Sustained release of bioactive IGF-1 from a silk fibroin microsphere-based injectable alginate hydrogel for the treatment of myocardial infarction

Low circulating levels of insulin-like growth factor 1 (IGF-1) have been correlated with an increased risk for cardiovascular diseases in humans. In this work, an injectable alginate hydrogel containing silk fibroin (SF) microspheres with the capability to sustain the release of IGF-1 was prepared to induce myocardial repair after myocardial infarction (MI). First, IGF-1 was physically adsorbed onto SF microspheres prepared by the coaxial needle system, and these IGF-1-containing microspheres were subsequently encapsulated into sodium alginate solutions at different concentrations (1.0-2.5%). Finally, this solution was crosslinked with 0.68% calcium gluconate solution to prepare the composite injectable hydrogel. The composite hydrogel prepared using a sodium alginate solution at a concentration of 1.5% could promote proliferation of H9C2 cardiomyocytes and reduce the cellular apoptosis rate under hypoxic conditions. The enzyme-linked immunosorbent assay results indicated that SF microspheres as microcarriers could effectively enhance the sustained release of IGF-1 from the hydrogels, causing the composite hydrogel to possess a better sustained release ability than the system without the SF microspheres. Moreover, echocardiography, hematoxylin-eosin staining, and Masson trichrome staining results indicated that an intramyocardial injection of the composite hydrogel into the peripheral region of a MI rat model could reduce the infarct size and improve the cardiac function after 28 days. The applications of such a composite hydrogel may comprise a powerful platform in cardiac tissue engineering.