Search Results (351)

Candida albicans biofilms are a major cause of persistent infections and contribute to antifungal resistance as well as limitations in drug delivery. Targeting virulence traits such as biofilm formation and hyphal transition represents an effective strategy for controlling fungal pathogenicity without exerting strong selective pressure on planktonic growth. In this study, a library of structurally diverse benzophenone derivatives was screened to identify compounds with antibiofilm and anti-hyphal activities against azole-resistant C. albicans. Most benzophenone derivatives exhibited weak antifungal activity (MIC ≥ 200 µg/mL). However, several halogenated benzophenones markedly suppressed biofilm formation. Among them, decafluorobenzophenone at 10 µg/mL displayed the strongest inhibition, reducing biofilm formation to approximately 1–2% of control levels while maintaining substantial planktonic cell viability. Microscopy confirmed hyphal suppression, while qRT-PCR showed a 36-fold reduction in ALS3 expression. These findings indicate that multi-halogenated benzophenones act primarily as anti-virulence agents targeting biofilm formation and hyphal development. Molecular docking suggested a possible interaction of decafluorobenzophenone with the Als3 binding pocket. Decafluorobenzophenone showed low toxicity, with unaffected Caenorhabditis elegans viability at 10 µg/mL, plant germination at 100 µg/mL, and only slight hemolysis at 100 µg/mL. The results highlight halogen substitution as a key structural determinant and identify benzophenone scaffolds as promising leads for developing novel antibiofilm strategies against azole-resistant Candida infections. Full article

Tendinopathies represent a major clinical challenge. Vasculature, neuromuscular junctions, low cellularity, and slow extracellular matrix (ECM) turnover restrict endogenous repair and predispose injured tendons to fibrosis, mechanical weakness, and reinjury. Current therapeutic strategies including rehabilitation protocols, anti-inflammatory medications, platelet-rich plasma (PRP) injections, and surgical repair primarily address symptoms or structural deficits without correcting the underlying biological limitations of tendon healing. Cell-based therapies have emerged as a promising regenerative approach aimed at restoring tissue homeostasis through modulation of angiogenesis, collagen synthesis, immune responses, and tenogenic differentiation. Mesenchymal stem cells (MSCs), adipose-derived stem cells (ADSCs), tendon-derived stem cells (TDSCs), induced pluripotent stem cells (iPSCs), differentiated tenocytes, and extracellular vesicle (EV)-based products have demonstrated the ability to enhance vascularization, promote type I collagen remodeling, suppress excessive inflammation, and stimulate tenocyte lineage commitment. These effects are mediated through paracrine signaling, growth factor secretion, and activation of key pathways, including HIF-1α, TGF-β/SMAD, NF-κB, and PI3K/Akt signaling. Despite promising preclinical data, significant translational challenges remain, including limited cell survival at the injury site, variability in cell sources and dosing, immunogenicity, risk of misdifferentiation, and lack of standardization across clinical protocols. Emerging strategies such as genetic modification, hypoxic preconditioning, scaffold-based delivery systems, and extracellular vesicle engineering aim to enhance therapeutic efficacy and reproducibility. This review synthesizes current evidence on cell-based tendon repair, critically evaluates mechanistic insights, clinical trials, and translational barriers, and outlines future directions toward biologically informed regenerative therapies. Full article

The persistent shortage of donor organs and the inherent drawbacks of autologous grafts highlight the urgent need for advanced biomaterial scaffolds in regenerative medicine. Synthetic polymers and animal-derived matrices offer structural support, yet they frequently lack the biological complexity of native tissue or carry translational liabilities—xenogeneic antigens, pathogen transmission risk, and batch variability. This review positions the human placenta as a compelling, ethically sourced, and abundant reservoir for fully human, xeno-free biomaterials. We examine the placenta’s distinct anatomical compartments and their rich complement of extracellular matrix (ECM) proteins, growth factors, and bioactive cytokines. These components confer potent pro-angiogenic, anti-inflammatory, antimicrobial, and immunomodulatory properties, enabling precise direction of cellular behavior and tissue regeneration. We systematically assess recent advances in decellularization and the processing strategies required to preserve these bioactivities while eliminating immunogenic material. By integrating current tissue engineering applications with the regulatory and ethical frameworks shaping clinical translation, we argue that placenta-derived matrices are uniquely positioned to transcend the limitations of conventional scaffolds and serve as a robust platform for future regenerative therapies. Full article

Acute and chronic wounds remain a major clinical burden, motivating the design of multilayer biomedical composite systems capable of combining structural support, antimicrobial protection, and controlled release of therapeutic agents within a single device. These architectures integrate natural and synthetic biomaterials, hydrogels, electrospun membranes, bioactive nanoparticles, and 3D-printed scaffolds to reproduce the multifunctionality of the native extracellular matrix. This review examines how layer-by-layer design and biomaterial selection govern mechanical strength, as well as bioactivity, and how these parameters can be tuned to the distinct phases of wound repair. Particular emphasis is placed on strategies for incorporating growth factors, antimicrobial agents, metal/metal-oxide nanoparticles to enhance re-epithelialization, angiogenesis, and infection control; emerging gene-based delivery strategies are also discussed. The main technologies and biomaterial combinations reported to date are compared, alongside a critical overview of their in vitro and in vivo performance. Reproducibility, scalability, and regulatory standardization remain the main barriers to clinical translation. We conclude by outlining priority research directions to advance multilayer composites from bench-scale prototypes toward approved wound-care products. Full article

The paradigm of craniomaxillofacial (CMF) reconstruction is shifting from traditional bone grafting and biochemical adjuncts toward a nucleomechanical framework that leverages the cell nucleus as a mechanosensitive organelle. By utilizing computer-aided design and computer-aided manufacturing (CAD/CAM)-derived scaffolds with 10 µm micropillar arrays and specific interfacial stiffness (25–40 kPa), surgeons can physically manipulate the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex to achieve a nuclear aspect ratio above 2.5. This structural deformation mechanically expands nuclear pores to trigger cytoskeletal and molecular responses, such as Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) translocation. Resultantly, this physical tension pulls open chromatin fibers to activate master osteogenic regulators like RUNX2, effectively bypassing the risks and limitations associated with supraphysiologic growth factor delivery (e.g., rhBMP-2). Clinically, translating these principles involves moving away from absolute rigid internal fixation toward advanced resorbable biomaterials that permit controlled micro-motions (100–200 µm) under functional masticatory loads. This review provides a structured synthesis of the field, outlining deterministic topographic criteria, clinical boundary conditions, and the potential strategies needed to overcome age-related mechanosensory blockades. Ultimately, we establish a multidisciplinary framework that bridges precision bioengineering with native oral and maxillofacial surgical realities to drive living, biophysically mediated bone repair. Full article

Drug resistance arising during cancer development and progression remains a major challenge in the treatment of epidermal growth factor receptor (EGFR)-driven tumors, particularly those harboring the clinically relevant T790M/L858R double mutation. In this study, we developed an integrated computational workflow combining explainable machine learning, virtual screening, molecular dynamics simulations, and binding free-energy calculations to identify novel inhibitors of this drug-resistant EGFR variant. An XGBoost regression model was trained using scaffold-aware cross-validation, Bayesian hyperparameter optimization, and sequential feature selection, resulting in a compact model based on 16 molecular descriptors. The model demonstrated robust predictive performance on external validation data, while SHAP analysis identified descriptors related to the local electronic environment, fragment distribution, and molecular topology as the primary contributors to activity prediction. The optimized model was subsequently applied to screen compounds from the Enamine REAL database. Top-ranked candidates were evaluated using explicit-solvent molecular dynamics simulations and MM/GBSA binding free-energy calculations. Several compounds formed stable protein–ligand complexes and maintained key interactions with residues known to be important for EGFR inhibition, including Lys745, Met790, and Leu718. These results demonstrate that the proposed workflow can efficiently prioritize computational candidates of drug-resistant EGFR mutants and may support the development of new therapeutic strategies for overcoming resistance in EGFR-driven cancers. Full article

The European Pathfinder THOR project envisages the creation of a vascularized fragment of tissue that can be implanted in a patient using regenerated silk fibers as its building blocks. The selection of regenerated silk as the main building block of the scaffold relies heavily on its outstanding biocompatibility in comparison with either other artificial polymeric fibers or even natural silk fibers. Additionally, regenerated fibers produced through the Dynamic Dope Destabilization Spinning (D3S^TM) process are shown to exhibit high mechanical performance as reflected in values of strain at breaking and work to fracture comparable to those of the natural material. It is further shown that these fibers are endowed with the unique property of self-adhesion whereby hydrated fibers attach to one another and may sustain detachment forces of up to a few tens of MPa, a property that facilitates the generation of the scaffold with the fibers as its basic building block. Lastly, regenerated silk fibers are shown to be efficiently decorated with either peptides or small proteins, such as the vascular endothelial growth factor (VEGF), or with antibodies. The performance of both non-functionalized and decorated silk fibers is assessed in two different in vitro biological systems: (1) endothelial cell cultures, and (2) organotypic brain slice cultures. Together, these results support the use of regenerated silk fibers as versatile building blocks for biofunctional tissue scaffolds and provide experimental validation of the tissue engineering strategy established by the THOR project. Full article

Three-dimensional (3D) bioprinting has emerged as a versatile biofabrication strategy that enables the precise, spatiotemporally controlled co-deposition of living cells, biomaterials, and bioactive agents, including growth factors, cytokines, and extracellular matrix (ECM) components, into geometrically defined 3D constructs. By translating digital design models derived from computed tomography (CT), magnetic resonance imaging (MRI), or computational modeling directly into physical tissue architectures, 3D bioprinting facilitates the assembly of hierarchically organized constructs that closely recapitulate the structural, mechanical, and functional characteristics of native tissues. The principal 3D bioprinting strategies are broadly classified into scaffold-based and scaffold-free approaches. Engineered bioinks, whether formulated as cell-laden natural, synthetic, or composite polymer hydrogels, tissue-derived decellularized ECM (dECM) components, or pure cellular spheroids and organoids, constitute the cornerstone of these biofabrication platforms. Scaffold-based 3D bioprinting comprises extrusion-based, droplet-based (inkjet and drop-on-demand), light-based vat photopolymerization (stereolithography and digital light processing), and laser-assisted bioprinting based on laser-induced forward transfer (LIFT). Each of these modalities imposes distinct constraints on bioink rheology, crosslinking mechanisms, spatial resolution, throughput, and post-printing cell viability; consequently, a specific 3D bioprinting strategy is selected according to the specific requirements of the target tissue application. Scaffold-free 3D bioprinting and bioassembly techniques, including the Kenzan method, aspiration-assisted bioprinting, magnetic bioprinting, and other field-directed tissue assembly approaches, enable the fabrication of spheroid- and organoid-based constructs without the necessity for exogenous biomaterial scaffolds. Because native tissues exhibit diversity in cellular composition, ECM architecture, mechanical properties, and physiological function, no individual bioprinting platform or bioink formulation serves as a universal 3D bioprinting solution. The engineering of biomimetic tissue constructs, therefore, requires the selection of application-tailored fabrication approaches. Under this biofabrication paradigm, 3D bioprinting has been applied across a wide range of tissue engineering targets, including skin, bone, cartilage, osteochondral interfaces, cardiac and vascular tissue, neural structures, ocular, dental, and adipose tissue. This review discusses recent advances in scaffold-based and scaffold-free 3D bioprinting applications for tissue engineering and regenerative medicine across diverse tissue systems. Full article

Polydimethylsiloxane (PDMS) is a promising material for the fabrication of 3D scaffolds, thanks to its versatility and the possibility of producing sponge-like architectures through sugar-templating methods. The incorporation of functional additives further expands their potential, extending the applicability of PDMS-based systems toward advanced functional systems in areas such as environmental remediation, sensing, and biomedicine. Among these additives, metal-based nanomaterials such as layered double hydroxides (LDH) are particularly attractive due to their tuneable composition and multifunctional properties. LDHs have gained increasing attention in a range of fields, including biomedical and environmental research, thanks to their biocompatibility, controlled intercalated species release, catalysis, and sensing potential. Previous studies have incorporated LDHs into PDMS sponges via post-synthesis impregnation of pre-formed LDH crystallites, typically synthesized by co-precipitation. While widely used, co-precipitation may limit control over LDH crystallinity, morphology, and structure, affecting performance. In contrast, in situ growth strategies enable more controlled nucleation and development of the LDH structure, leading to improved structural definition and physicochemical properties. In this study, we propose a simple and cost-effective approach based on the incorporation of LDH synthesized under controlled in situ conditions into a porous PDMS sponge matrix with various architectures developed through the use of different sugar templates, enabling tuneable pore sizes while maintaining a scalable and accessible fabrication process. Full article

Calcium signaling is a fundamental regulator of cell physiology, controlling proliferation, differentiation, migration, metabolism, gene expression, and cell death. In cancer, these signaling pathways are extensively remodeled to generate spatially and temporally restricted Ca²⁺ signals that support malignant progression while avoiding calcium-induced cytotoxicity. PMCAs traditionally regarded as high-affinity calcium extrusion pumps, have recently emerged as multifunctional regulators of compartmentalized calcium signaling. In addition to maintaining low cytosolic Ca²⁺ concentrations, PMCA isoforms organize specialized signaling microdomains by interacting with receptors, ion channels, scaffold proteins, and downstream signaling molecules, thereby selectively modulating calcium-dependent pathways involved in tumor growth and metastasis. Accumulating evidence demonstrates that PMCA isoforms exert distinct, context-dependent functions in cancer. PMCA1 primarily contributes to basal calcium homeostasis but has also been implicated in tumor progression, angiogenesis, and regulation of the tumor immune microenvironment. PMCA2 promotes survival and oncogenic signaling in HER2-positive breast cancer through stabilization of receptor signaling complexes. PMCA3 has been linked mainly to endocrine tumors and selected malignancies, although mechanistic evidence remains limited. PMCA4 exhibits the greatest functional diversity, acting either as a tumor suppressor or a promoter depending on the cancer type by regulating localized calcium signaling, cell migration, invasion, differentiation, and interactions with oncogenic signaling networks. This review summarizes current advances in the structural biology, regulation, and signaling functions of PMCA isoforms, with particular emphasis on their emerging roles in cancer biology. We also discuss the potential of PMCAs as prognostic biomarkers and therapeutic targets, highlighting the importance of isoform-specific strategies for targeting calcium signaling in cancer. Full article

Bone regeneration remains a significant clinical challenge, particularly for large or critical-sized defects caused by trauma, disease, or congenital abnormalities. Mesenchymal stem cells (MSCs) have emerged as a promising cell source for bone tissue engineering, with their osteogenic differentiation playing a crucial role in bone repair. Biomaterials serve as scaffolds that facilitate MSC-mediated bone regeneration by providing structural support and mimicking the extracellular matrix (ECM). This review explores recent advancements in biomaterials designed to promote MSC osteogenesis through two primary approaches: biochemical and physicomechanical stimuli. Therapeutic agent-loaded scaffolds, incorporating growth factors, small molecules, gene materials, peptides, proteins, and extracellular vesicles (EVs), have been extensively studied for their ability to enhance osteogenic differentiation. However, concerns regarding toxicity, off-target effects, and regulatory limitations have led to increasing interest in biomaterials that utilize physicomechanical cues such as stiffness, viscoelasticity, topography, porosity, and dynamic forces (shear stress, compression, vibration) as alternative or complementary strategies. Furthermore, the synergistic effects of multiple physicomechanical cues are being explored to regulate MSC behavior for promoting bone regeneration. This review discusses current challenges, emerging trends, and future directions in the development of next-generation biomaterials that integrate biochemical and physicomechanical approaches for clinical applications in bone repair and regeneration. Full article

Fascia serves as both a mechanical scaffold and a progenitor cell reservoir critical for wound healing and tissue regeneration. This study developed an In Situ Induced Fascial Analogue (iFA) via low-growth-factor Matrigel injection into mouse subcutaneous fascia, using silicone as a control. At 14 days, histological and ultrastructural analyses showed that the iFA possessed an organized collagen architecture comparable to native fascia, distinct from the dense fibrous capsules in controls. qPCR and immunofluorescence revealed a pro-reparative macrophage-associated microenvironment characterized by increased CD206 expression and demonstrated the enrichment of CD34⁺/PDGFRα⁺ co-expressing telocytes (TCs) within the iFA, consistent with their characteristic molecular and ultrastructural features. Ex vivo assays demonstrated cell migratory activity, and in vivo wound healing assays showed that iFA-derived cells significantly accelerated wound closure and re-epithelialization. This study established a structurally biomimetic fascial analogue enriched with CD34⁺/PDGFRα⁺ TCs that avoids pathological fibrosis, providing a novel in situ engineering strategy for generating fascia-like tissues and a platform for future regenerative research. Full article

Ti₃C₂T_x MXene is an attractive conductive scaffold for lithium-ion battery anodes owing to its two-dimensional structure, hydrophilic surface chemistry, and tunable interlayer spacing; however, pristine MXene generally exhibits moderate lithium-storage capacity and suffers from restacking-induced loss of accessible active sites. In this study, Ti₃C₂T_x MXene@ZnO composites were prepared by growing ZnO on Ti₃C₂T_x MXene nanosheets with controlled growth times of 1, 2, and 3 h. The materials were characterized by FE-SEM, XRD, and N₂ adsorption–desorption measurements, and their electrochemical performance was evaluated in CR2032-type half-cells. Structural analyses showed that MZ-2h exhibited a more uniform distribution of ZnO particles, increased MXene interlayer spacing, and the highest BET surface area (42.77 m² g⁻¹) and total pore volume (0.1027 cm³ g⁻¹), whereas excessive ZnO growth for 3 h caused particle aggregation and reduced pore accessibility. Electrochemical measurements showed that MZ-2h delivered the best rate capability, maintaining 182.4 mAh g⁻¹ at 0.2 C and 48.0 mAh g⁻¹ at 5 C, together with the highest second-cycle Coulombic efficiency of 88.4%. These results demonstrate that controlling ZnO growth time is an effective strategy for balancing ZnO-derived lithium-storage contribution, particle dispersion, pore accessibility, and the MXene-based framework in Ti₃C₂T_x MXene-based hybrid anodes. Full article

Cultured meat aims to manufacture genuine animal tissue from cells in vitro, displacing the environmental and ethical liabilities of livestock slaughter. Because the final product must reproduce the fibre architecture, fat marbling, and nutrition of conventional meat, the cell—its identity, proliferative ceiling, and differentiation fidelity—is the central determinant of feasibility. This review consolidates the stem cell biology of cultured meat from a tissue engineering perspective. We first compare the principal cell sources: muscle satellite cells, which offer authentic myogenicity but limited expansion; pluripotent stem cells, which are effectively immortal but require directed differentiation; and mesenchymal, adipogenic, and fibro-adipogenic progenitors that supply fat and connective tissue. We then examine how myogenic and adipogenic commitment is controlled through growth-factor and small-molecule signalling, serum-free medium design, and co-culture strategies that recreate the multicellular composition of meat. We next survey biomaterial scaffolds—edible microcarriers, hydrogels, and decellularized plant matrices—that organize stem cells into anisotropic, perfusable, macroscale constructs, drawing on scaffold-design principles from regenerative medicine. Finally, we address bioreactor scale-up, medium cost, cell-line stability, and regulatory translation. We argue that cultured meat will advance fastest when cell source, differentiation protocol, and scaffold architecture are co-designed rather than optimized in isolation. Full article

An innovative strategy for collagen self-assembly with accelerated intra and extrafibrillar mineralisation is introduced to generate bone scaffolds with biomimetic properties. This method, termed Rapid Fibrillogenic Mineralisation (RFM), leverages coprecipitation with 10× Simulated Body Fluid (10× SBF) during fibril formation to maximise nucleation, particularly within intrafibrillar zones at molecular termini. Densification is achieved within minutes via plastic compression driven by capillary action, producing bone-like scaffold density without compromising the collagen matrix. Transmission electron microscopy confirms intrafibrillar hydroxyapatite crystals within 15 min, while X-ray diffraction demonstrates distinct HA peaks across groups. Scanning electron microscopy verified extrafibrillar mineralisation after 4 h, with saturation by 6 h, yielding ‘nanoflower’ crystal clusters. Infrared spectra showed increased carbonate content over time, indicating lattice substitutions characteristic of natural bone. Enhanced mineralisation translated into significant mechanical gains as Dynamic Mechanical Analysis revealed compressive moduli approaching cancellous bone (up to 283 ± 31 MPa). In addition, a decrease in the piezoelectric coefficient occurs with increased mineralisation process, highlighting the effects of mineral inclusions on collagen fibre composition and anisotropy. Biologically, mineralised scaffolds supported cellular growth compared to collagen controls. RFM thus enables rapid, reproducible fabrication of biomimetic bone scaffolds that closely emulate native mineralisation patterns and mechanical behaviour. Beyond offering a practical route for scaffold production in tissue engineering, the process also provides new insights into bone physiology and in vitro modelling. By reshaping collagen into a synthetic echo of nature’s bone, RFM establishes a rapid approach for designing functional biomaterials with translational potential. Full article