Background: Cardiovascular diseases remain a leading cause of mortality worldwide. Current therapies manage symptoms but have limited capacity for myocardial regeneration. Endogenous stem cell homing is a promising mechanism for cardiac repair; however, the short half-life and rapid degradation of signaling peptides limit efficacy. Controlled delivery strategies sustain peptide release and enhance stem cell recruitment to injured myocardium.

Objective: This systematic review evaluates controlled delivery strategies of signal peptides to promote endogenous stem cell homing and their impact on left ventricular ejection fraction (LVEF) recovery after myocardial infarction (MI).

Methods: PubMed, Scopus, and Web of Science were searched up to August 2025. Preclinical studies investigating controlled peptide delivery for stem cell homing in MI models were included. Outcomes included LVEF, infarct size, ventricular wall thickness, and angiogenesis, synthesized descriptively.

Results: Twelve preclinical studies, mostly in rat MI models, were identified. Delivery platforms included hydrogels, nanoparticles, peptide nanofibers, and composite biomaterials for sustained chemokine release. Most studies evaluated stromal cell-derived factor-1α (SDF-1α) or engineered analogs; others incorporated FGF-2, TIMP-3, and NRG-1. Delivery systems enhanced stem cell homing and improved cardiac repair, reflected by increased LVEF, reduced infarct size, thicker ventricular walls, and enhanced angiogenesis. Peptides were typically administered immediately post-MI, with follow-up from 4 to 12 weeks.

Conclusion: Controlled delivery of signal peptides is a promising strategy to enhance endogenous stem cell homing and improve cardiac function after MI. Further preclinical and translational studies are needed to optimize delivery and confirm long-term efficacy.

Keywords: Myocardial Infarction, Regeneration, Delivery System, Signal Peptide, Chemokines

Niloofar Bondariyan received her PharmD from Shiraz University of Medical Sciences, Iran. She has extensive experience as a research assistant in pharmaceutical laboratories and as a medical writer. Her research focuses on drug delivery systems with applications in cardiology and oncology. Niloofar has recorded three patents, published over 15 articles, and serves as a scientific reviewer for international journals. Over the past two years, she has primarily supported phase I–III oncology clinical trials. Her work bridges innovative pharmaceutical research with translational applications, aiming to advance therapies from bench to bedside.