Aug 2026· Journal of Controlled Release· Vol 398, pp.
115246
· 0 citations· 145 references
Medicine
TL;DR
Recent advancements in the development of polysaccharide-based and supramolecular hydrogels designed for cardiac repair and regeneration are reviewed emphasising their application as delivery vehicles for various drugs, bioactive compounds and biologics to provide their sustained local release enhancing therapeutic outcomes and minimising off-target and side effects.
Abstract
Cardiovascular diseases are the leading cause of death worldwide, from which myocardium infraction (MI) is the most common one. Treatment of MI patients is difficult mainly due to the limited regeneration capacity of the heart, derived from the low proliferative activity of cardiomyocytes. Moreover, local administration and retention of therapeutic molecules is also difficult to be executed in a constantly beating heart, making the development of delivery vehicles that can retain therapeutics at the damaged heart tissue, and release them at a sustained rate, an unmet clinical need. Herein we review recent advancements in the development of polysaccharide-based and supramolecular hydrogels designed for cardiac repair and regeneration emphasising their application as delivery vehicles for various drugs, bioactive compounds (e.g., peptides, growth factors, genetic material, etc.) and biologics (cells, secretomes, etc.) to provide their sustained local release (or improved retention and survival of delivered cells) enhancing therapeutic outcomes and minimising off-target and side effects.
Cardiovascular disease remains the leading cause of death globally. In particular, ischemic heart disease represents the most common condition in clinics. Adult hearts have minimal regenerative capacity. Upon myocardial infarction, the formation of activated myofibroblasts replaces the massive loss of cardiomyocytes. Nanomedicine has emerged as a promising strategy for cardiovascular disease treatment, with synthetic nanoparticles and extracellular vesicles serving as representative delivery platforms. However, directly applying these nanomedicines faces several challenges, including insufficient cardiac targeting, poor retention rate at the injured site, and potential biocompatibility concerns. To overcome these limitations, different bioengineering approaches have been adopted. In this review, we discussed the landscape of cardiovascular nanomedicine, encompassing both synthetic nanocarriers and biological carriers and targeted delivery. We further evaluated the engineering approaches to enhance carrier performance. Multiple administration routes are also compared. Collectively, these advances represent a shift toward an integrated, multifunctional delivery platform with the potential to translate cardiac nanomedicine from bench to bedside.
The interactions between matrix composition, its capacity to protect therapeutic factors and enhance cell retention, and therapeutic release profiles that collectively regulate cardiac tissue repair outcomes are emphasized and emerging clinical applications and regulatory challenges for next-generation dcECM-based therapeutics are highlighted.
Jiazhu Xu, Zining Yang, Yufeng Wen et al.· Journal of Controlled Releas...· 0 citations
Simple Summary Cardiovascular diseases are the leading cause of death worldwide, accounting for 19.2 million deaths in 2023. When a heart attack occurs, the affected cardiomyocytes die rapidly, and the adult heart replaces them at only about 1% per year, far too slowly to compensate for the loss following a large infarction. Current treatments stabilise patients but cannot rebuild lost muscle. Over the past two decades, clinical trials have tested stem cells from bone marrow, fat tissue, umbilical cord blood, and reprogrammed adult cells. These approaches are consistently safe. Some have produced modest improvements in cardiac function and scar reduction, but the transplanted cells rarely persist long enough to form new heart muscle. The benefit they confer appears to arise mainly from signalling particles they release called extracellular vesicles and exosomes, which carry microRNAs and proteins that reduce scarring, stimulate blood vessel growth, and dampen post-injury inflammation. This finding has opened a new research direction: engineering those particles directly, without transplanting cells at all. This review examines the full range of cell-based strategies studied to date, the clinical trial evidence, the barriers to progress, and what engineered vesicles, bioengineered tissue constructs, gene editing, and improved trial design might offer.
Tissue and organ injury, degeneration, and functional loss represent a growing global health challenge, exacerbated by an aging population and the limitations of current clinical interventions. Regenerative medicine offers a promising alternative by restoring tissue function through the delivery of stem cells and their bioactive derivatives, particularly exosomes. However, direct administration of these therapeutic agents faces significant hurdles, including low retention, rapid clearance, and poor spatiotemporal control. Injectable microsphere-based delivery systems have emerged as a versatile and minimally invasive platform to overcome these limitations. This review systematically outlines the latest advances in microsphere-mediated strategies for delivering stem cells and their derivatives across multiple tissue types, including bone, cartilage, neural, skin, dental pulp, cardiac and lung. We critically evaluate the design principles of natural and synthetic polymers, fabrication techniques such as microfluidics and electrospray, and the biological functions of microspheres in providing three-dimensional (3D) scaffolds, immune protection, and sustained release. Furthermore, we highlight emerging frontiers, including the delivery of novel regenerative cues such as apoptotic bodies and the integration of microsphere-based organoid models. This comprehensive analysis aims to accelerate the clinical translation of next-generation microsphere-enabled regenerative therapies.
This review systematically analyzes the key issues facing EV-based therapeutic strategies in their progression from experimental research to clinical application, providing a practical theoretical framework for EV-based myocardial repair therapies and clarifying the prospects for EVs in the treatment of MI.
Kaiyi Zhu, Jing Bai, Liangfu Xu et al.· Journal of Controlled Releas...· 0 citations
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