Electroconductive Polypropylene Fumarate-Methoxy Polyethylene Glycol Nanofibers Containing Sitagliptin-Loaded Polypyrrole Nanoparticles for Cardiac Tissue Engineering

Abstract

Myocardial infarction, a leading cause of mortality worldwide, creates an urgent need for effective strategies to regenerate damaged heart tissue. In this study, a novel nanofibrous hydrogel scaffold based on polypropylene fumarate (PPF)-methoxy polyethylene glycol (mPEG) copolymer, enriched with sitagliptin-loaded polypyrrole (PPy) nanoparticles (PPy-S NPs) was developed, to enhance myocardial tissue regeneration. Sitagliptin was incorporated into the formulation as a pro-angiogenic agent known to stimulate the expression of angiogenesis-related genes. The PPF-mPEG copolymer (CP) was synthesized via a multi-step transesterification process, creating a hydrophilic scaffold that promotes cellular adhesion and proliferation. Characterization of the CP/PPy-S scaffold revealed a well-distributed nanofiber network with a mean fiber diameter of 117.43 nm. Swelling ratio analysis showed high water uptake, with CP/PPy-S nanofibers reaching peak swelling of 1603.23 on day 14. Degradation studies demonstrated progressive weight loss over 28 days, with CP/PPy-S nanofibers displaying a slightly higher degradation rate compared to other groups. Drug release profiles indicated sustained sitagliptin release from the nanofibers, achieving a cumulative release of 92.86 over 14 days. Cytocompatibility testing using H9C2 cardiomyocytes showed significant enhancement in cell viability on CP/PPy-S nanofibers compared to other samples. These findings demonstrate that the nanofibrous scaffold not only provides mechanical support but also offers controlled drug release and electrical conductivity, both of which are crucial for myocardial regeneration. The integration of sitagliptin and PPy nanoparticles promotes cell viability, angiogenesis, and tissue-specific properties, making this scaffold a promising candidate for cardiac tissue engineering applications.