Search Results (191)

Exosomes are small membrane-bound extracellular vesicles of endosomal origin that play pivotal roles in intercellular communication by transferring proteins, lipids, metabolites, and nucleic acids. Increasing evidence indicates that these vesicles participate in diverse physiological and pathological processes, including immune regulation, tissue repair, tumor progression, neurodegeneration, and cardiovascular homeostasis. Their distinctive biological properties have consequently generated considerable interest in their development as diagnostic tools, therapeutic agents, and drug-delivery platforms. Recent progress in exosome biology and biogenesis, together with technological advances in vesicle isolation, characterization, engineering, and large-scale production, has accelerated their preclinical development and early clinical translation. Nevertheless, substantial challenges—including donor-cell heterogeneity, low production yields, insufficiently standardized protocols, and regulatory uncertainty—must be addressed before widespread clinical implementation can be achieved. This narrative review integrates current knowledge of exosome biology, diagnostic and therapeutic applications, and engineering strategies. It further examines major translational barriers and outlines future priorities for advancing exosome-based technologies toward precision medicine. Full article

Cardiovascular diseases (CVDs) remain the foremost cause of death globally, responsible for 19.2 million deaths and 437 million disability-adjusted life years in 2023, with prevalent cases having more than doubled since 1990. No approved therapy restores myocardium lost to infarction. The adult heart replaces cardiomyocytes at approximately 1% per year in young adults, declining to about 0.45% per year with ageing, far below what is needed to recover the more than one billion cells destroyed by a large myocardial infarction. Cell-based regenerative strategies have been investigated for more than two decades, encompassing bone marrow mononuclear cells (BM-MNCs), mesenchymal stromal cells (MSCs), cardiac progenitor cells, cardiosphere-derived cells (CDCs), skeletal myoblasts, and induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Safety has been consistent. Efficacy has been modest and variable: the CADUCEUS trial demonstrated scar mass reduction with CDCs without proportionate ejection fraction improvement; the Phase 1/2 POSEIDON trial confirmed MSC safety in 30 patients; and the Phase 3 DREAM-HF trial, enrolling 537 patients, failed its primary endpoint (HR 1.2, p = 0.406). Mechanistic work has established that transplanted cells engraft poorly and exert their benefit principally through paracrine signalling mediated by secreted extracellular vesicles and exosomes carrying microRNAs, trophic factors, and immunomodulatory proteins. For iPSC-CMs, electrophysiological immaturity and arrhythmogenic risk in primate models remain unresolved barriers. Emerging strategies include CRISPR-engineered hypoimmune iPSC lines, bioengineered cardiac patches, injectable hydrogel scaffolds, and engineered exosome platforms. This review provides a comprehensive synthesis of preclinical and clinical evidence, examines translational barriers, and identifies the scientific and regulatory priorities required before these therapies can enter routine clinical practice. Full article

The rising prevalence of cardiovascular diseases (CVDs) worldwide imposes a substantial economic burden on healthcare systems. Despite major advances in evidence-based therapies and modern healthcare, the demand for novel, time- and cost-effective treatment options continues to grow. Extracellular vesicles (EVs), including apoptotic bodies, microvesicles, and exosomes, are released by numerous cell types and mediate intercellular communication in both physiological and pathological contexts. To date, researchers have amassed compelling evidence for the functional roles of EVs in the development and progression of myocardial disease, supporting their exploration for clinical applications. In this review, we examine the multifunctional roles of EVs from diverse cellular origins in prominent CVD manifestations, highlighting publications of the last eight years and their key findings. They confirm that EVs carry disease-specific molecular cargo, particularly microRNAs, long non-coding RNAs, proteins, and other bioactive molecules, contributing to inflammation, oxidative stress, fibrosis, endothelial dysfunction, and cardiac remodeling, while also serving as promising diagnostic and prognostic biomarkers. Furthermore, emerging preclinical evidence demonstrates the therapeutic potential of engineered or tissue-derived EVs for promoting cardiac repair and limiting adverse cardiac remodeling. Full article

Cardiovascular diseases (CVDs) remain a leading source of morbidity and mortality worldwide. Although heart transplantation is an established treatment for selected patients with end-stage heart failure, the difficulty in obtaining enough donors and the problems associated with compatibility force the search for new strategies to mitigate these effects. Cardiac patches, a combination of therapeutic elements, such as cells and drugs deposited on a biomimetic scaffold, are particularly promising for repairing the long-term cardiac damage from a perspective based on tissue engineering. However, building these patches entails the compliance with extensive and exhaustive conditions and regulations. Key issues identified in the building process of cardiac patches are the cell–scaffold interaction, including the intensity and duration of this interaction. The present study is intended to develop a robust procedure that allows quantifying the adhesion between decellularized matrices and cells through single-cell force spectroscopy (SCFS) measurements. Determining this adhesion force is essential to ensure cell retention and therapeutic action in the damaged area and, therefore, to be able to design an advanced therapy medicinal product. The whole procedure is validated by measuring the adhesion of allogeneic adipose-derived mesenchymal stromal cells to a decellularized porcine myocardium patch. Full article

Biofabrication has significant potential to advance medicine and research by creating complex and anatomically accurate engineered tissues for implantation or in vitro modeling. However, a persisting challenge of the current biofabrication methods, such as hydrogel-based bioprinting, is to find an efficient, affordable, and reproducible method for the generation of hollow and branched geometries. This is critical for the recapitulation of anatomically realistic structures representative of cardiovascular, respiratory, and other organ systems. Existing bioprinting approaches require complex, multi-step processes and expensive specialized equipment, limiting accessibility and extending fabrication time. Here, we present an alternative ‘sacrificial’ method for the rapid and accessible creation of hollow and/or branched hydrogel constructs, which we term ‘soft templating’ (Sof-T). Sof-T utilizes ionic diffusion from a 3D-printed water-soluble polymer to crosslink surface-adsorbed hydrogels followed by the dissolution of the polymer, thus leaving behind the anatomically patterned hydrogels. Using this technique, we readily generated: (1) vascular-like bifurcated aortic conduits, with or without aneurysmal deformities; (2) upper and lower (branched) trachea models; and scale-reduced (3) human hearts and (4) bladders. Overall, Sof-T offers a simple, rapid, and cost-effective strategy for fabricating relatively complex, hollow hydrogel architectures, broadening the access to anatomically relevant constructs for biomedical research and translational and/or educational applications. Full article

Background/Objectives: Stem cells with the ability to differentiate into other cell types and self-renewal afford a powerful apparatus for the healthcare system to replace and rejuvenate damaged tissues and organs in the treatment of various diseases. For the last few decades, stem cell therapy (SCT) has evolved from being an experimental approach to a recognized clinical treatment. SCT and regenerative medicine have garnered tremendous attention and become prominent tools, especially in treating chronic and acute disease and addressing organ failures, and in their repair and replacement, which are directly associated with human health, life, and longevity. Methods: In this review, after providing a brief history and need for the SCT, the employed delivery techniques utilizing various biomaterials, as well as recent developments in nanotechnological methods, are presented. It is focused on the current literature for the recent progress of stem cell therapy and tissue engineering for the application fields in neurological, ophthalmological, cardiovascular, orthopedic, and oncology, followed by the challenges associated with their applications. Results: In addition to safety concerns, challenges such as uncontrollable differentiations, genetic and epigenetic instability, limited cell survival and integration, immunological rejections, scaling and manufacturing drawbacks, as well as unpredictable behaviors and clinical limitations were reviewed. Conclusions: Future aspects with respect to regenerative medicine and tissue engineering, gene editing and personalized therapies, immunomodulation and anti-inflammatory applications, as well as neuroregeneration and treatment of neurodegenerative disorders are reflected. Full article

Cardiovascular diseases remain the leading cause of mortality worldwide, highlighting the urgent need for more effective therapeutic strategies. Despite substantial advances in conventional biomaterials, their limited ability to support functional integration and dynamically interact with the biological microenvironment continues to hinder therapeutic outcomes. Native cardiovascular tissues rely on tightly regulated bioelectrical signaling to coordinate cellular communication, tissue homeostasis, and functional repair. Consequently, recreating these bioelectrical cues has emerged as a key design principle in cardiovascular tissue engineering. Electroactive biomaterials have gained increasing attention as a promising platform to address this challenge by enabling electrical modulation of cellular behavior and tissue function. In this review, we summarize the intrinsic bioelectrical properties of cardiovascular tissues and discuss the roles of electrical stimulation in regulating disease-relevant cellular responses. We further highlight recent advances in the development of conductive, piezoelectric, and other electroactive biomaterials for cardiovascular tissue engineering applications. Finally, we critically discuss the major challenges and future opportunities in the field, including tissue-specific responses, stimulation parameter optimization, long-term safety, and clinical translation. Collectively, electroactive biomaterials represent a promising and rapidly evolving frontier for the development of dynamic, responsive, and next-generation therapies for cardiovascular diseases. Full article

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, driving the continuous evolution of implantable cardiovascular therapies. Although early cardiovascular implants revolutionized the treatment of CVD, they are limited by restenosis, mechanical failure, poor biocompatibility, and inadequate tissue integration. These clinical limitations have driven the development of next-generation implants, with improved hemodynamic performance, regenerative potential, and long-term functionality. Advances in biomaterial science, tissue engineering, biosensors, wireless telemetry, flexible bioelectronics, and translational cardiovascular medicine have transformed cardiovascular implants from passive structural devices into biologically integrated and increasingly intelligent systems capable of interacting dynamically with the host cardiovascular environment. In this review, we summarize the historical evolution, current clinical applications, and emerging technologies of major cardiovascular implants. We further discuss key biological and engineering challenges limiting long-term clinical success and highlight future directions in regenerative biomaterials, smart bioelectronics, and personalized cardiovascular implants for next-generation cardiovascular therapy. Full article

Since current therapies cannot regenerate lost myocardium or reverse adverse ventricular remodeling—major contributors to worldwide cardiovascular mortality—advanced biomaterials, particularly hydrogels, have emerged as promising therapeutic platforms. Among these, bacterial nanocellulose (BNC) has gained increasing attention due to its hydrated nanofibrillar architecture, high crystallinity, robust mechanical performance, and excellent water-retention capacity, features that closely resemble key aspects of the native extracellular matrix. These properties provide a favorable microenvironment for cell adhesion, survival, and tissue organization in cardiovascular applications. Preclinical evidence suggests that BNC-based cardiac constructs, including acellular patches and cell-laden systems, may reduce post-infarction ventricular dilation, promote angiogenesis, and improve cellular engraftment. In vascular tissue engineering, BNC has also been explored in small-diameter grafts, anisotropic hydrogel systems, and shape-memory conduits with encouraging hemocompatibility and functional durability. Functional modifications—including gelatin incorporation, oxidative surface treatments, peptide grafting, conductive polymers, and structural alignment strategies—further expand the biological and mechanical versatility of BNC-based systems. In addition, BNC-containing bioinks have demonstrated promising rheological behavior, printability, and cell compatibility for 3D bioprinting applications. Despite these advances, important challenges remain, including optimization of material functionalization, host integration, degradation control, vascularization, scalable manufacturing, and regulatory translation toward clinical application. Full article

Biomechanics sits at the interface of engineering and medical sciences, offering essential insight into how tissues, organs, and biological systems respond to mechanical loading. This review brings together recent advances in musculoskeletal and cardiovascular biomechanics, illustrating how experimental techniques, computational modeling, and multiscale analysis are used to characterize load transfer, tissue deformation, fatigue, and injury mechanisms. In musculoskeletal applications, predictive simulations, wearable sensing technologies, and neuromechanical assessment tools support improved injury prevention, rehabilitation planning, and assistive device development. In the cardiovascular domain, patient-specific modeling, fluid–structure interaction analyses, and advanced imaging approaches clarify how hemodynamics, vessel wall mechanics, and device–tissue interactions influence disease progression, implant performance, and therapeutic outcomes. Emerging technologies including artificial intelligence, machine learning, digital twin frameworks, biofabrication, soft robotics, and self-powered sensing are enabling data-driven, real-time, and personalized interventions that connect mechanistic understanding with clinical practice. Despite these advances, challenges remain in accounting for individual variability, integrating multiscale data, and translating computational predictions into clinically validated solutions. By emphasizing interdisciplinary strategies that unite biomechanics, computational analytics, and innovative device engineering, this review outlines a pathway toward predictive, patient-centered healthcare and next-generation therapeutic and rehabilitation solutions. Full article

Lipid nanoparticles (LNPs) have become an important platform for the delivery of RNA therapeutics, including messenger RNA (mRNA) and small interfering RNA (siRNA). However, most clinically approved LNP formulations exhibit strong liver tropism following systemic administration, which limits efficient delivery to extrahepatic tissues. This inherent biodistribution profile has therefore been recognized as a key challenge for expanding the therapeutic applications of RNA nanomedicine. Recent efforts have focused on engineering functionalized LNP systems to improve delivery specificity beyond the liver. Surface modification with targeting ligands—such as antibodies, peptides, and nucleic acid aptamers—can promote receptor-mediated uptake by specific immune cell populations, including macrophages, dendritic cells and T lymphocytes. In parallel, advances in lipid design have improved intracellular RNA delivery by facilitating endosomal escape. These developments have broadened the potential use of RNA nanomedicine for inflammatory disorders, including autoimmune diseases, neuroinflammation, and cardiovascular inflammation. Functionalized LNPs are also being investigated for in vivo engineering of immune cells. This review summarizes current strategies for designing functionalized LNP systems, highlights their emerging applications in immune and inflammatory diseases, and discusses key challenges for clinical translation. Full article

Obesity is increasingly recognized as a disease of dysregulated intercellular communication rather than merely an energy imbalance. Extracellular vesicles (EVs), membrane-bound nanoparticles (30–1000 nm) released by nearly all cell types, act as central mediators of this pathological crosstalk. In obesity, hypertrophic adipocytes, pro-inflammatory macrophages, and dysfunctional endothelial cells secrete EVs carrying altered cargo, including pro-inflammatory miRNAs (e.g., miR-34a, miR-155), bioactive lipids, and stress proteins, which propagate systemic metabolic dysfunction. Adipose tissue-derived EVs impair hepatic fatty acid oxidation, promote steatohepatitis, suppress pancreatic beta-cell insulin secretion, induce skeletal muscle insulin resistance via PPARγ repression, and contribute to endothelial dysfunction and atherosclerosis. EV-mediated adipocyte–macrophage crosstalk reinforces chronic adipose inflammation. Circulating EVs also provide biomarkers: subpopulation ratios, miRNA signatures, and tissue factor-positive EVs reflect disease severity, predict cardiovascular risk, and monitor therapeutic responses, with machine learning enhancing diagnostic precision. Therapeutically, EVs from mesenchymal stem cells, Wharton’s jelly MSCs, adipose progenitors, and M2 macrophages reverse insulin resistance, hepatic steatosis, and adipose inflammation in preclinical models. Engineering strategies improve EV potency and tissue targeting, and Phase I trials confirm safety, though manufacturing and cost remain barriers. Preclinical and early clinical studies of MSC-EVs confirm a favorable safety profile, though manufacturing scalability and cost remain barriers to widespread clinical adoption. Overall, EVs represent both diagnostic tools and therapeutic vehicles in precision obesity medicine, offering a pathway from symptom management toward true disease remission. Full article

Myocardial infarction is a major cardiovascular event that leads to heart failure and death. Although current vascular regeneration and pharmacological therapies can salvage some myocardial tissue, they cannot effectively reverse established necrosis, fibrosis, or adverse ventricular remodeling, thus necessitating novel repair strategies. Silk fibroin (SF), a natural biomaterial, has emerged as an ideal substrate for cardiac tissue engineering owing to its excellent biocompatibility, tunable mechanical properties, and controllable biodegradability. This paper systematically reviews SF-based myocardial repair strategies: SF cardiac patches can be directly applied to infarct areas, providing mechanical support and delivering bioactive substances, while injectable SF hydrogels can be formed in situ via minimally invasive methods, serving as three-dimensional delivery vehicles for cells or drugs. These approaches synergistically promote cardiac repair through multiple mechanisms, including active regulation of inflammation, promotion of angiogenesis, and inhibition of fibrosis. Future development of SF-based therapies will focus on creating smart responsive materials, constructing biomimetic structures via advanced biomanufacturing techniques, and accelerating clinical translation, thereby providing comprehensive solutions for myocardial infarction repair. Full article

Marine algae, microalgae, and Cyanophyceae emerge as sustainable and versatile sources of biomacromolecules for the fabrication of hydrogels with broad biomedical potential. Their phycocolloids, such as alginate, agar, carrageenan, ulvan, and extracellular polysaccharides (EPS), exhibit intrinsic biocompatibility, tunable gelation behavior, and bioactive sulfated structures that support cell viability, tissue regeneration, and therapeutic delivery. This review provides a comprehensive overview of hydrogel fabrication strategies, including physical, chemical, and hybrid crosslinking approaches, and highlights recent advances in composite systems incorporating proteins, glycosaminoglycans, and functional nanomaterials. Applications in skin repair, cartilage and bone regeneration, neural and cardiovascular engineering, and controlled drug delivery are examined, alongside the expanding role of marine-derived hydrogels as bioinks for 3D and 4D bioprinting. Despite their promise, challenges remain related to extract variability, purification complexity, mechanical limitations, and the need for standardized characterization. Future perspectives emphasize genetic engineering of algae and cyanobacteria, development of multifunctional hybrid hydrogels, sustainable large-scale production, and pathways toward clinical translation. Together, these insights position marine-derived hydrogels as next-generation biomaterials with significant potential for regenerative medicine and therapeutic innovation. Full article

Background: The extracellular matrix (ECM) plays a central role in the mechanical strength and functional integration of tissue-engineered matrix (TEM), particularly in cardiovascular and load-bearing applications. Mesenchymal stromal cells (MSCs) from different sources may vary in their ECM-forming potential. Methods: In this study, adipose-derived (hADMSC), bone marrow-derived (hBMSC), and umbilical cord-derived MSCs (hUCMSC) were compared with human dermal fibroblasts (HDFBs) as a reference. Cells were seeded onto polyglycolic acid (PGA)/poly-4-hydroxybutyrate (P4HB) scaffolds and cultured for 3 weeks under static or hydrodynamic conditions using orbital shaking. TEM development was assessed macroscopically, histologically (using H&E and Masson’s trichrome stains), and by polarized light microscopy (Picrosirius Red), alongside biochemical assays that quantified DNA, glycosaminoglycan (GAGs), and hydroxyproline (HYP). Results: Hydrodynamically stimulated culture consistently improved ECM deposition across all groups. TEMs exposed to hydrodynamic stimulation (hydrodynamic conditions) were thicker, more uniformly filled, and exhibited increased collagen deposition compared with static TEMs, which remained thinner and showed persistent scaffold remnants. Polarized light analysis demonstrated that dynamic loading promoted collagen maturation in all groups, as evidenced by an increased prevalence of thick, birefringent collagen fibers indicative of mature collagen. Biochemical analyses showed that HDFB-derived TEMs produced the highest total collagen and ECM content under both static and hydrodynamic conditions; however, these matrices remained comparatively thin and densely packed. In contrast, MSC-derived TEMs formed thicker and more spatially distributed ECM in response to hydrodynamic stimulation. Conclusion: Among the MSC sources, hUCDMSC-derived TEMs exhibited the most advanced collagen maturation and the most uniform collagen distribution under hydrodynamically stimulated culture, whereas hADMSC-derived TEMs showed the greatest matrix thickening and volumetric ECM expansion with intermediate collagen maturation. hBMSC-derived TEMs displayed clear responsiveness to hydrodynamic stimulation but remained limited in overall collagen deposition and fiber maturation. These findings underscore that both hydrodynamic stimulation and cell source are critical not only for maximizing ECM deposition, but also for ensuring physiologically relevant collagen maturation and matrix organization in grafts suitable for clinical translation. Full article