A thermo-responsive sol–to–gel phase transition hydrogel for sustained delivery of mesenchymal stem cell-derived exosomes

Introduction: Mesenchymal stem cells-derived exosomes (MSC-Exo) have significant therapeutic potential in regenerative medicine but face challenges such as rapid systemic clearance and poor retention at target sites. In this study, a thermo-responsive sol-to-gel phase transition hydrogel based on sodium alginate (SA), cellulose nanofibrils (CNF) and poloxamer 407 (P407) was prepared for sustained delivery of MSC-Exo. Methods: The MSC-Exo loaded CNF/SA hydrogel was prepared, which was freeze-dried and then dispersed in the P407 solution at room temperature. The mixture of CNF/SA/MSC-Exo and P407 could undergo thermo-responsive sol-to-gel phase transition due to the thermosensitive property of P407, and thus the CNF/SA/MSC-Exo was encapsulated in the P407 gel at physiological temperature (37 °C). Results: Owing to the high degradation ratio of P404 gel and swelling ratio of CNF/SA hydrogel at physiological pH (∼7.4), sustained delivery of MSC-Exo from the gel was achieved with a high cumulative release of 80 % after 120 h. Cytotoxicity assay showed that the CNF/SA/P407 gel has excellent biocompatibility. Conclusions: These findings provide a feasible strategy to achieve the sustained delivery of Exo for regeneration therapy, giving valuable references for future research.