Dynamically crosslinked ECM-like hydrogels loaded with ROS-responsive drug nanoparticles for treating inflammation in myocardial infarction and stroke

Following a myocardial infarction (MI) or stroke, the excessive generation of reactive oxygen species (ROS) within a brief timeframe may induce a pronounced inflammatory reaction, which exacerbates the progression of the disease. Thus, there is an urgent need to design a biomaterial to inhibit the inflammatory response associated with MI and stroke. In this study, we designed a reversible extracellular matrix (ECM)-like hydrogel via borate ester crosslinking, which responds to the inflammatory microenvironment affected by MI and stroke. At the same time, we developed a new type of loaded polymer nanoparticle (TK-DA) that can respond to ROS in ischemic regions and release the anti-inflammatory drug dexamethasone. Ultimately, we integrated the nanoparticles and ECM-like hydrogel to fabricate a functional hydrogel. To verify the therapeutic effect of the functional hydrogel, we established two models of typical ischemic diseases, MI and stroke. The results showed that the hydrogel substantially reduced ROS levels and inflammation in vitro. Moreover, the results of the two in vivo animal models demonstrated that this functional hydrogel can effectively treat MI and stroke by suppressing inflammatory responses, mitigating apoptosis, and promoting neovascularization. In conclusion, the functional hydrogel strategy presents a universally applicable treatment approach for ischemic cardiovascular and cerebrovascular diseases, which are not limited solely to the treatment of MI and stroke, but also hold future potential for clinical applications.