Tissue-Specific Hydrogels Ameliorate Hepatic Ischemia/Reperfusion Injury in Rats by Regulating Macrophage Polarization via TLR4/NF-κB Signaling

Injectable acellular matrix hydrogels are proven to be potential translational materials to facilitate the repairment in various tissues. However, their potential to repair hepatic ischemia/reperfusion injury (IRI) has not been explored. In this work, we made hepatic acellular matrix (HAM) hydrogels based on the decellularized process and evaluated the biocompatibility and hepatoprotective effects in a rat IRI model. HAM hydrogels supported viability, proliferation, and attachment of hepatocytes in vitro. Treatment with HAM hydrogels significantly attenuated hepatic damage caused by IRI, as evidenced by hepatic biochemistry, histology, and inflammatory responses. Importantly, HAM hydrogels inhibited macrophage M1 (CD68/CCR7) differentiation but promoted M2 (CD68/CD206) differentiation. Additionally, TLR4/NF-κB signaling was found to be involved in the hepatoprotective effect of HAM hydrogels. Collectively, our study reveals that HAM hydrogels ameliorate hepatic IRI by facilitating M2 polarization via TLR4/NF-κB signaling.