Jul 2026· Journal of Controlled Release· pp.
115203
· 0 citations· 262 references
Medicine
TL;DR
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.
Abstract
Decellularized extracellular matrix (dECM) materials derived from cardiac tissues have emerged as multifunctional biomaterials that recapitulate native microenvironmental cues while serving as controlled-release reservoirs of therapeutic agents and cells for cardiac repair. Recent advances have demonstrated that decellularized cardiac ECM (dcECM) hydrogels and patches can localize the release of angiogenic peptides, growth factors, or genes to promote neovascularization and mitigate adverse remodeling. Simultaneously, dcECM platforms have been applied to improve the survival and engraftment of stem cells, cardiomyocytes (CMs), and cardiac progenitor cells (CPCs) in infarcted myocardium, facilitating paracrine signaling and immune modulation. This review summarizes recent progress in the design and translational development of dcECM-based drug and cell delivery strategies for cardiac repair. We emphasized 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 and highlighted emerging clinical applications and regulatory challenges for next-generation dcECM-based therapeutics.
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.
Annalisa Perioli, Ariana Gomes, Rui L Reis et al.· Journal of Controlled Releas...· 0 citations
This review systematically examines the biogenesis of MSC-EVs, focusing specifically on exosomes, microvesicles, and apoptotic vesicles, and introduces an emerging approach utilizing engineered MSC aggregate-derived EVs inspired by organ morphogenesis.
Shi‐Han Mu, Rang Li, Peng‐fei Wang et al.· Burns & Trauma· 0 citations
Functionalization of cardiovascular implants is advancing to improve hemocompatibility, endothelialization, anti-inflammatory effects, and long-term patency. Conventional materials, including polymers, chemical grafts, and bioactive molecules, provide important biological benefits but do not fully replicate the complex biochemical and physiological cues of the native vascular microenvironment. Cell-derived materials, including decellularized extracellular matrix (dECM), cell membranes, extracellular vesicles (EVs), and secretomes, offer significant opportunities by preserving native structural proteins, adhesion molecules, lipid interfaces, and paracrine signaling factors. These biologically derived materials enhance endothelial repair, modulate inflammation, reduce neointimal hyperplasia, and promote vascular remodeling. Despite these advantages, substantial translational challenges remain, as many biofunctionalized implants exhibit inadequate coating adhesion, limited shear resistance, poor durability under pulsatile flow, and susceptibility to fatigue, delamination, or structural failure. This review summarizes recent advances in the functionalization and fabrication of cardiovascular implants using cell-derived materials, providing a systematic analysis of fabrication strategies, biological performance, mechanical properties, and device-specific challenges. Finally, we discuss common failure mechanisms, translational barriers, and future directions for developing scalable, mechanically robust, and clinically translatable cell-derived biomaterials for next-generation cardiovascular implants.
Md Lemon Hasan, Mohammad Faysal Al Mazid, Yeasin Khan et al.· Biomaterials Advances· 0 citations
Cellular therapies harnessing the potential of endothelial colony-forming cells (ECFCs) for therapeutic revascularization in patients with critical limb ischemia (CLI) have garnered much interest. However, limited cell persistence following intramuscular injection into ischemic tissues has prompted the development of biomaterials as cell-delivery platforms to support cell survival and enhance therapeutic outcomes. This study explored the use of hydrogels derived from human decellularized adipose tissue (DAT) as a cell-instructive platform for ECFC delivery. In vitro studies confirmed high initial ECFC viability at 1 day following encapsulation in the DAT hydrogels but revealed that cell viability and proliferation were reduced over time in culture as compared to ECFCs cultured on tissue culture polystyrene (TCP). However, the ECFCs cultured within the DAT hydrogels showed similar ECFC cell surface marker expression patterns compared to ECFCs cultured on TCP after 6 days in culture, supporting that their phenotype was maintained. Subsequent testing focused on comparing a low (2.4 × 105 cells) and high (1 × 106 cells) dose of ECFCs delivered in either saline or within DAT hydrogels in a femoral artery ligation-induced CLI (FAL-CLI) model in NOD/SCID mice over 35 days. Bioluminescence imaging results showed that the low dose of ECFCs delivered in DAT hydrogels demonstrated enhanced retention on days 14, 21, and 28 compared to delivery in saline. Despite this finding, there were no observed improvements in hindlimb perfusion between delivery strategies, which may be related to the robust collateral vessel formation observed in this model with a µCT-based angiography method. Overall, this work supports that DAT hydrogels can enhance localized ECFC retention following intramuscular injection in mice with femoral artery ligation but emphasizes that enhanced retention may be insufficient for improving functional vascular regeneration.
Agnes E. Terek, John T. Walker, G. Bell et al.· Journal of Functional Biomat...· 0 citations
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.
