Search Results (518)

Human induced pluripotent stem cells (hiPSCs) have revolutionized cardiovascular research by providing a renewable source of patient-specific cardiomyocytes for disease modeling, drug discovery, precision medicine, and regenerative therapies. Temporal modulation of canonical Wnt/β-catenin signaling has established the current gold standard for efficient and reproducible cardiac differentiation under chemically defined conditions. However, conventional Wnt-based protocols consistently generate cardiomyocytes with fetal-like structural, electrophysiological, metabolic, and contractile characteristics, highlighting that lineage specification alone is insufficient to achieve functional maturation. This review discusses recent advances in engineering the cardiac developmental niche by integrating extracellular matrix remodeling, biomaterials, biomechanical and bioelectrical stimulation, metabolic regulation, multicellular interactions, and microfluidic technologies to better recapitulate the dynamic microenvironment of human cardiogenesis. We further examine how emerging bioengineered platforms, including engineered heart tissues, cardiac organoids, and heart-on-chip systems, enhance the physiological relevance of hiPSC-derived cardiac models. Finally, we discuss future perspectives arising from the convergence of developmental biology, tissue engineering, biomaterials, artificial intelligence, and microphysiological systems, proposing that the next generation of cardiac differentiation platforms will depend on integrating canonical Wnt signaling within biomimetic developmental microenvironments to generate mature human cardiac tissues with enhanced translational potential. By advancing physiologically relevant human cardiac models for disease modeling, drug discovery, and regenerative medicine, this work also supports the research and innovation priorities underlying Sustainable Development Goal 3 (SDG 3), particularly those related to reducing the burden of non-communicable diseases and strengthening health-related research and development. Full article

Background/Objectives: Biomimetic biomaterials should be evaluated not only through their initial properties but also through their interaction with biological environments over time. This study investigated a human cell-based approach integrating flavonoid-induced cellular responses with the temporal evolution of 3D-printed polylactic acid (PLA) scaffolds under physiological-like conditions. Methods: Human Wharton’s Jelly mesenchymal stem cells (WJ-MSCs) were exposed to naringin and hesperidin (250 µg/mL) and evaluated after 3, 7, and 10 days using ALP, TP, OPN, and OC. In parallel, PLA scaffolds’ biodegradation was studied under static and dynamic conditions. Results: Naringin produced a more pronounced early/intermediate osteogenic-related response, whereas hesperidin showed comparatively more sustained ALP- and OPN-related activity at later stages. Dynamic scaffolds exhibited progressive temporal changes, with weight variations ranging from −0.384% to +0.127% at days 1, 3, 7, and 10, respectively, accompanied by progressive morphological modification. Initial AFM analysis showed an average RMS roughness of 22.1 nm. Conclusions: The distinct temporal profiles of the flavonoids, together with the evolving scaffold–medium interface, support a biomimetic strategy based on temporal coordination of biochemical cues. These findings provide a rationale for future experimentally validated sequential delivery systems designed to promote early osteogenic activation followed by sustained cellular and matrix-associated activity. Full article

Hydroxyapatite (HAp) is a promising biomaterial with potential environmental and biomedical applications; however, its surface properties and functional performance can be improved through polymer modification. In this study, a novel hydroxyapatite xanthan (HAp-XAn) composite was developed and investigated for both environmental and biomedical applications. Comprehensive structural and surface analyses were carried out using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and atomic force microscopy (AFM) measurements. The biocompatibility of HAp and the HAp-XAn composite was assessed with the aid of the MG63 cell line using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. The findings indicate that both HAp and HAp-XAn exhibit good in vitro cytocompatibility and favorable interactions with osteoblast-like cells, supporting their potential for use in bone-related biomedical applications. The antibacterial properties of HAp and HAp-XAn composites were studied in vitro against Staphylococcus aureus ATCC 25923 (S. aureus) and Escherichia coli ATCC 25922 (E. coli) bacterial strains. The results of the antibacterial assay revealed that HAp-XAn exhibited an improved antibacterial activity compared with HAp. The antibacterial assay highlighted that the inhibitory effect of HAp-XAn increased with the increase in incubation period. The HAp-XAn composite exhibited enhanced methylene blue (MB) adsorption compared with HAp, with the adsorption performance strongly dependent on pH, contact time, and initial dye concentration. Kinetic and equilibrium analyses indicated that the adsorption process was best described by the pseudo-second-order kinetic model and Langmuir isotherm. Overall, the incorporation of xanthan gum improved the adsorption and biological properties of HAp, demonstrating the potential of HAp-XAn as a multifunctional material for dye removal and biomedical applications. Full article

Agarose, a naturally derived marine polysaccharide extracted from red algae, has evolved from a conventional electrophoretic matrix into a multifunctional biomaterial platform for biomedical engineering. Its thermoreversible gelation, tunable pore structure, optical transparency, generally low immunogenicity under tested conditions, and chemical modifiability enable applications in tissue engineering, drug delivery, molecular diagnostics, immunomodulation, and cell preservation. This review critically examines recent advances in agarose-based biomaterials, with emphasis on structure–property relationships, stimulus-responsive delivery systems, regenerative scaffolds, immune–material interactions, agarose-enabled diagnostic microdevices, and DMSO-free cryopreservation. Representative developments include proof-of-concept microfluidic detection of a cfDNA surrogate and histones in spiked plasma, agarose composite hydrogels for controlled release and osteochondral repair, agarose-containing composite hydrogels investigated for macrophage modulation, and agarose/trehalose systems that provide immediate post-thaw viability comparable to conventional DMSO-based preservation in the reported cell model, although post-thaw proliferation remained lower. Agarose is commercially established in electrophoresis and bioseparation, whereas therapeutic delivery and implantable regenerative systems remain predominantly preclinical. Remaining barriers include limited in vivo degradability, insufficient intrinsic cell adhesiveness and bioactivity, trade-offs among mechanical strength, injectability and printability, and incomplete manufacturing and regulatory standardization. Future work should prioritize well-defined degradation pathways, reproducible composition–property relationships, application-specific benchmarking, and clinically relevant validation. Full article

The host immune response plays a central role in determining biomaterial performance, particularly through early macrophage activation dynamics at the tissue–biomaterial interface. This study evaluated the response of THP-1-derived human macrophages cultured on a fibrous extracellular matrix-like polydioxanone (PDO) mesh under basal (M0), M1-induced, and M2-induced in vitro conditions. Macrophage responses were assessed by gene expression analysis, immunofluorescence staining of macrophage- and polarization-associated markers, scanning electron microscopy (SEM), and metabolic and viability assays. Distinct stimulus- and time-dependent responses were observed across transcriptional, marker distribution, morphological, and metabolic readouts. Pro-inflammatory gene expression increased under M1-polarizing conditions at 72 h and declined at 96 h, whereas anti-inflammatory and M2-associated markers progressively increased under M2 stimulation, reaching higher levels at 96 h. Immunofluorescence confirmed macrophage differentiation under basal conditions and showed condition-dependent distributions of CD86- and CD206-associated signals, consistent with the transcriptional profiles. SEM revealed stable cell–material interactions and polarization-associated morphological heterogeneity. Metabolic and viability assays confirmed viable cells under all conditions, with activity patterns consistent with induced activation states. Under basal (M0) conditions, macrophages cultured on the PDO mesh maintained a basal phenotype without evidence of marked pro-inflammatory activation. Overall, these findings indicate that fibrous PDO meshes support macrophage viability, differentiation, and stimulus-responsive activation, highlighting their potential as immunologically compatible polymeric platforms for regenerative biomaterial applications. Full article

In vitro neurovascular unit (NVU) models are essential for reproducing blood–brain barrier (BBB) transport and neurovascular cell interactions. However, the literature remains fragmented: biomaterial chemistry, fabrication parameters and organ-on-a-chip architecture are commonly evaluated in isolation, while inconsistent reporting of matrix properties, processing history, cell source, flow and barrier readouts prevents head-to-head comparison and the extraction of transferable design rules. To address this gap, this review integrates biomaterials, manufacturing technologies and organ-on-a-chip engineering within a unified material–process–structure–function framework. We translate endothelial junctions, basement-membrane components and perivascular cells into experimentally actionable material requirements; compare natural, synthetic, semisynthetic and decellularized extracellular-matrix hydrogels; and examine crosslinking, peptide functionalization, stimuli responsiveness, composite-network formation and preparation methods. Findings from Transwell, microfluidic, tubular, self-assembled and 3D-bioprinted BBB systems are used to relate matrix stiffness, degradability, ligand density, permeability, device-body material and fabrication route to barrier maturation, analytical access and reproducibility. By defining matched controls and minimum reporting requirements for chemistry, mechanics, transport and processing, this review provides a practical basis for next-generation BBB models that can improve permeability and efficacy screening in drug discovery, reproduce disease- and patient-specific barrier dysfunction, and support individualized response testing with iPSC- or patient-derived cells. Full article

Insufficient vascularization remains a major limitation in tissue engineering, restricting the survival and maturation of larger bioengineered constructs. While candidate hydrogels are commonly characterized with regard to physicochemical properties, gelation behavior, mechanical performance, and cytocompatibility, simple functional assays that assess their capacity to support vascular sprouting are less frequently integrated into early-stage biomaterial evaluation. Here, we investigated the established ex vivo aortic ring assay (ARA) as an exploratory functional approach for the initial comparison of selected hydrogel formulations. Murine aortic rings were embedded in collagen I (Col I), alginate (Alg), or gelatin methacryloyl (GelMA) and cultured under control conditions or with vascular endothelial growth factor A (VEGF-A) stimulation. These hydrogels were intentionally selected as a proof-of-concept panel of representative, non-equivalent material classes with distinct expected cell-interactive properties. After five days, Col I supported robust capillary-like outgrowth that was further enhanced by VEGF-A, whereas the tested GelMA formulation supported only limited cellular migration and the tested unmodified Alg formulation showed no detectable sprouting under the conditions examined. Cluster of differentiation 31 (CD31) immunostaining supported the presence of an endothelial component within the Col I-supported sprouting structures. These findings demonstrate that the ARA can detect pronounced formulation-dependent differences among the specific hydrogels tested using straightforward morphological and immunostaining readouts. Within the scope of the formulations tested, these findings support the ARA as a complementary functional readout alongside conventional biomaterial characterization before more complex tissue engineering or biofabrication studies are performed. Full article

Carbohydrates are among the most highly oxygenated biomolecules in nature, possessing dense arrays of hydroxyl, ether, carbonyl, carboxylate, phosphate, and sulfate functionalities that govern hydration, hydrogen bonding, molecular recognition, and supramolecular organization. Their stereochemically organized oxygen-donor groups provide numerous appropriately oriented diol motifs capable of selective and reversible coordination with boric acid and borate ions. This review examines the structural and physicochemical principles underlying carbohydrate–borate interactions, with particular emphasis on oxygen-rich biological interfaces. Pentoses, hexoses, oligosaccharides, polysaccharides, glycolipids, and membrane-associated glycoconjugates are considered to illustrate how hydroxyl-group orientation, molecular conformation, pH, hydration, and local environment determine borate recognition, complex stability, and dynamic assembly. Evidence from NMR and other spectroscopic methods, crystallography, mass spectrometry, calorimetry, and molecular simulations demonstrates that borate coordination follows common stereochemical and thermodynamic principles despite the remarkable structural diversity of carbohydrates. Biological examples include borate-mediated crosslinking in plant cell walls and interactions involving microbial carbohydrates, marine polysaccharides and glycoconjugates, photosynthetic membrane lipids, and cyanobacterial heterocyst glycolipids. Particular attention is given to distinguishing experimentally established borate complexes from membrane-associated interactions that remain proposed and require further characterization. Reversible borate crosslinking of oxygen-rich carbohydrate networks also provides the chemical basis for emerging applications in responsive hydrogels, biosensors, supramolecular assemblies, drug-delivery systems, and functional biomaterials. Collectively, the available evidence indicates that the spatial organization of oxygen donor atoms within carbohydrates provides the molecular basis for selective borate recognition, whereas boron can convert this functionality into reversible higher-order organization. This oxygen-centered perspective integrates coordination chemistry, glycobiology, membrane biology, and materials science into a unified framework for understanding carbohydrate–borate interactions in natural and engineered systems. Full article

In the contemporary era of minimally invasive surgery, injectable biomaterial scaffolds have demonstrated significant potential in bone tissue engineering (BTE). Completely injectable hydrogel substratum with microscale bone graft particulates delivered through a needle-shaped orifice shifts a new paradigm for surgical interventions in clinical settings. Despite growing interest in biopolymer-based BTE systems, clinically applicable delivery platforms and a mechanistic understanding of cell–material interactions remain limited. This study developed a dual-syringe auto-mix system capable of generating an in situ cross-linking hydrogel–mineral construct composed of gelatin–hydroxyphenyl propionic acid, hyaluronic acid–tyramine, horseradish peroxidase, hydrogen peroxide, and calcium phosphate particles of varying sizes. Material distribution, rheological and mechanical properties, and swelling were characterized. Goat bone marrow-derived mesenchymal stem cells served as the basis for examining how the composite affected cell viability, morphology, proliferation, contractility, osteogenic differentiation, mineralization, and chemotactic behavior. To determine whether these biological findings were supported mechanically, an ex vivo cone-beam computed tomography model was used to evaluate volumetric stability and resistance to deformation at the graft–host interface. Cross-linking established a stable internal microarchitecture while remaining compatible with cell viability and nutrient-dependent survival. Formation of the gelatin–hyaluronan (GH) network significantly increased the storage modulus relative to gelatin (G) alone, whereas subsequent calcium phosphate incorporation (GH-CP) preserved this mechanical competence while attenuating the volumetric expansion of GH. These physical characteristics were accompanied by more organized cell morphology, enhanced osteogenic differentiation, and mineral deposition throughout a larger portion of the matrix. Heterogeneous interpenetrating gap striation (HIGS) appeared in regions of cellular aggregation and matrix deposition, and a new conceptualization of the osteogenic phenomenon, termed cling osteogenesis, has been proposed. These outcomes support an intricate relationship between early mechanical stabilization, mechanotransduction, and osteogenesis in injectable hydrogel–mineral systems. Full article

The nano-hydroxyapatite/β-tricalcium phosphate composite (nano-HA/β-TCP) is widely used in various medical and dental procedures. The absence of in vivo toxicity of nano-HA/β-TCP has been extensively studied, and it is considered one of the most effective synthetic biomaterials for promoting cell differentiation in bone regeneration. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are the primary cell type involved in the osteoinductive process of guided bone regeneration following injury. In the present study, rat BM-MSCs were cultured with nano-HA/β-TCP (80/20%) composite spheroids, and the interaction between the cells and the composite was analyzed using transmission electron microscopy (TEM). Ultrathin sections examined by TEM showed extensive interaction between nano-HA/β-TCP and BM-MSCs. Semi-thin sections stained with toluidine blue revealed the incorporation of the biomaterial into the cell cytoplasm. For the immunohistochemistry analysis, eight adult male Wistar rats weighing approximately 300 g were used in each group. Two bilateral, non-critical-sized 3 mm defects were created in the parietal bones of the calvaria: Control, Bio-Oss^®, and Blue Bone^® (n = 24) during a 12-week experimental period. Bone formation was evaluated through osteonectin and osteopontin expression. At the ultrastructural level, internalization of the biomaterial and close association with the endoplasmic reticulum (ER) and mitochondria were observed. TEM analysis also revealed no harmful effects on the cells, such as apoptotic or necrotic bodies or cell lysis. These findings indicate that the nano-HA/β-TCP composite demonstrates in vitro biocompatibility and interacts appropriately with BM-MSCs, including incorporation into the cell cytoplasm. In vivo, the Blue Bone^® group exhibited superior bone formation when compared with the other groups. Full article

Polyetheretherketone (PEEK) has emerged as a promising biomaterial for orthopedic and craniofacial implants due to its favorable mechanical properties and fatigue resistance; however, its inherent chemical inertness limits effective osseointegration. In this study, femtosecond laser surface modification is explored as a strategy to enhance the bioactivity of PEEK. Based on a previously performed parametric study, controlled micro- and nanoscale surface textures were fabricated using femtosecond laser processing, enabling precise tuning of surface roughness and wettability without the need for additional chemical treatment. The modified surfaces were systematically characterized in terms of morphology, composition, and topography using scanning electron microscopy (SEM), 3D profilometry, and water contact angle measurements. Four optimized femtosecond laser-generated surface architectures were selected for the present investigation and comprehensively characterized, followed by in vitro evaluation of dental pulp stem cell adhesion, morphology, and proliferation. The results indicate that laser-induced micro/nanostructuring enhances the surface properties of PEEK, while supporting cellular attachment and favorable cell–surface interaction. Differences in the biological response were observed among the optimized laser-textured surfaces. These findings highlight the feasibility of femtosecond laser texturing as a clean, reproducible, and scalable approach for the development of next-generation, personalized orthopedic implants. Full article

Hyaluronic acid (HA) is a glycosaminoglycan that is found within the body and has both structural and signaling functions in the extracellular matrix. HA is biocompatible and biodegradable; it has a high water content and binds directly to certain cell-surface proteins. Due to these characteristics, it is considered a promising component for the design of biomaterials for regenerative wound healing. This review covers the most recent findings on the use of HA-based biomaterials in soft tissue repair, while also incorporating earlier, foundational studies relevant to the field, focusing on HA’s characteristics, cellular interactions, design, and preclinical and clinical results. The physicochemical characteristics of HA and their influence on cellular responses and tissue regeneration are discussed to show how material properties can be adjusted for specific therapeutic purposes. There have been great advances in chemically modified composite scaffolds and HA matrices, which offer better mechanical stability and controlled degradation. At the same time, new delivery systems have been built using HA, from nanoparticles to gene delivery platforms and growth factors, and these have given the material an active role as a therapeutic agent rather than just a passive one. This narrative review covers the clinical evidence for the effectiveness of commercial products for acute and diabetic wounds, as well as burns and chronic wounds, and discusses where their use is indicated. In the end, the current limitations of the research and future applications and directions are discussed. Full article

Fungal infection remains a significant therapeutic concern owing to the scarcity of drugs, resistance development, and high levels of toxicity of many conventional antifungals. In this regard, chitosan is one such natural polymer whose biocompatibility, biodegradability, and antimicrobial nature have made it the focus of scientific interest. However, the main problem lies in the polymer’s limited aqueous solubility under physiological conditions and its poor efficacy against fungi. Thus, quaternary ammonium functionalization represents a convenient approach to solving the problem by introducing permanent positive charges into the molecular structure of chitosan, thereby improving water solubility, enabling membrane interactions, and conferring broad-spectrum antifungal activity. Such derivatives can exhibit strong interactions with the negatively charged surface of fungal cells, compromising membrane integrity and inhibiting biofilm formation. Apart from their antifungal activity, such compounds are also promising in local delivery systems, which include coatings, nanoparticles, hydrogels, and wound dressings. Considering their unique chemistry, such compounds appear quite promising for the development of novel antifungal biomaterials that can be adapted to different clinical and pharmaceutical needs. Overall, quaternary ammonium-modified chitosan could be considered a promising platform for the development of next-generation antifungal agents. This review offers a comprehensive discussion regarding the synthesis, mode of action, formulation advancements, safety profile, potential applications, and future directions of quaternary ammonium-functionalized chitosan derivatives as an antifungal agent, with an emphasis on artificial intelligence contributions to this area of research. Full article

The global transition away from di(2-ethylhexyl) phthalate (DEHP)-plasticized blood storage systems has raised important questions regarding platelet storage biology, transfusion performance, and recipient exposure to plasticizer-derived compounds. This systematic review evaluated platelet quality, plasticizer migration, and modeled transfusion exposure associated with DEHP-containing and DEHP-free platelet storage systems, including di(2-ethylhexyl) terephthalate (DEHT), diisononyl cyclohexane-1,2-dicarboxylate (DINCH), butyryl trihexyl citrate (BTHC), and tri(2-ethylhexyl) trimellitate (TOTM). English-language studies reporting quantitative platelet storage, migration, or exposure endpoints were identified through structured Google Scholar searches through 1 May 2025, supplemented by manual reference screening. Eligible studies were required to specify plasticizer composition and report quantitative biologic, migration, or exposure outcomes. Narrative reviews, opinion articles, and studies lacking extractable quantitative data were excluded. The risk of bias and the certainty of the evidence were assessed using adapted domain- and GRADE-based frameworks for mechanistic and preclinical studies. A random-effects meta-analysis was performed for day 7 platelet pH, while the remaining endpoints were synthesized descriptively. Thirty-three studies were included, comprising experimental platelet storage studies, biomaterial migration analyses, toxicologic investigations, and exposure-modeling studies. Platelet metabolic stability, including pH, glucose consumption, lactate accumulation, and mitochondrial membrane potential, was preserved across plasticizer systems. Meta-analysis demonstrated no significant difference in pooled day 7 platelet pH between DEHP and non-DEHP systems (mean difference +0.025; 95% confidence interval −0.081 to +0.131). Platelet aggregation and agonist-induced activation responses were maintained in DEHP-free systems. Selected activation and apoptotic markers, including CD62P expression and Annexin V binding, were reduced in fully DEHP-free systems, suggesting decreased storage-related membrane stress. Migration studies consistently demonstrated substantially greater DEHP leaching than DINCH and DEHT, resulting in higher modeled cumulative transfusion exposure, particularly among pediatric and neonatal recipients. Evidence further indicated that DEHP-containing whole-blood collection systems contribute to downstream contamination of platelet products with DEHP and mono(2-ethylhexyl) phthalate (MEHP). Interpretation is limited by heterogeneity in study design, storage platforms, assay methodologies, and the predominance of in vitro evidence. Overall, replacing DEHP with modern alternative plasticizers helps preserve transfusion-relevant platelet quality while potentially reducing plasticizer migration and modeled recipient exposure, thereby supporting the biologic and toxicologic rationale for transitioning to phthalate-free blood collection and storage systems. Full article

Skeletal muscle regeneration is essential for recovery after injury and for maintaining physical and metabolic function. This capacity declines with aging and is often impaired in chronic diseases, limiting effective repair. This review summarizes the main mechanisms that regulate muscle repair, with a focus on satellite cell activity and its interaction with inflammatory, metabolic, vascular, and fibrotic signals at the molecular and cellular level. We discuss how these processes are disrupted in aging, Duchenne muscular dystrophy, chronic obstructive pulmonary disease, diabetes, chronic kidney disease, and cancer cachexia, leading to delayed repair, reduced myogenic differentiation, and fibrosis. We also review current and emerging strategies to improve muscle regeneration, including exercise, bioactive molecules, physical stimulation, gene-based approaches, engineered biomaterials, and cell or cell-derived therapies. Across these conditions, chronic inflammation, metabolic dysfunction, and fibrotic remodeling appear to be common barriers to effective regeneration. Multi-target therapeutic approaches may offer advantages over single-pathway interventions, although clinical evidence is still limited; initial preclinical results, however, are promising. Full article