Biohybrid Response Microparticles Decorated with Trained-MSCs for Acute Liver Failure Recovery

Microcarrier-based mesenchymal stem cells (MSCs) delivery have attracted increasing attention in acute liver failure (ALF) therapy, while there is still room for improvement in terms of improving cell loading efficiency, enhancing anti-inflammatory features, and controlling cell release. Here, novel lipopolysaccharide (LPS)-composited magnetic-thermal responsive inverse opal particles (MIOPs) are presented for the delivery of MSCs. The MIOPs are composed of a chitosan inverse opal skeleton filled with a hydrogel containing LPS, poly(N-isopropylacrylamide), and Fe₃ O₄ nanoparticles. Benefitting from the biocompatible chitosan component and the huge specific surface area, the resultant MIOPs can capture MSCs in a nondestructive way. Furthermore, LPS can be released from the MIOPs under the stimulation of an alternating magnetic field, by which the MSCs are activated to gain the feature of "trained immunity." Moreover, this process can be monitored in real-time by the structural color change of the MIOPs. With that, the MSCs-laden MIOPs are employed in rats with ALF, and they exhibit obvious anti-inflammatory and therapeutic efficacy superior to untrained MSCs. These performances make the MIOPs a distinctive cell delivery platform for clinical tissue recovery applications.