Fabrication, characterization and in vivo assessment of cardiogel loaded chitosan patch for myocardial regeneration

Cell therapy is one of the promising approaches for cardiac repair, subsequently after infarction or injury. However, contemporary mesenchymal stromal/stem cell (MSCs) delivery strategies result in low retention and poor engraftment of donor cells, thus limiting the therapeutic efficacy. Here, we developed an engineered bio-mimetic cardiogel patch (EBCP) comprising of the native decellularized cardiac extracellular matrix (ECM) cardiogel and chitosan, leading to the efficient regeneration of injured myocardium. We also developed novel bio-adhesive that is capable of suture-free epicardial placement of EBCP to injured myocardium. We have illustrated the potential of the mussels-inspired bioadhesive system, which comprises gelatin catechol and partially oxidized chitosan, which relies on self-crosslinking capability, to promote wet adhesion. In vitro studies with isolated cardiogel promoted cell proliferation, adhesion, and migration while aiding cardiomyogenic dif-ferentiation. The EBCP's ability to protect cells from abrasion due to surrounding tissues in the myocardial infarction (MI) rat model makes it more desirable.Furthermore, the epicardial implantation of the EBCP loaded with MSCs improves the initial retention of cells and subsequent functional cardiac recovery with enhanced myocardial tissue restoration. Histological exami-nation showed the presence of EBCP and infiltration of cells to the infarcted heart tissue. The fast and facile synthesis of bioadhesive and major therapeutic benefits of EBCP make it a potential candidate for recuperating the ailing heart.

Automated summary

Cell therapy is a promising approach for cardiac repair, but current delivery strategies have limitations. This study developed an engineered cardiogel patch (EBCP) using native decellularized cardiac extracellular matrix (ECM) and chitosan, enabling efficient regeneration of injured myocardium. The study also introduced a novel bio-adhesive for suture-free placement of EBCP on injured myocardium. The EBCP showed potential in promoting cell proliferation, adhesion, migration, and cardiomyogenic differentiation, and protecting cells in a myocardial infarction (MI) rat model. The epicardial implantation of EBCP loaded with MSCs improved cell retention and cardiac recovery in the rat model.