Wet adhesive hydrogel cardiac patch loaded with anti-oxidative, autophagy-regulating molecule capsules and MSCs for restoring infarcted myocardium

Hydrogel patch-based stem cell transplantation and microenvironment-regulating drug delivery strategy is promising for the treatment of myocardial infarction (MI). However, the low retention of cells and drugs limits their therapeutic efficacies. Here, we propose a prefixed sponge carpet strategy, that is, aldehyde-dextran sponge (ODS) loading anti-oxidative/autophagy-regulating molecular capsules of 2-hydroxy-β-cyclodextrin@resveratrol (HP-β-CD@Res) is first bonded to the rat's heart via capillary removal of interfacial water from the tissue surface, and the subsequent Schiff base reaction between the aldehyde groups on ODS and amino groups on myocardium tissue. Then, an aqueous biocompatible hydrazided hyaluronic acid (HHA) solution encapsulating mesenchymal stem cells (MSCs) is impregnated into the anchored carpet to form HHA@ODS@HP-β-CD@Res hydrogel in situ via click reaction, thus prolonging the in vivo retention time of therapeutic drug and cells. Importantly, the HHA added to outer surface consumes the remaining aldehydes to contribute to nonsticky top surface, avoiding adhesion to other tissues. The embedded HP-β-CD@Res molecular capsules with antioxidant and autophagy regulation bioactivities can considerably improve cardiac microenvironment, reduce cardiomyocyte apoptosis, and enhance the survival of transplanted MSCs, thereby promoting cardiac repair by facilitating angiogenesis and reducing cardiac fibrosis.