Treatment of myocardial infarction via sodium alginate microsphere-mediated co-delivery of Corydalis yanhusuo ethanolic extract and mesenchymal stem cells

Persistent inflammatory responses and adverse ventricular remodeling following Acute Myocardial Infarction (MI) are critical factors driving the progressive decline of cardiac function. Traditional pharmacological strategies struggle to achieve effective long-term intervention at the level of tissue repair. The Corydalis yanhusuo ethanolic extract (CYEE) possesses demonstrated anti-inflammatory and antioxidant activities; however, its limited in vivo half-life and the difficulty in maintaining local effective concentrations hinder its efficacy. Concurrently, while mesenchymal stem cells (MSCs) exert therapeutic potential through paracrine and immunomodulatory mechanisms, their low viability within the intensely inflammatory microenvironment of the infarcted myocardium significantly restricts their clinical impact. In this study, a sodium alginate microsphere delivery system was developed using gas-assisted microfluidic technology to achieve the synergistic encapsulation and localized delivery of CYEE and MSCs. This oil-free and surfactant-free microsphere system exhibits excellent biocompatibility, enabling the sustained release of CYEE within the infarcted region to alleviate inflammation and oxidative stress for initial therapeutic intervention. Furthermore, it enhances MSCs viability and paracrine function by optimizing the local microenvironment. In vitro experiments demonstrated that the system significantly improved cell viability under inflammatory conditions and promoted migration and angiogenic capacity. In a rat MI model, synergistic delivery significantly improved cardiac function and attenuated myocardial fibrosis and adverse remodeling without evident systemic toxicity. These results indicate that combining CYEE-mediated microenvironmental regulation with the dynamic synergistic repair of MSCs provides a comprehensive therapeutic strategy with potential translational value for myocardial repair following infarction.