Alleviation of renal ischemia-reperfusion injury by nitric oxide-releasing self-assembled peptide hydrogels

Aim and Background: Renal ischemia/reperfusion (I/R) injury is a global health problem with high clinical mortality and morbidity rate. Nitric oxide (NO) deficiency is known to play a key role in renal I/R injury; however, low stability and severe toxicity of high concentrations of NO have limited its applications. Thus, we developed an in-situ forming self-assembled peptide hydrogel releasing nitric oxide for renal I/R injury. Methods: Apart from physicochemical and rheological characterizations that confirmed entangled interlocking β-sheets with nanofibrous morphology, real-time RT-PCR, ROS production, serum biomarker concentrations and histopathological alterations were explored in a mouse model to assess the therapeutic efficacy of formulations in the treatment of renal I/R injury. Results and discussion: Peptide hydrogels self-assembled to the formation of an entangled nanofibrous and shear-thinning hydrogel. Hydrogels exhibited a sustained NO release over 7 days in a concentration-dependent manner. Importantly, intralesional injection of hydrogel caused superior recovery of renal I/R injury when compared to free NO in terms of histopathological scores. Compared to the I/R control group, oxidative stress and iNOS expression biomarkers showed a significant decline, whereas eNOS exhibited a significant increment, indicating regeneration of the injured endothelial tissue. Conclusion: Taken together, the novel self-assembled peptide hydrogel can be recommended for the alleviation of renal I/R injuries.