Smart bioactive hydrogels for myocardial infarction repair: a multifunctional approach integrating stimuli-responsive drug delivery, electroconductivity, and real-time biosensing.

Background: Myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide, necessitating advanced therapeutic strategies for cardiac repair. Conventional treatments often fail to restore cardiac function effectively, highlighting the need for innovative biomaterials. Smart bioactive hydrogels have emerged as promising candidates due to their ability to provide structural support, controlled drug delivery, electroconductivity, and real-time biosensing capabilities. Objective: This review explores the multifunctional role of smart bioactive hydrogels in MI repair, focusing on their stimuli-responsive drug delivery, electroconductive properties, and biosensing potential. Methods: This narrative review synthesized recent advances in multifunctional smart bioactive hydrogels for MI repair, focusing on systems integrating stimuli-responsive drug delivery, electroconductivity, and real-time biosensing. A comprehensive literature search was conducted in PubMed, Scopus, Web of Science, and Google Scholar for studies published between 2010 and 2025 using relevant keywords. Articles were included if they addressed hydrogel-based platforms featuring at least one of the following: responsive drug release (e.g., pH, temperature, and enzymatic), conductive components (e.g., carbon nanotubes and graphene), or embedded biosensing technologies. Studies limited to conventional hydrogels without multifunctionality were excluded. Relevant data were extracted and thematically categorized by material composition, functional properties, regenerative potential, and translational applicability, with emphasis on preclinical cardiac models. No quantitative synthesis was performed due to heterogeneity across study designs. Results: Smart bioactive hydrogels have demonstrated significant potential for MI repair by integrating stimuli-responsive drug delivery, electroconductivity, and biosensing within a single therapeutic platform. pH-, ROS-, and enzyme-sensitive systems enable localized, on-demand release of angiogenic factors or cardioprotective drugs, leading to 20-45% infarct size reduction and 1.5-2.3-fold increases in neovascular density in preclinical models. Incorporation of conductive materials such as graphene oxide (GO), polypyrrole, or carbon nanotubes (CNT) has been shown to restore electrical coupling, improve connexin-43 expression, and enhance left ventricular ejection fraction by 8-15%, while narrowing QRS complex duration by ~15 ms in large-animal studies. Emerging biosensing-enabled hydrogels permit real-time monitoring of local biochemical cues, such as pH, oxygen levels, and inflammatory cytokines, maintaining stable signal fidelity for up to 4 weeks without adverse tissue reactions. Advances in 3D/4D bioprinting now allow spatially patterned integration of these functionalities, enabling region-specific therapeutic release and conductivity optimization. Collectively, these multifunctional hydrogels exhibit superior regenerative outcomes compared to conventional scaffolds and hold strong translational promise, although variability in experimental design, lack of standardized endpoints, and limited long-term clinical data remain challenges to widespread adoption. Conclusion: Smart bioactive hydrogels represent a transformative approach in MI repair by combining structural support with multifunctional properties. Their ability to deliver therapeutics on demand, enhance electroconductivity, and enable real-time biosensing offers new possibilities for precision cardiac medicine.