Fig. 6: Encapsulation of exosomes in hydrogels by direct mixing of exosomes with the hydrogel precursor solution and the release of exosomes during degradation.

A Thermosensitive chitosan (CS) hydrogel for the sustained release of exosomes from hP-MSCs. (a) Optical images of the CS solution (I) and hydrogel (II). (b) Scanning electron microscopy image of the CS hydrogel. (c) The rheological properties of the CS hydrogel with temperature changes were analyzed by rheological measurements. (d) Sustained release of Exos from the CS hydrogel was tested by tracking Gluc signals using bioluminescence imaging (BLI) analysis. (e) In vivo monitoring of the retention of transplanted CS-Exos or Exos through the tracking of Gluc signals by BLI analysis. (f) The stability of the main functional molecule miR-126 in CS-Exos or Exos at 37 °C was assessed by real-time qPCR analysis. (g) Quantitative analysis of Gluc signals indicated the retention of Exos in (e). *p < 0.05, **p < 0.01. Reproduced with permission¹⁰². Copyright 2018, American Chemical Society. B MMP2-sensitive KMP2 hydrogel for the controlled release of MSC-EVs. (a) Schematic illustration of the KMP2 hydrogel for enhanced EV release and tissue repair. (b) Degradation of the KMP2 hydrogel with or without MMP2 was measured by gel mass loss. (c) In vitro release of EVs from KMP2 hydrogels in PBS or an MMP2 solution (0.4 or 4 mg/ml, n = 3). *p < 0.05, **p < 0.01, PBS group vs. MMP2_0.4 group; ^#p < 0.05, ^##p < 0.01, PBS group vs. MMP2_4 group; ^&p < 0.05, ^&&p < 0.01, MMP2_0.4 group vs. MMP2_4 group. (d) Real-time PCR analysis of Bax and Fas mRNA levels in HK2 cells. (e) Western blot analysis of ICAM-1 and IL-1β protein levels in HK2 cells. HK2 cells were exposed to hypoxia-reoxygenation (H/R) and were treated with 10 μg protein/ml fresh EVs or released EVs. *p < 0.05, **p < 0.01, H/R group vs. Con group; ^#p < 0.05, ^##p < 0.01, Fresh EVs group vs. H/R group. Reproduced with permission¹⁰³. Copyright 2019, Elsevier.