Search Results (10,830)

Background: Neurosurgery depends heavily on implanted biomaterials, and the endovascular treatment of intracranial aneurysms (IAs) is the paradigmatic case, since coils, flow diverters and intrasaccular devices achieve durable occlusion only through intrasaccular thrombus organization and endothelial coverage of the neck, both governed by the local flow environment. Computational fluid dynamics (CFD) resolves that environment but is too slow and too solver-dependent for clinical or device design use. Graph and geometric deep learning operates natively on the unstructured meshes in which vascular anatomy and implanted scaffolds are represented and has been proposed as the technology that would close this gap. Methods: Four databases were searched up to 29 July 2026 for original studies developing or validating graph-based or geometric deep learning applied to IA geometry, with a hemodynamic or clinical outcome. Screening and extraction were performed in duplicate; risk of bias with PROBAST and artificial intelligence signaling items, reporting with TRIPOD+AI, and synthesis followed SWiM. Results: Twelve studies (2021 to 2026) were included: seven clinical (1965 aneurysms, plus 81 externally) and five computational (up to 984 geometries). Learned geometric representations discriminated rupture, growth and post-embolization recanalization better than morphological indices and then PHASES, reaching an area under the curve of 0.795 to 0.97 internally. Graph and point cloud surrogates reproduced hemodynamic fields with normalized errors of 2% to 5% in seconds rather than hours, and one transformer-based graph network predicted the extent and timing of intra-aneurysmal thrombus formation over a reactive surface. External validation was reached by two studies, and clinical utility was achieved in one; discrimination fell from 0.85 to 0.71 in one external test, and surrogate error rose from 4.1% to 19.1% on patient-derived anatomy. No model was trained on a device-laden geometry. Additionally, 5/7 clinical studies classified cross-sectional rupture status rather than prospectively predicting future rupture. Conclusions: Graph and geometric deep learning has substantially reduced the computational burden of hemodynamic analysis, but reliable generalization to unseen patient-specific anatomy remains a relevant challenge. Shared patient-specific benchmarks, prespecified external validation, reporting of calibration, and extension of training corpora to implanted anatomy are necessary next steps towards virtual evaluation of neurovascular biomaterials. Full article

This study evaluated the osteogenic differentiation and paracrine response of dental pulp stem cells (DPSCs) cultured within a 3D-printed alginate/chitosan/cannabidiol (CBD) hydrogel. DPSCs from a single donor (passage 6; n = 3 technical replicates per condition) were cultured as monolayers or on hydrogel constructs (CBD 0–12 mg/mL) in basal or osteogenic medium for 7, 14, and 21 days. Alizarin Red S staining confirmed retention of osteogenic competence. Supernatant osteoprotegerin (OPG) and RANKL were quantified by Luminex immunoassay. Monolayer cultures produced up to 7867.5 ± 676.8 pg/mL OPG, whereas hydrogel cultures yielded 9.7–69.3 pg/mL (98–99.8% reduction; p < 0.001). RANKL remained stable at 9–11 pg/mL across all conditions; neither analyte varied with CBD concentration. The OPG/RANKL ratio collapsed from 215–858 to 1.0–6.3 in hydrogel groups. Since RANKL—co-secreted by the same cells—was unaffected, a generalized cellular or secretory deficit is unlikely to explain the selective OPG decrease. The data are consistent with charge-selective retention of cationic OPG (pI ≈ 8.5–9.0) within the anionic alginate network, although this mechanism remains hypothetical pending direct adsorption and ζ-potential verification. These findings indicate that scaffold fixed charge constitutes an active variable in the apparent secretome of three-dimensional cultures. Full article

Background/Objectives: Epidural electrical stimulation (EES) is an investigational, off-label neuromodulation strategy used adjunctively with rehabilitation in chronic spinal cord injury (SCI), but safety and longitudinal functional data specific to traumatic cervical SCI remain limited. This is a descriptive safety-and-feasibility study, not an efficacy study; no efficacy or causal claim is made. Methods: In this single-centre observational cohort, 32 consecutive patients with traumatic cervical SCI underwent EES implantation and were included in baseline and safety analyses, while longitudinal analyses comprised the 26 participants with complete Spinal Cord Independence Measure (SCIM) III data at baseline and 3, 6, 9 and 12 months. Rehabilitation dose was quantified (approximately 1087 prescribed therapy hours over 12 months) and adverse events were classified using ISO 14155:2020 definitions with WHO–UMC causality grading. Prespecified outcomes were device- and procedure-related adverse events and total and domain-specific SCIM III scores; analyses were descriptive. Results: Patients were aged 33.8 ± 10.3 years, 28 (87.5%) were male, and baseline AIS grade was A in 31 and B in 1. Mean total SCIM III increased from 14.81 ± 8.92 at baseline to 21.77 ± 14.60, 25.12 ± 15.90, 28.23 ± 17.68 and 32.42 ± 19.45 at 3, 6, 9 and 12 months (all p < 0.001), with gains across self-care, respiration and sphincter management, and mobility; 10 of 32 patients (31.3%) improved by at least one AIS grade. Adverse events were infrequent: sterile hardware-site inflammation (2, 6.3%), explantation (1, 3.1%) and a first-ever seizure (1, 3.1%), without stimulation-related neurological deterioration. Conclusions: The cohort was highly selected (31/32 baseline AIS A; 87.5% male; injury-to-implant interval 10–339 months), no comparator group was available, stimulation programming was individualised rather than protocolised, and 6 of 32 patients lacked complete 12-month follow-up; these features limit reproducibility and generalisability and preclude any inference about effectiveness. EES with rehabilitation was well tolerated and accompanied by progressive functional gains, although the uncontrolled design precludes causal inference. The contribution of this report is therefore transparent safety, dose and programming data, together with a prespecified protocol framework intended to make a controlled, propensity-matched evaluation of EES in traumatic cervical SCI feasible and reproducible. Full article

Polycaprolactone (PCL) is a widely used biodegradable polyester in tissue engineering, drug delivery, and temporary implant design. While its favorable processability, biocompatibility, and low melting temperature are highly advantageous, its slow and condition-dependent degradation remains a major limitation for precise temporal control in biomedical applications. Despite extensive literature on PCL, a critical knowledge gap remains in linking fundamental molecular chain scission directly to macroscopic structural evolution, mechanical failure, and predictable in vivo device performance. To address this, this review provides a comprehensive synthesis of PCL degradation mechanisms, with a particular emphasis on PCL-bioceramic composites designed for hard tissue engineering. We elucidate the progressive degradation pathway—distinguishing between initial hydrolytic chain scission, oligomer formation, the generation of low-molecular-weight degradation products, and their subsequent metabolic fate under physiological conditions. Furthermore, this review critically evaluates how fundamental variables—specifically molecular weight, crystallinity, bioceramic fillers, device geometry, and physiological environments—alter degradation kinetics. By connecting molecular weight reduction to subsequent mass loss, thermal behavior, and mechanical deterioration, we establish a framework for understanding how structural reorganization and crystallinity evolution govern material failure. This review bridges the gap between simplified in vitro models and complex in vivo realities, supporting the rational design of composite biomedical devices with tailored, predictable resorption profiles. Full article

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

Medicinal plants are major sources of therapeutic natural products, yet the cell-type-specific organization that governs metabolite biosynthesis, transport, and storage remains imperfectly resolved by organ-level omics. This review synthesizes studies published up to June 2026 that used single-cell, single-nucleus, spatial, metabolomic, and epigenomic approaches to medicinal plant systems, following a PRISMA-guided literature search across PubMed, Web of Science, Scopus, and CNKI. Emerging evidence shows that specialized metabolism is organized through discrete and often rare cell populations, including idioblasts, laticifers, glandular trichomes, secretory epidermal cells, internal phloem-associated parenchyma, cork and periderm cells, mesophyll cells, and other biosynthetic niches. Single-cell RNA sequencing has defined these populations and reconstructed developmental trajectories, whereas single-cell metabolomics and mass spectrometry imaging reveal that metabolite accumulation frequently diverges from biosynthetic gene expression because of intercellular transport, storage capacity, and subcellular compartmentation. Single-cell ATAC-seq and multiome profiling further identify cell-type-specific regulatory regions, transcription factors, and candidate promoters controlling metabolic competence. Together, these technologies are reshaping medicinal plant biology from pathway-centric catalogs into spatially and developmentally resolved cellular maps. We highlight how artificial intelligence (AI)-assisted integration can accelerate cell annotation, regulatory network inference, metabolite assignment, and prioritization of biosynthetic genes, transporters, and engineering targets. Future progress will depend on comparative medicinal plant atlases, improved recovery of recalcitrant tissues, matched transcriptomic, metabolomic, and spatial designs, and functional validation of cell-type-specific mechanisms. Full article

Biological adhesion systems represent some of the most structurally and functionally versatile interfacial solutions in nature, enabling organisms to attach, locomote, and manipulate surfaces across environments ranging from dry rock faces to turbulent marine substrates. This review surveys the structural and mechanistic diversity of biological adhesion, organizing known systems into two principal categories: dry and wet adhesion. Dry adhesion, exemplified by geckos, spiders, and beetles, relies primarily on physical contact forces, most notably van der Waals interactions, arising from hierarchical micro- and nanoscale surface architectures that maximize real contact area without the use of adhesive secretions. Wet adhesion, as demonstrated by marine mussels, octopuses, and tree frogs, operates through biochemical crosslinking, negative-pressure suction, and fluid-displacement mechanisms that act specifically at aqueous or fluid-saturated interfaces. The engineering relevance of these systems is substantial: bioinspired adhesives derived from gecko-like hierarchical fibrillar surfaces have found application in climbing robots, transfer printing, and reversible electronic attachment; mussel-inspired catechol chemistry has enabled a generation of underwater sealants and surgical tissue adhesives; and octopus- and remora-inspired suction technologies inform the design of soft robotic grippers and marine sensor platforms. Despite significant advances, challenges remain in scalable fabrication, contamination resistance, and translating organism-level performance to engineered systems at commercially viable scales. This manuscript reviews each biological model with respect to its structural form, functional mechanism, adhesion classification, documented engineering applications, and inherent limitations, concluding with a synthesis of future research directions critical to advancing the field of bioinspired adhesive materials and systems. Full article

Background/Objectives: Alginate hydrogels are widely used in tissue engineering; however, their reported properties vary significantly due to differences in formulations and processing conditions, which limits direct comparison across studies. This study aims to systematically evaluate the relative and combined effects of alginate viscosity grade, polymer concentration, and CaCl₂ crosslinking concentration on hydrogel structural, mechanical, and biological behaviour. Methods: Hydrogels were prepared using three commercially available alginates of low, medium, and high viscosity. Polymer concentration (0.5–2% w/v) and CaCl₂ concentration (2.5–10% w/v) were systematically varied under controlled fabrication conditions. Morphology was analysed using scanning electron microscopy, swelling and water uptake were quantified, mechanical properties were assessed via dynamic mechanical analysis, and cell viability was evaluated using Chinese hamster ovary (CHO) cells encapsulation over 20 days. Statistical analysis was performed using two-way ANOVA. Results: Hydrogel properties were governed by non-linear interactions between formulation parameters. CaCl₂ concentration was identified as the dominant factor influencing structural and biological outcomes, with increasing crosslinking concentration reducing pore size, swelling, and water uptake, and decreasing cell viability by up to ~60%. In contrast, polymer concentration and alginate viscosity grade primarily controlled mechanical behaviour, with increased polymer content and viscosity resulting in higher storage and Young’s moduli. Significant interaction effects confirmed that hydrogel properties are not independently tunable but depend on the combined influence of all parameters. Conclusions: Crosslinking concentration dominates structural and biological responses in alginate hydrogels, while polymer parameters modulate mechanical properties within this constraint. These findings establish a formulation-dependent trade-off between mechanical stiffness and cytocompatibility, providing a comparative framework for rational selection of alginate systems based on application-specific requirements. 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

Short bowel syndrome is a rare and clinically heterogeneous condition resulting from extensive intestinal resections or functional impairment, leading to malabsorption, fluid and electrolyte losses, and potential progression to intestinal failure requiring long-term parenteral nutrition. The long-term outcome of SBS is largely determined by intestinal adaptation, a progressive physiological response involving epithelial remodeling, intestinal stem cell expansion, lineage-specific proliferation, vascular remodeling, and the activity of trophic mediators—most notably glucagon-like peptide-2 (GLP-2)—whose clinical relevance is exemplified by teduglutide. Despite significant therapeutic advances, the mechanisms underlying adaptation remain incompletely understood, and preclinical models are essential tools for addressing this gap. In vitro systems—including Caco-2 epithelial cultures, intestinal organoids and enteroids, and tissue-engineered intestinal constructs—enable pathway-specific mechanistic investigation and hold promise as regenerative platforms. Murine surgical models of small bowel resection and ileocecal resection provide an integrated in vivo context for dissecting cellular and molecular mechanisms of adaptation. Large animal models, particularly minipig platforms, offer anatomical and physiological proximity to humans required for translational and therapeutic evaluation. In this narrative review, we provide an updated overview of these preclinical systems, critically examining their respective strengths, limitations, and translational relevance to advance the understanding of intestinal adaptation and inform the development of more effective therapeutic strategies for SBS (graphical abstract). Full article

Cleft palate is a congenital anomaly that causes functional and esthetic challenges, and the hard palate is essential for feeding, speech, and separation of the oral and nasal cavities. Yet, current reconstructive techniques do not restore its bony component. Building on previous in vitro work showing that decellularized palatal mucoperiosteum, microperforated with Quantum Molecular Resonance (QMR^®) technology and recellularized with mesenchymal stem cells, preserves the collagen microenvironment, supports engraftment, and shows osteoinductive potential, this study evaluated the early feasibility and regenerative potential of bioengineered mucoperiosteal scaffolds (BEMS) in Landrace pigs model. Bone marrow was collected from recipient pigs to isolate pBM-MSCs. Donor palatal mucoperiosteum was decellularized, microperforated, and recellularized with these cells to generate BEMS. After surgical creation of a cleft palate, four pigs received BEMS, and two controls underwent standard palatoplasty. At one month, scaffold-treated animals showed early mucosal and osseous regeneration, including neo-epithelium, connective tissue, and new bone formation, without clinical or routine histological signs of acute rejection. SPARC (Secreted protein acidic and rich in cysteine) expression supported osteogenic activity. Regenerated palates were stable and fracture-resistant, whereas controls showed incomplete repair and fractures. These findings suggest that BEMS may address limitations of conventional palatal reconstruction and support further investigation for human palatal bone regeneration. Full article

Periodontal regeneration requires the reconstruction of root cementum, periodontal ligament, and alveolar bone, which are frequently disrupted by periodontitis, trauma, and other inflammatory conditions. Although periodontal ligament stem cells (PDLSCs) have been considered promising for periodontal tissue engineering because of their multipotency, self-renewal capacity, and immunomodulatory activity, direct cell-based therapy still faces various limitations, including donor variability, culture-related changes, delivery difficulties, and safety concerns. Exosomes and small extracellular vesicles derived from PDLSCs have therefore attracted attention as potential cell-free mediators of PDLSC paracrine activity. PDLSC-derived exosomes carry bioactive molecules, including proteins, lipids, messenger RNAs, and microRNAs, and can influence recipient cell behavior in periodontal and bone regenerative environments. In vitro and preclinical animal studies indicate that PDLSC-derived exosomes are involved in osteogenesis, periodontal attachment repair, cementogenesis, angiogenesis, mechanotransduction, cell proliferation/survival, and immune regulation. Their biological effects are closely related to the condition of their parental PDLSCs, their cargo, and the exosome isolation and characterization methods used. In this review, we summarize recent findings on the isolation strategies used, biological functions of, and therapeutic potential of PDLSC-derived exosomes, with particular focus on protein cargo, proteomic signatures, proteoform-related interpretation, and microRNA-mediated regulation. We also discuss current challenges in exosome isolation, characterization, delivery, stability, and reporting standards for future periodontal regenerative applications. The findings discussed throughout are preclinical, and their translation to clinical settings remains to be explored. Full article

The deep sea harbors a substantial proportion of the ocean’s unexplored biological and chemical diversity, while hydrothermal vent ecosystems expose resident organisms to unusual combinations of hydrostatic pressure, steep chemical gradients, reduced compounds, and elevated metal concentrations. This Review examines the deep-sea vent mussel Bathymodiolus azoricus, a dominant species at Mid-Atlantic Ridge hydrothermal fields, as a source of biological mechanisms and molecular systems with potential biomedical relevance. We integrate three areas that have largely developed separately in the literature: innate immunity and host–symbiont interactions, mussel-derived wet adhesion and byssal structural proteins, and shell biomineralization and repair. These published observations are complemented by targeted reanalyses of legacy and more recent B. azoricus transcriptomic resources, used here as supporting transcriptomic evidence for molecular families relevant to these themes rather than as standalone genome-scale transcriptomic studies. Particular attention is given to mussel foot proteins and byssal collagens as candidate templates for wet-tissue adhesives and structural biomaterials, and to shell-derived calcium carbonate as a potential precursor for calcium-phosphate-based materials. We further advance a specific, testable hypothesis—long-term exposure to the metal-rich hydrothermal vent environment may have influenced the metal-binding chemistry of B. azoricus adhesive and structural proteins, potentially generating functional properties distinct from those of shallow-water mytilids. This possibility is biologically plausible in light of established DOPA–metal coordination mechanisms in mussel adhesion, but no direct comparative measurements of Fe³⁺-binding affinity, metal-mediated cross-linking, or adhesive performance currently demonstrate such an advantage in B. azoricus. The species should therefore be regarded not as a proven source of superior vent-adapted biomaterials, but as a well-suited experimental system in which immunity, bioadhesion, biomineralization, and environmental adaptation converge to generate specific hypotheses for biomedical discovery. Comparative functional studies, protein-level validation of transcript-derived candidates, and improved molecular characterization of foot and mantle tissues will be required to test these possibilities. Full article

Urethral reconstruction is required for a variety of congenital and acquired conditions. Current grafting techniques rely on autologous tissues such as buccal mucosa, which are often limited by donor-site morbidity. Biomaterials could be an alternative. However, they may present immunological risks and inconsistent surgical outcomes. The tissue-engineering self-assembly approach, which uses autologous patient cells to generate tissue constructs without exogenous biomaterials, offers a promising alternative by improving graft integration. Such natural tissue-engineered constructs exhibit promising histological similarity to native urethral tissue and hold potential for clinical application. However, graft selection for surgery remains subjective, lacking standardized mechanical criteria to ensure consistent quality. Previous efforts to quantify graft properties through uniaxial tensile testing have proven informative but require cutting the tissue into standardized specimens and are therefore not readily suited to routine quality-control workflows. To address this, we investigated puncture testing as a simpler practical alternative that does not require tissue cutting and assessed its correlation with tensile testing and surgeon-based evaluation. Self-assembled dermal and urethral constructs were evaluated using uniaxial tensile and puncture tests, and results were correlated with the surgeon’s qualitative assessments during graft handling. Our findings reveal a strong linear relationship between two mechanical testing techniques. Puncture testing also showed a strong relationship with surgeon-based qualitative assessments of graft handling. This study highlights the potential of puncture testing as a practical mechanical assessment tool for characterizing graft mechanical behavior in the context of surgical handling, and offers a pathway toward the development of standardized, objective quality control protocols for tissue-engineered urethral grafts prior to implantation. Full article

Diabetic foot ulcers (DFU) are among the most severe complications of diabetes, resulting from a combination of metabolic dysregulation, vascular insufficiency, neuropathy, chronic inflammation, and impaired tissue repair, whereas diabetic foot infection (DFI) may develop within this compromised wound environment and frequently involves polymicrobial communities and biofilms. This review evaluates the mechanistic and translational basis for the use of antimicrobial peptides (AMP) in DFU and DFI, with emphasis on the diabetic wound microenvironment, polymicrobial ecology, endogenous AMP dysregulation, mechanisms of action, therapeutic development, and barriers to clinical translation. Hyperglycemia, ischemia, oxidative and proteolytic stress, and impaired innate immunity sustain inflammation, delay tissue repair, and promote microbial persistence. These conditions may also complicate antibiotic treatment through impaired tissue exposure and biofilm-associated tolerance. Depending on the peptide and experimental context, AMP may provide direct antimicrobial or antibiofilm activity and may also exert immunomodulatory or pro-reparative effects involving inflammatory signaling, angiogenesis, keratinocyte and fibroblast migration, and re-epithelialization. Approaches under investigation include engineered peptides, combination regimens, and local biomaterial-based platforms, including hydrogels, dressings, scaffolds, and nanoparticle-conjugated systems. Clinical translation remains constrained by proteolytic instability, potential host-tissue toxicity, limited selectivity, limited predictive value of preclinical models, heterogeneous clinical populations, nonstandardized endpoints, and manufacturing and regulatory requirements. Preclinical evidence supports further evaluation of approaches for local delivery of AMP, whereas clinical evidence in DFU and DFI remains limited and heterogeneous, with no AMP-based intervention yet demonstrating sufficiently consistent clinical benefit to support routine use. Full article