Search Results (1,651)

Bone defects from trauma, tumour resection, infection, and degenerative disease remain a major clinical burden, and autografts face limitations of supply and donor-site morbidity. Three-dimensional (3D) printing offers a route to patient-specific, architecturally defined bone scaffolds, while biopolymers from natural sources provide biodegradability, biocompatibility, and extracellular matrix-mimicking cues consistent with sustainable, green biomaterials science. This review synthesises recent progress in 3D printing of biopolymer-based scaffolds for bone tissue engineering. We first examine the principal feedstocks—alginate, gelatin and gelatin methacryloyl, collagen, chitosan, silk fibroin, cellulose, and microbial polyesters—and their preparation, crosslinking chemistry, and printability. We then compare extrusion, light-based, and indirect printing technologies and the process–property relationships governing resolution, mechanical competence, and cell viability. Composite and functionalisation strategies, including biopolymer–bioceramic hybrids and controlled delivery of growth factors and antimicrobial agents, are analysed as routes to osteoinduction, vascularisation, and infection control. Finally, we evaluate translational performance in preclinical models and outline central challenges of vascularisation, mechanical–degradation matching, scalability, and regulatory standardisation. Biopolymer 3D printing is positioned as a ve rsatile, sustainable platform whose clinical maturation depends on integrated material, structural, and biological design. Full article

Developing functional foods that address both oxidative stress and physiological challenges like dysphagia is a critical frontier in personalized nutrition. This study investigates the multi-component synergy of Fu Ling Yin Zi (FLYZ), a traditional dietary therapy, and translates its functional properties into a 3D-printed dysphagia-friendly food. Using response surface methodology, the optimal FLYZ formulation was established at a 5:1:5 ratio of Poria cocos (Schw.) Wolf., Amygdalus communis Vas, and Citrus reticulata. Network pharmacology and molecular docking suggested that FLYZ’s active compounds (e.g., nobiletin, stigmasterol, tangeretin, l-SPD, glabridin, estrone) may mitigate oxidative stress via multiple targets (PTGS2, AKT1, TNF, ESR1, MMP9, and MAOA), with pathway analysis pointing to a potential role of the AKT1/GSK3β/HIF-1α axis. Subsequent in vitro cellular assays demonstrated that FLYZ enhanced antioxidant enzyme activities, reduced intracellular ROS, and modulated the expression of associated genes, supporting a potential link to this pathway. To actualize these functional benefits for patients with swallowing difficulties, a novel 3D-printing ink incorporating FLYZ and walnut oil within a hydrogel matrix (3% xanthan gum, 3% pectin, 1.5% carrageenan) was developed. The printed constructs exhibited excellent shape fidelity and, based on standardized IDDSI fork and spoon tests, were categorized as level 4 (pureed/extremely thick). Furthermore, a simulated in vitro digestion model showed that the colloidal network significantly protected FLYZ’s polyphenols and flavonoids, markedly improving their bioaccessibility and post-digestion antioxidant capacity. Collectively, this work establishes an integrated approach that combines predictive molecular profiling with advanced 3D food printing, thereby supporting the development of future foods tailored for personalized nutrition. Full article

Multifunctional dressings capable of maintaining a moist environment, supporting tissue regeneration, and delivering bioactive compounds are increasingly being explored as promising strategies for burn wound management. In this study, alginate-based emulgel patches incorporating hydrophilic and lipophilic plant extracts were developed by extrusion-based 3D printing as potential topical systems for burn wound applications. The formulation included sodium alginate, hyaluronic acid, and hydroglyceric extracts of Calendula officinalis, Matricaria chamomilla, and Plantago major, as well as oily extracts of Hippophae rhamnoides and Hypericum perforatum. The emulgel was evaluated for pH, rheological behaviour, spreadability, physical stability, apparent hydrodynamic size distribution, zeta potential, total polyphenol content, and antioxidant activity. Following Ca²⁺-induced crosslinking, uniform and flexible 3D-printed patches were obtained and further characterised for pharmacotechnical, physicochemical, structural, functional, and biological properties. The emulgel exhibited suitable characteristics for extrusion-based printing, while the resulting patches showed good dimensional uniformity, flexibility, swelling capacity, water vapour transmission, and surface pH compatible with topical application. FTIR, DLS, SEM, and SEM–EDX analyses supported the formation of a Ca²⁺-crosslinked alginate network and confirmed the presence of structurally heterogeneous domains with homogeneous calcium distribution. The patches retained plant-derived bioactive compounds, with a total polyphenol content of 0.2878 ± 0.016 mg GAE/g hydrated patch, and showed improved antioxidant activity compared with the corresponding emulgel. In vitro release studies indicated the time-dependent diffusion of polyphenols over 24 h, with cumulative release reaching 64.42%. The patches also exhibited a water vapour transmission rate of 1270 ± 93 g/m²/24 h, indicating adequate moisture regulation. HaCaT cell viability remained above 90% at lower tested concentrations, demonstrating a favourable biocompatibility profile. Overall, the developed 3D-printed alginate emulgel patches represent promising multifunctional systems for potential burn wound management and warrant further preclinical investigation. Full article

The extracellular matrix (ECM) provides a dynamic microenvironment that regulates cell proliferation, migration, and tissue remodeling during wound healing. However, replicating the structural and functional complexity and ECM heterogeneity of native skin ECM remains challenging with conventional single-material hydrogels. Recent advances in multimaterial 3D bioprinting have enabled the spatial integration of diverse biomaterials within a single construct. Lignocellulose has attracted increasing attention as a promising biomaterial for recreating key structural features of the native ECM because of its fibrous architecture, mechanical strength, and biocompatibility. This review offers a comprehensive and integrated perspective on the use of lignocellulose-based multimaterial printing to recreate ECM-mimicking architectures, an underexplored area at the intersection of biomaterials and biofabrication. The roles of cellulose, hemicellulose, and lignin in printability, scaffold stability, porosity, bioactivity, and wound-healing performance are discussed. Representative studies have demonstrated that lignocellulose-based multimaterial bioinks provide porous architectures that support cell adhesion, proliferation, and tissue regeneration. These benefits are accompanied by improved mechanical performance, as cellulose nanofibers exhibit elastic moduli exceeding 100 GPa, and lignin-containing hydrogels have achieved compressive moduli of up to 135 kPa. Such mechanical advantages make lignocellulosic materials particularly attractive for fabricating ECM-mimicking scaffolds that require long-term structural integrity. Finally, key design considerations and current limitations associated with lignocellulose-based multimaterial bioprinting are critically discussed. A framework for the rational design of lignocellulose-based multimaterial bioinks is presented, together with future directions toward gradient and adaptive scaffolds, smart wound dressings, and advanced wound-healing applications. Full article

Three-dimensional (3D) cell culture models more faithfully reproduce native tissue organization and function than conventional two-dimensional systems, yet many existing bioprinting methods depend on scaffolds, complex instrumentation, or limited control over cell positioning. This review examines magnetic bioinks as a versatile platform for contactless 3D cell manipulation and biofabrication. It first outlines the fundamentals of magnetophoresis and defines magnetic bioinks as combinations of magnetic agents, including magnetic nanoparticles or paramagnetic salts, with biological components such as cells, proteins, or fluids. The review then compares label-based strategies, in which cells are magnetized and guided by positive magnetophoresis, with label-free approaches that exploit magnetic susceptibility differences to position diamagnetic cells through negative magnetophoresis. Across these methods, magnetic bioinks have enabled single-cell sorting, spatial patterning, spheroid and co-culture assembly, multilayer tissue formation, and hydrogel-integrated printing. These capabilities support applications in disease modeling, drug screening, biosensing, regenerative medicine, and emerging biofabrication under microgravity conditions. The paper also highlights key limitations, including nanoparticle biocompatibility, paramagnetic salt toxicity, osmotic stress, and the need for better assay standardization and translational validation. Overall, magnetic bioinks represent a promising scaffold-free approach for rapidly producing physiologically relevant 3D biological constructs for research and clinical innovation. Full article

The synthesis of reactive sucrose derivatives is of significant interest for the development of novel biocompatible polymers. In this study, an octa-substituted sucrose derivative containing isocyanate groups was synthesized via a urethane-forming reaction carried out in an aprotic solvent at the phase interface. This approach exhibits high selectivity and provides a target product yield of up to 60%. Subsequently, using the same reaction mechanism, the isocyanate derivative was converted into an octa-functional methacrylate derivative capable of forming three-dimensional cross-linked networks. The structures of both the intermediate and final products were confirmed by IR, ¹H NMR, and mass spectrometry. The sucrose-based prepolymer was further evaluated in the formation of cross-linked structures for potential application as bone-substituting implants. Using various photocuring techniques, including two-photon 3D printing, both plates and microstructured scaffolds were fabricated. These structures exhibited high thermal stability, elastic properties comparable to those of bone tissue, and no toxic effects on cells. Full article

Intraperitoneal (I.P.) delivery of cell-based therapeutics represents a promising strategy for treating regional peritoneal diseases; however, rapid cellular clearance severely limits therapeutic durability. A critical unmet need is the development of implantable biomaterial platforms that can both mechanically integrate within the dynamic I.P. cavity and sustain viable cell persistence in vivo. Here, we establish a Continuous Liquid Interface Production (CLIP)-based 3D bioprinting strategy to engineer transplantable, cell-laden hydrogel scaffolds optimized for I.P. implantation. Through systematic bioresin design, we identify a GelMA-PEGDA formulation that achieves a balance between high-resolution printability, tissue-matched mechanical characteristics (Young’s modulus 10–15 kPa), and controlled biodegradation (~75% mass loss over 14 days). The resulting constructs support sustained cell viability and proliferation for over 30 days in vitro. Importantly, in an animal study conducted in 6–8 weeks of female nude mice, in vivo I.P. implantation demonstrates a ~10-fold extension in cellular persistence compared to direct cell injection, prolonging the time to 50% signal decay from ~3 days to ~30 days, with detectable cell retention approaching two months in select animals. The platform further accommodates multiple clinically relevant cell types, including human mesenchymal stem cells and neural stem cells, highlighting its translational versatility. Collectively, this work defines key material and architectural parameters required for I.P. implantable cell therapeutics and establishes CLIP-based bioprinting as a scalable strategy for regional delivery of living therapeutics. Full article

Porous hydrogels are critical for tissue engineering and regenerative medicine, as they mimic the native extracellular matrix to support cell infiltration and mass transport. A common strategy for engineering pore structures involves the incorporation and subsequent removal of sacrificial porogen templates (e.g., crystals or microspheres). Although this approach offers excellent control over pore architecture, it often suffers from complex procedures and biosafety concerns arising from incomplete template removal. In this work, we present a simple, biocompatible, and versatile templating approach. By systematically investigating the coacervation parameters, we produced gelatin microspheres (GSs) with tunable diameters from 7 µm to 300 µm via a green, instrument-free, and scalable process. Using GSs of 20–160 µm as porogens, we obtained alginate hydrogels with adjustable viscoelasticity, stiffness, and pore sizes. We then validated two cell-loading strategies for bulk porous alginate hydrogels using immortalized human T (Jurkat) cells: (i) post-seeding into pre-formed pores supported high-density, long-term, and organized cell aggregates with >90% viability; (ii) in situ encapsulation (prior to pore formation) yielded >80% viability and preserved the cluster-forming growth characteristics of Jurkat cells. Moreover, composites of smaller GSs (7–20 µm) with alginate could be syringe-extruded into stable, sub-millimeter porous filaments, demonstrating the potential for 3D printing. Collectively, this work provides a promising platform for three-dimensional culture of immune cells. Full article

Background/Objectives: Intraoperative margin assessments of oral squamous cell carcinoma (SCC) are fundamentally limited by sampling errors and freezing artifacts inherent to standard frozen section analysis. We developed a mobile, multi-scale, wide field-of-view (FOV) swept-source optical coherence tomography/microscopy (SS-OCT/OCM) system operating in the Near-Infrared-II (NIR-II) window (1.68 μm) to provide a rapid, non-destructive, volumetric evaluation of excised oral mucosal tissues. Methods: To correlate optical images with histopathology, we engineered a custom 3D-printed tissue cassette that physically mitigates macroscopic shrinkage during scanning and subsequent tissue fixation. A three-axis motorized assembly extends the effective imaging FOV without compromising resolution, while a custom 3D multi-resolution pyramid stitching algorithm synthesizes wide-FOV mosaics. Results: The customized cassette enabled precise, one-to-one spatial correlation between optical volumes and histopathology sections. Crucially, a 3 × 3 mosaic scan acquired with a 10× objective balanced imaging resolution and acquisition time, providing sufficient structural clarity to visualize basement membrane loss—a hallmark of SCC invasion. Conclusions: This 1.68 μm, fully automatic, multiscale SS-OCT/OCM platform demonstrates the feasibility of serving as a rapid, three-dimensional imaging tool for potential future use as an adjunct to conventional frozen sections. Full article

Bone repair is a complex and dynamic process that demands implanted scaffolds to provide temporal-specific functions: antibacterial activity in the early stage, followed by angiogenic and osteogenic stimulation in later stages. This study introduces a biomimetic scaffold composed of a filled Gel-OSA hydrogel and a 3D-printed PLA framework, enabling sequential multi-drug release for bone regeneration. Zero-dimensional arginine-derived carbon dots were incorporated into the hydrogel to achieve rapid release after implantation, conferring potent antibacterial activity and ROS regulation. Meanwhile, chondroitin sulfate (CS)-loaded mesoporous bioactive glass nanoparticles were immobilized onto the 3D-printed PLA surface via a polydopamine coating, allowing sustained release of CS and Ca/P ions to enhance the scaffold’s long-term osteoinductive capability. The composite scaffold further demonstrated combined effects in promoting cell proliferation and osteogenic differentiation in vitro. Collectively, these findings suggest that this biomimetic scaffold, designed for temporally controlled multi-drug release, represents a promising therapeutic strategy for the reconstruction of bone tissue. Full article

Traumatic injuries often result in nerve tissue damage and functional deficits due to limited regeneration. Silk fibroin, a biopolymer with inherent biocompatibility and tunable properties, is a promising material for 3D-bioprinted neural tissue scaffolds. This review highlights recent advancements in silk-derived composite scaffolds, often incorporating additional materials like collagen or conductive polymers to enhance their performance. This review examines how material composition, scaffold architecture, and fabrication strategy influence biological response and functional recovery. This comprehensive review follows PRISMA guidelines and uses comprehensive searches of PubMed, MEDLINE, Embase, Web of Science, Cochrane Central, and ClinicalTrials.gov for studies published through 2025. Studies were screened for eligibility based on substance type, mechanical properties, production methods, and outcomes. Findings were synthesized qualitatively. Twelve studies were included, comprising rat (50%), canine (8.3%), and in vitro (41.7%) models. Analysis reveals that silk fibroin acts as a highly adaptable mechanical backbone. It can consistently integrate with bioactive additives (collagen, dECM) or conductive polymers (Polypyrrole, MXene) to meet specific therapeutic demands. For spinal cord injuries, composites reached a compressive modulus capable of resisting physiological pressures and preventing scaffold collapse. In soft tissue applications, silk–hydrogel blends provided localized release of exosomes and small molecules during the acute injury phase, reducing neuroinflammatory markers. Additionally, adding conductive materials allowed the scaffolds to bridge electrical gaps and promote Schwann cell proliferation and neuronal differentiation. Furthermore, 3D bioprinting enabled the creation of defined microchannels that replicate native fascicular architecture. In vivo outcomes consistently showed superior axonal regeneration, myelination, and synaptic reconnection compared to controls, correlating with significant improvements in electrophysiological and motor function. This review highlights the clinical potential of silk fibroin-based 3D-printed biomaterials for nerve regeneration, including neural repair and neural tissue engineering. More recent studies place greater emphasis on integrating mechanical, architectural, and biological considerations into scaffold design, resulting in increasingly multifunctional scaffold systems. Despite promising efficacy, the heterogeneity of fabrication methods and the predominance of rodent models highlight the need for standardized protocols and evaluations in relevant models to facilitate clinical translation. Full article

Simulation-based training is increasingly used to support skill acquisition in endoscopic sinus surgery (ESS), although many existing simulators lack objective methods for performance evaluation. This study aimed to assess the face and construct validity of a patient-specific, multi-material 3D-printed sinonasal simulator for ESS using both structured technical scoring and postoperative radiological analysis. Fifteen surgeons with different levels of experience (novices, intermediates, and experts; n = 5 per group) performed a standardized sequence of ESS procedures on identical 3D-printed models, including dacryocystorhinostomy, uncinectomy, maxillary antrostomy, anterior and posterior ethmoidectomy, sphenoidotomy, and frontal sinusotomy (DRAF I). Surgical performance was evaluated on video recordings using a modified Objective Structured Assessment of Technical Skills (OSATS) score. After simulation, each model underwent computed tomography (CT) scanning and a dedicated radiological checklist was applied to assess the adequacy of surgical steps, dimensional parameters of enlarged sinus ostia, and potential procedural complications. Mean OSATS scores differed significantly among expertise levels, with experts achieving higher scores (48.0 ± 1.9) than intermediates (39.4 ± 3.4) and novices (28.4 ± 3.8) (p < 0.01). CT analysis showed a significantly greater extent of ethmoidal cell removal in experts compared with novices (87.5% vs. 57.5%, p = 0.02) and a larger latero-lateral diameter of the frontoethmoidal recess compared with intermediates (p = 0.04). Questionnaire results indicated high perceived educational value, particularly among novices, despite some limitations in haptic realism. While the simulator appears to be a promising tool for ESS training, further studies are required to validate its effectiveness in improving surgical performance. Full article

Background/Objectives: The present study aims to test three different types of PMMA (Fotodent Guide—3D printed (M1), Aidite Temp—milled (M2), Duracryl—self-polymerized (M3) on HFIB-G and on OECM-1. Methods: The two cell types (HFIB-G and OECM-1) were kept in contact with the materials, Fotodent Guide, Aidite Temp, and Duracryl (n = 6), for 24 and 48 h, and subsequently subjected to the following tests: MTT, LDH, NO (according to ISO 10993-5:2009), and immunofluorescent detection of proteins associated with autophagy and apoptosis (mitochondria and caspases 3/7; detection of autophagosomes). Statistical interpretation was made using t-test and ANOVA (* p < 0.05; ** p < 0.01; *** p < 0.001). Results: The MTT assay revealed a reduction in cell viability for all tested materials on gingival fibroblasts compared to control cells, with the most pronounced decrease observed for the 3D-printed material (M1 viability 66.77% for 24 and 52.45% 48 h—p < 0.001), while the self-polymerizing resin (M3 viability 85.92% for 24 h and 85.63% for 48 h) showed the highest level of cellular tolerance (p < 0.001 at 24 h and p < 0.01 at 48 h). Regarding OECM-1 cells, all materials reduced cell viability, particularly M3 after 48 h of incubation (viability 61.79%—p < 0.001). LDH levels generally indicated low membrane damage for all materials. Statistically significant increases in NO levels were recorded for both cell types, suggesting a mild proinflammatory response, especially for M2 OECM-1 48 h—p < 0.05 and M3 (HFIB-G 48 h—p < 0.05, OECM-1 48 h p < 0.05). For both 24 and 48 h, fluorescence analysis demonstrated a significant increase in mitochondrial activity in gingival fibroblasts (p < 0.001), whereas tumor cells exhibited a significantly decreased mitochondrial activity (p < 0.001), particularly for the 3D-printed material M1 (p < 0.001). Caspase-3/7 expression increased in gingival fibroblasts incubated with materials for 24 and 48 h (p < 0.001), while tumor cells showed reduced caspase activity both after 24 and 48 h (p < 0.001). Autophagosome formation decreased initially in fibroblasts at 24 h (p < 0.001) but increased significantly after 48 h (p < 0.001), while tumor cells generally showed enhanced autophagic activity under most experimental conditions (p < 0.001). Conclusions: Our results suggest that all three PMMA-based materials exhibit acceptable biocompatibility profiles, of more than 70%, according to ISO 10993-5:2009, although cellular responses vary depending on the manufacturing technique and the cellular model used. In our study conditions, self-polymerized resin (M3) was the most compatible with gingival fibroblasts, while the 3D-printed and CAD/CAM milled materials (M1 and M2) had a more pronounced impact on cells’ viability and metabolic activity. Full article

Bone grafting remains limited, and the strategies to design even more structurally complex scaffolds—able to reproduce the hierarchical architecture of bone extracellular matrix—are rapidly growing. In this study, we report the fabrication of a hierarchically structured scaffold produced by layering poly(ε-caprolactone)/gelatin (PCL/Gt) or poly(lactic acid)/gelatin (PLA/Gt) electrospun nanofibers via coaxial electrospinning onto 3D-printed poly(lactic acid) (PLA) scaffolds via fused deposition modeling (FDM). After the printing process, PLA disks (10 × 1 mm, 20% infill, ~80% porosity, pore size ~1.57 mm) were coated with core/shell (PCL/Gt, PLA/Gt) fibers to investigate the in vitro interfacial response of osteoblasts in comparison with monocomponent fibrous coatings (PCL, PLA, Gt). SEM and TEM confirmed that core/shell fibers exhibited bead-free morphologies, with a significant reduction in fiber diameter (≈287–316 nm) and higher interfibrillar porosity compared to monocomponent fibers. FTIR and thermogravimetric analyses indicated the presence of hydrogen bonding between the polyester and gelatin, and the absence of residual solvent after deposition. At the same time, water contact angle measurements confirmed an increase in hydrophilic properties from 80–86° to 120° ascribable to the presence of gelatin. Accordingly, in vitro response of human fetal osteoblasts (hFOB 1.19) exhibited an evident improvement in the case of Gt-based fibrous coatings (i.e., PCL/Gt and PLA/Gt) in terms of early adhesion (4–24 h) and metabolic activity from 3 to 21 days, cell spreading into star-shaped morphologies, formation of extracellular matrix, and mineral phase deposition. In more detail, a remarkable increase in alkaline phosphatase activity was observed in Gt-based coaxial coatings from day 7 onward, with the highest values recorded for PLA/Gt. Overall, we demonstrated that the Gt-based coaxial fibrous coating provided a mix of topological and biochemical cues that synergistically promoted key osteoblast activities at the interface, supporting the regeneration of new bone tissue in highly tailored 3D-printed scaffolds, thus suggesting a promising strategy for personalized regenerative medicine. Full article

Anterior cruciate ligament reconstruction relies on interference screw fixation, yet insufficient graft osseointegration remains a critical clinical challenge. This study aimed to develop and characterize a 3D-printed polymeric–hydroxyapatite composite interference screw with an osteoinductive surface to enhance localized osteogenic responses. Screws were designed, modeled, and fabricated using fused deposition modeling 3D printing with a polycaprolactone-poly(lactic-co-glycolic acid)-hydroxyapatite composite. Physico-chemical characterization was performed using scanning electron microscopy. Biocompatibility was assessed through mesenchymal stem cell metabolic activity assays and morphological analysis. Osteogenic gene expression was quantified by RT-qPCR following culture in osteogenic differentiation medium. In vivo osseointegration was evaluated histologically at five and nine weeks following implantation in the proximal tibial epiphysis of a rat model. 3D printing successfully produced screws with consistent geometry and surface characteristics. The composite material supported robust mesenchymal stem cell proliferation without cytotoxicity or morphological abnormalities. Histological examination revealed progressive bone formation with no adverse tissue reactions, including the absence of cyst formation, osteolysis, or excessive fibrosis. RT-qPCR revealed upregulation of osteogenic markers in those enhanced screws. These results indicate that the 3D-printed polymeric–hydroxyapatite composite screws are biocompatible and capable of stimulating localized osteogenic activity, supporting their potential as a biological foundation for future evaluation in anterior cruciate ligament reconstruction applications. Full article