Myocardial infarction (MI) remains a major cause of heart failure because current interventions, while improving early survival, do not sufficiently promote cardiac repair or prevent long-term adverse remodeling. Microspheres have emerged as a versatile therapeutic platform for MI due to their injectability, high surface-to-volume ratio, and tunable structure. These particulate systems are already used clinically in other fields such as chemotherapy, hemostasis, and long-acting injectables, and they can be adapted to encapsulate diverse bioactive agents for local modulation of the infarct microenvironment and promotion of cardiac repair.
Design variables central to microsphere performance include particle morphology, diameter distribution, and choice of materials. Morphology and size govern tissue penetration, retention, and release kinetics, while material composition determines biodegradability, biocompatibility, and payload compatibility. Surface properties and functionalization further influence interactions with immune cells and extracellular matrix components. In MI applications, these design parameters are chosen to balance minimally invasive delivery with sustained local therapeutic action and favorable integration within cardiac tissue.
Several fabrication methods are routinely used to produce microspheres with differing characteristics and control. The review highlights four major techniques:
Each technique has distinct advantages and limitations related to size uniformity, payload stability, manufacturing scalability, and control of release behavior.
Microspheres can be delivered to the injured heart via multiple routes, each with implications for invasiveness, localization, and therapeutic effect. The main delivery routes discussed are:
Route choice affects microsphere retention, distribution, and capacity to modulate the infarct microenvironment.
Microspheres are versatile carriers for multiple therapeutic strategies in MI repair. They can be loaded with growth factors, small molecules, cytokines, or other bioactive agents to provide sustained, localized release. Beyond acellular payloads, microspheres can support cell therapy by providing a protective microenvironment for delivered cells or by serving as building blocks for three-dimensional engineered cardiac tissues. This modular use permits combination approaches where microspheres deliver biochemical cues while scaffolding cells or tissue constructs aimed at restoring structural and functional properties of the infarcted myocardium.
The review synthesizes preclinical work demonstrating proof-of-concept for microsphere-mediated modulation of the infarct microenvironment and promotion of cardiac repair. Emphasis is placed on design strategies that optimize release kinetics, minimize adverse immune responses, and enhance retention at the target site. Functionalization approaches and tailored material selection are highlighted as means to improve targeting, payload stability, and biological activity within the hostile post-infarct milieu.
While microspheres show promise for MI therapy, the review outlines limitations and translational challenges. These include manufacturing scalability, reproducibility of particle properties, ensuring payload stability during fabrication and storage, achieving sufficient retention and distribution in human myocardium, and demonstrating safety and efficacy in clinical trials. The authors discuss future perspectives aimed at overcoming these hurdles through advanced fabrication, rational material design, functionalization strategies, and integrated approaches that combine microspheres with cells or engineered tissues to accelerate clinical translation.
Microspheres offer a flexible platform for local delivery and microenvironment modulation in myocardial infarction therapy. By controlling morphology, size, materials, and fabrication method, microspheres can be tailored for specific delivery routes and therapeutic payloads, including bioactive agents and cell-based constructs. Preclinical evidence supports their potential to promote cardiac repair, but translation will require addressing manufacturing, targeting, and safety challenges. The review aims to inspire innovative strategies to optimize microsphere design and hasten clinical application in MI care.