Search Results (226)

Silk fibroin (SF) has evolved from a traditional biopolymer to a leading regenerative medicine material. Its combination of mechanical strength, biocompatibility, tunable degradation, and molecular adaptability makes SF a unique matrix that is both bioactive and intelligent. Advances in hydrogel engineering have transformed SF from a passive scaffold into a smart, living hydrogel. These systems can instruct cell fate, sense microenvironmental signals, and deliver therapeutic signals as needed. By incorporating stem cells, progenitors, or engineered immune and microbial populations, SF hydrogels now serve as synthetic niches for organoid maturation and as adaptive implants for tissue regeneration. These platforms replicate extracellular matrix complexity and evolve with tissue, showing self-healing, shape-memory, and stimuli-responsive properties. Such features are redefining biomaterial–cell interactions. SF hydrogels are used for wound healing, musculoskeletal repair, neural and cardiac patches, and developing scalable organoid models for disease and drug research. Challenges remain in maintaining long-term cell viability, achieving clinical scalability, and meeting regulatory standards. This review explores how advances in SF engineering, synthetic biology, and organoid science are enabling SF-based smart living hydrogels in bridging the gap between research and clinical use. Full article

Cardiac muscle has limited proliferative potential; therefore, loss of cardiomyocytes is irreversible and can cause or exacerbate heart failure. Although both pharmacological and non-pharmacological therapies are available, these interventions act primarily on surviving myocardium to manage symptoms and reduce—rather than reverse—adverse remodeling. The only curative option for end-stage heart failure remains heart transplantation; however, its clinical use is severely constrained by the shortage of donor organs. Consequently, regenerative therapies have gained increasing attention as potential novel treatments. Among these, cardiomyocytes derived from patient-specific pluripotent stem cells (PSCs) represent a particularly promising experimental platform for cardiac regeneration. To evaluate the potential of PSCs for cardiac repair through both in vivo and in vitro approaches, we (1) examined the hallmarks of cardiomyocyte maturation and the regulatory systems that coordinate these processes, (2) reviewed recent advances in maturation protocols and derivation techniques, (3) discussed how the cellular microenvironment enhances maturation and function, and (4) identified current barriers to clinical translation. Importantly, we integrated developmental biology with protocol design to provide a mechanistic foundation for PSC-based regeneration. Specifically, insights from cardiac development—such as signaling pathways governing proliferation, alignment, and excitation-contraction coupling—were explicitly linked to the refinement of PSC differentiation and maturation protocols. This developmental perspective allows us to bridge pathology and stem-cell methodology, explaining how disruptions in native cardiac maturation can inform strategies to produce functionally mature PSC-derived cardiomyocytes. Finally, we assessed the clinical prospects of PSC-derived cardiomyocytes, highlighting both the most recent advances and the persistent translational challenges that must be addressed before widespread therapeutic use. Full article

Three-dimensional (3D) bioprinting is increasingly explored as a strategy for myocardial repair and regenerative medicine. Conventional 3D casting often yields heterogeneous cellularization, slow electromechanical maturation, and inadequate vascularization; by contrast, bioprinting places cells and biomaterials in predefined architectures to program alignment, stiffness, vascular pathways, and electrical coupling that better recapitulate native myocardium. This review focuses on cardiac-specific advances in 3D bioprinting. We compare major platforms (jetting, light-based, extrusion, and volumetric) and their trade-offs for cardiac applications; distill bioink design principles trending toward natural–synthetic hybrids, including conductive and shape-morphing components; and outline practical characterization readouts spanning rheology, print fidelity, swelling/degradation, and cardiac function. We also summarize cell sources and co-culture strategies. Applications surveyed include cardiac patches, engineered tissues, chambered constructs, and organoids. Finally, we discuss current limitations and potential future directions for 3D bioprinting cardiac tissues. Collectively, recent advances position 3D bioprinting to accelerate the realization of in vivo-like engineered heart tissues. Full article

Amyloid cardiomyopathy (ACM), driven by transthyretin (TTR) and immunoglobulin light chain (LC) amyloid fibrils, remains a major clinical challenge due to limited mechanistic understanding and insufficient preclinical models. Human-induced pluripotent stem cells (iPSCs) have emerged as a transformative platform to model ACM, offering patient-specific and genetically controlled systems. In this review, we summarize recent advances in the use of iPSC-derived cardiomyocytes (iPSC-CMs) in both two-dimensional (2D) monolayer cultures and three-dimensional (3D) constructs—including spheroids, organoids, cardiac microtissues, and engineered heart tissues (EHTs)—for disease modeling, mechanistic research, and drug discovery. While 2D culture of iPSC-CMs reproduces hallmark proteotoxic phenotypes such as sarcomeric disorganization, oxidative stress, and apoptosis in ACM, 3D models provide enhanced physiological relevance through incorporating multicellularity, extracellular matrix interactions, and mechanical load-related features. Genome editing with Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 further broadens the scope of iPSC-based models, enabling isogenic comparisons and the dissection of mutation-specific effects, particularly in transthyretin-related amyloidosis (ATTR). Despite limitations such as cellular immaturity and challenges in recapitulating aging-associated phenotypes, ongoing refinements in differentiation, maturation, and dynamic training of iPSC-cardiac models hold great promise for overcoming these barriers. Together, these advances position iPSC-based systems as powerful human-relevant platforms for modeling and elucidating disease mechanisms and accelerating therapeutic development to prevent ACM. Full article

Magnetic hydrogels are stimulus-responsive hydrogels with rapid response when placed in a magnetic field. Their properties include those of conventional hydrogels such as biocompatibility, viscoelasticity, and a high content of water, with the addition of magnetic actuation, magnetothermal conductivity, and magnetic resonance conferred by the magnetic particles. Their use in the biomedical field is constantly growing, with various applications such as drug delivery, hyperthermia treatment, theranostic, and tissue engineering. Since the research field of magnetic hydrogels is very dynamic, it is important to review the literature regularly to highlight the most recent insights of the field. In this review, we focused on the latest advances of magnetic hydrogels and give a large overview on their types, fabrication, properties, and applications in hyperthermia, drug delivery, wound healing, MRI, sensors, and tissue engineering (neural, cartilage, bone, and cardiac tissues). We concluded this review with challenges and future developments of magnetic hydrogels. Full article

Understanding the nonlinear mechanical behaviour of mitral valve chordae tendineae is critical for accurate biomechanical modelling in cardiac simulations. This study integrates high-resolution 3D finite element analysis with experimentally derived Cauchy stress–Green–Lagrange strain data to capture both material and geometric nonlinearities. A one-dimensional formulation incorporating strain-dependent elasticity and large deformation kinematics was developed and validated against 3D simulations in COMSOL Multiphysics. Calibrated using experimental stress–strain data and validated against high-fidelity 3D finite element simulations in COMSOL, it reveals that neglecting transverse deformation overestimates axial force by 7%. Cross-sectional area reduction during stretch remained consistently around 12%, underscoring the importance of Poisson effects. A polynomial fit to the strain-dependent modulus of elasticity enables efficient force prediction with excellent agreement to experimental data. These results advance the mathematical modelling of biological tissues with nonlinear hyperelastic behaviour, providing a foundation for patient-specific simulations and real-time predictive tools in cardiovascular engineering. Full article

Organ bioprinting is a rapidly evolving field designed to address the persistent shortage of donor organs by engineering patient-specific tissues that replicate the function and structure of natural organs. Despite significant technological advancements, bioprinting still faces major obstacles, including tissue rejection, inadequate vascularization, limited physiological functionality, and various ethical and translational challenges. In this review, we assess current bioprinting modalities, particularly extrusion-based printing, inkjet printing, laser-assisted bioprinting (LAB), and stereolithography/digital light processing (SLA/DLP), highlighting their individual strengths and limitations. We also explore different bioink formulations, focusing especially on hybrid bioinks as promising solutions to traditional bioink constraints. Additionally, this article thoroughly evaluates bioprinting strategies for four major organs: heart, liver, kidney, and pancreas. Each organ presents unique anatomical and physiological complexities, from cardiomyocyte immaturity and electromechanical mismatch in cardiac tissues to vascularization and zonation challenges in liver structures, intricate nephron patterning in kidney constructs, and immune rejection issues in pancreatic islet transplantation. Regulatory and ethical considerations critical for clinical translation are also addressed. By systematically analyzing these aspects, this review clarifies current gaps, emerging solutions, and future directions, providing a comprehensive perspective on advancing organ bioprinting toward clinical application. Full article

Janus hydrogels have attracted significant attention in materials science and biomedicine owing to their anisotropic dual-faced architecture. Unlike conventional homogeneous hydrogels, these heterogeneous systems exhibit structural and functional asymmetry, endowing them with remarkable adaptability to dynamic environmental stimuli. Their inherent biocompatibility, biodegradability, and unique “adhesion–antiadhesion” duality have demonstrated exceptional potential in biomedical applications ranging from advanced wound healing and internal tissue adhesion prevention to cardiac tissue regeneration. Furthermore, “hydrophilic–hydrophobic” Janus configurations, synergistically integrated with tunable conductivity and stimuli-responsiveness, showcase the great potential in emerging domains, including wearable biosensing, high-efficiency desalination, and humidity regulation systems. This review systematically examines contemporary synthesis strategies for Janus hydrogels using various technologies, including layer-by-layer, self-assembly, and one-pot methods. We elucidate the properties and applications of Janus hydrogels in biomedicine, environmental engineering, and soft robotics, and we emphasize recent developments in this field while projecting future trajectories and challenges. Full article

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease affecting 2–3 neonates every 10,000 live births. While prior research has highlighted associations of HLHS with specific chromosomal abnormalities and genetic mutations, the precise pathophysiology remains elusive. Despite early surgical intervention potentially allowing most HLHS patients to survive their critical heart disease with a single-ventricle physiology, patients frequently experience complications of arrhythmias and right ventricular heart failure, culminating in the need for an eventual heart transplant. Scarcity of suitable donors combined with limited understanding of mechanisms of development highlights the need for furthering our understanding of HLHS and alternative treatment options. Over the past decades, stem cell research has significantly advanced our understanding of cardiac conditions, repair, development, and therapy, opening the door for a new exciting field of regenerative medicine in cardiology with significant implications for HLHS. This review serves to provide a comprehensive overview of a much focused-on area related to HLHS. Specifically, we will first discuss the key pathophysiological basis and signalling molecules of HLHS. We then outline the emerging role of stem cell-based therapy, with a focus on adult stem cells and pluripotent stem cells (PSCs) in uncovering the pathophysiology of HLHS and optimising future treatment directions. Finally, we will also explore the latest and possible future directions of stem cell-derived techniques such as cardiac organoids and bioengineering cardiac tissues and their utility for investigating disease mechanisms, drug screening, and novel therapy for HLHF. Full article

Heart disease remains a leading cause of morbidity and mortality worldwide, necessitating the development of in vivo models for therapeutic development. Advances in biomedical engineering in the past decade have led to the promising rise of human-based engineered cardiac tissues (hECTs) using novel scaffolds and pluripotent stem cell derivatives. This has led to a new frontier of human-based models for improved preclinical development. At the same time, there has been significant progress in elucidating the importance of the immune system and, in particular, macrophages, particularly during myocardial injury. This review summarizes new methods and findings for deriving macrophages from human pluripotent stem cells (hPSCs) and advances in integrating these cells into cardiac tissue. Key challenges include immune cell infiltration in 3D constructs, maintenance of tissue architecture, and modeling aged or diseased cardiac microenvironments. By integrating immune components, hECTs can serve as powerful tools to unravel the complexities of cardiac pathology and develop targeted therapeutic strategies. Full article

Cardiogenesis and heart cell composition and function constitute fundamental areas of cardiovascular medicine research, and exploring their underlying mechanisms is closely tied to the goals of precision medicine. This review comprehensively examines the composition and functions of the heart from embryonic organogenesis to maturity, and highlights the main breakthroughs of treatment strategies associated with these processes. By elaborating on the spatiotemporally specific signaling pathways and transcriptional networks that drive heart organogenesis and progenitor cell fate determination during the pivotal stages of cardiac development, and by systematically presenting the molecular biomarkers and functional characteristics of the principal cell types in mature heart, the latest advancements in related applications are summarized, with a particular emphasis on breakthroughs in gene/cell therapy, organoid development, and tissue engineering and regenerative medicine. This paper provides a theoretical foundation for precision interventions and regenerative medicine in cardiovascular disease using an axis that integrates cardiogenesis, cellular architecture, and therapeutic translation. Full article

Spaceflight and microgravity (μg) environments induce numerous cardiovascular changes that affect cardiac structure and function, and understanding these effects is essential for astronaut health and tissue engineering in space. This review compiles and analyzes over 30 years of research on the impact of real and simulated μg on cardiomyocytes. A comprehensive literature search was conducted across five databases, and 62 eligible studies involving cardiac cells under μg or spaceflight conditions were compiled and analyzed. Despite the great heterogeneity in terms of cardiac model, microgravity platform, and exposure duration, multiple studies consistently reported alterations in Ca²⁺ handling, metabolism, contractility, and gene expression. Three-dimensional human-induced pluripotent stem cell-derived cardiomyocyte (HiPSC-CM) models generally showed enhanced tissue maturation and proliferation parameters, suggesting potential therapeutic benefits, while 2D models mostly exhibited stress-related dysfunction. In vivo simulated microgravity studies, such as the hindlimb unloading (HU) model, show structural and functional cardiac remodeling, and real μg studies confirmed various effects seen under the HU model in multiple rodent species. Thus, μg exposure consistently induces cardiac changes at the cellular and molecular level, while model choice, microgravity platform, and exposure duration critically influence the outcomes. Full article

Advancements in bioinks and three-dimensional (3D) printing and bioprinting have significantly advanced cardiovascular tissue engineering by enabling the fabrication of biomimetic cardiac and vascular constructs. Traditional 3D printing has contributed to the development of acellular scaffolds, vascular grafts, and patient-specific cardiovascular models that support surgical planning and biomedical applications. In contrast, 3D bioprinting has emerged as a transformative biofabrication technology that allows for the spatially controlled deposition of living cells and biomaterials to construct functional tissues in vitro. Bioinks—derived from natural biomaterials such as collagen and decellularized matrix, synthetic polymers such as polyethylene glycol (PEG) and polycaprolactone (PCL), or hybrid combinations—have been engineered to replicate extracellular environments while offering tunable mechanical properties. These formulations ensure biocompatibility, appropriate mechanical strength, and high printing fidelity, thereby maintaining cell viability, structural integrity, and precise architectural resolution in the printed constructs. Advanced bioprinting modalities, including extrusion-based bioprinting (such as the FRESH technique), droplet/inkjet bioprinting, digital light processing (DLP), two-photon polymerization (TPP), and melt electrowriting (MEW), enable the fabrication of complex cardiovascular structures such as vascular patches, ventricle-like heart pumps, and perfusable vascular networks, demonstrating the feasibility of constructing functional cardiac tissues in vitro. This review highlights the respective strengths of these technologies—for example, extrusion’s ability to print high-cell-density bioinks and MEW’s ultrafine fiber resolution—as well as their limitations, including shear-induced cell stress in extrusion and limited throughput in TPP. The integration of optimized bioink formulations with appropriate printing and bioprinting platforms has significantly enhanced the replication of native cardiac and vascular architectures, thereby advancing the functional maturation of engineered cardiovascular constructs. Full article

Pathologies of the heart (e.g., ischemic disease, valve fibrosis and calcification, progressive myocardial fibrosis, heart failure, and arrhythmogenic disorders) stem from the irreversible deterioration of cardiac tissues, leading to severe clinical consequences. The limited regenerative capacity of the adult myocardium and the architectural complexity of the heart present major challenges for tissue engineering. However, recent advances in biomaterials and biofabrication techniques have opened new avenues for recreating functional cardiac tissues. Particularly relevant in this context is the integration of biomimetic design principles, such as structural anisotropy, mechanical and electrical responsiveness, and tissue-specific composition, into 3D bioprinting platforms. This review aims to provide a comprehensive overview of current approaches in cardiac bioprinting, with a focus on how structural and functional biomimicry can be achieved using advanced hydrogels, bioprinting techniques, and post-fabrication stimulation. By critically evaluating materials, methods, and applications such as patches, vasculature, valves, and chamber models, we define the state of the art and highlight opportunities for developing next-generation bioengineered cardiac constructs. Full article

Background: Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) hold transformative potential for cardiovascular regenerative medicine, yet their clinical application is hindered by suboptimal mitochondrial maturation and metabolic inefficiencies. This systematic review evaluates targeted strategies for optimizing mitochondrial function, integrating metabolic preconditioning, substrate selection, and pathway modulation to enhance energy production and cellular resilience. Additionally, we examine the role of extracellular matrix stiffness and mechanical stimulation in mitochondrial adaptation, given their influence on metabolism and maturation. Methods: A comprehensive analysis of recent advancements in iPSC-CM maturation was conducted, focusing on metabolic interventions that enhance mitochondrial structure and function. Studies employing metabolic preconditioning, lipid and amino acid supplementation, and modulation of key signaling pathways, including PGC-1α, AMPK, and mTOR, were reviewed. Computational modeling approaches predicting optimal metabolic shifts were assessed, alongside insights into reactive oxygen species (ROS) signaling, calcium handling, and the impact of electrical pacing on energy metabolism. Results: Evidence indicates that metabolic preconditioning with fatty acids and oxidative phosphorylation enhancers improves mitochondrial architecture, cristae density, and ATP production. Substrate manipulation fosters a shift toward adult-like metabolism, while pathway modulation refines mitochondrial biogenesis. Computational models enhance precision, predicting interventions that best align iPSC-CM metabolism with native cardiomyocytes. The synergy between metabolic and biomechanical cues offers new avenues for accelerating maturation, bridging the gap between in vitro models and functional cardiac tissues. Conclusions: Strategic metabolic optimization is essential for overcoming mitochondrial immaturity in iPSC-CMs. By integrating biochemical engineering, predictive modeling, and biomechanical conditioning, a robust framework emerges for advancing iPSC-CM applications in regenerative therapy and disease modeling. These findings pave the way for more physiologically relevant cell models, addressing key translational challenges in cardiovascular medicine. Full article