Search Results (418)

Critical-sized bone defects remain a significant clinical challenge, and dipyridamole (DIPY)-coated 3D-tricalcium phosphate (β-TCP) scaffolds have shown promising osteogenic efficacy in preclinical models. However, the literature on the systematic physicochemical characterization of this scaffold system, including optimization of DIPY loading parameters, release kinetics, and surface properties, is lacking. This study addresses these gaps by characterizing DIPY-loaded 3D-printed β-TCP scaffolds across solid and porous architectures, three coating concentrations (10, 100, and 1000 µM), and three coating volumes (250, 500, and 1000 µL). Under static PBS conditions, drug release over 21 days was quantifiable only at 1000 µM, and release-kinetics modeling (zero-order, Higuchi, and Korsmeyer–Peppas) was therefore restricted to this highest concentration. At 1000 µM, both scaffold types showed biphasic release profiles, with standard empirical models reasonably approximating the overall kinetics, while not fully capturing the biphasic behavior over the entire duration. Porous scaffolds showed significant volume-dependent release (p = 0.002, η² = 0.88), attributable to drug penetration into the interconnected macropore network, whereas solid scaffolds displayed volume-independent release confined to external surfaces. Scanning electron microscopy revealed concentration-dependent needle-shaped DIPY crystal deposition while contact angle measurements indicated no significant changes in surface hydrophilicity. MTT assay demonstrated biocompatibility at all concentrations, with viability influenced by coating volume rather than drug concentration. These findings establish a foundational physicochemical framework for DIPY-loaded β-TCP scaffolds, providing the baseline data necessary to guide subsequent biological evaluation and translational efforts toward critical-sized craniofacial and orthopedic bone defect repair. Full article

As the population ages, the demand for customizable, resorbable bone implants in tissue engineering has intensified, outstripping the limitations of traditional autografts and allografts. While silicate-based bioactive glasses dominate bioactive glass research, borate-based bioactive glasses (BBGs) present distinct biomimetic advantages due to their accelerated degradation kinetics and superior ion-release profiles. However, producing highly pure, homogeneous BBG powders tailored for additive manufacturing remains a severe bottleneck. This study reports the development of a highly efficient synthesis protocol and subsequent Digital Light Processing (DLP) 3D printing of BBG scaffolds. An aqueous-based precursor mixture was processed via spray drying and a customized multi-stage thermal pretreatment sequence up to 800 °C to mitigate material loss, minimize oxide evaporation, and completely eliminate carbonates. Subsequent “flash melting” at 1150 °C for 20 min yielded an amorphous, high-purity borate–phosphate glass network (68.1B₂O₃-3.8Na₂O-18.9CaO-4.9MgO-4.3P₂O₅, in wt%). Differential scanning calorimetry (DSC) revealed a glass transition temperature ($T_g$) of 625 °C, while in situ X-ray diffraction localized the onset of crystal nucleation between 706 °C and 723 °C. Following fine planetary milling to achieve a highly dense particle packing distribution (D_v50 = 5.4 µm, D_n50 = 0.6 µm), the optimized BBG powder was successfully loaded into an acrylate-based photosensitive slurry (51.2 wt% solid loading) to manufacture complex 3D biomimetic gyroid scaffolds via DLP. While the structural feasibility of printing high-resolution gyroid porous architectures is validated, post-printing evaluation highlighted a narrow thermal processing window; sintering at 660 °C optimized particle coalescence while minimizing microstructural de-densification caused by closed porosity expansion (which reaches 48.4% at 675 °C). This scalable synthesis-to-printing workflow offers a crucial steppingstone toward next-generation fully resorbable bone tissue scaffolds. Full article

Pullulan, a natural microbial polysaccharide composed of repeating maltotriose units, is widely explored as a candidate for advanced cell culture configurations, tissue engineering (TE), and regenerative medicine (RM). Due to its excellent biocompatibility, lack of immunogenicity, and structural flexibility, it serves as a versatile base material. Pristine pullulan exhibits high water solubility and lacks intrinsic signals for cell attachment and proliferation. However, the presence of nine reactive hydroxyl groups per repeating maltotriose unit enables extensive chemical functionalization to address these limitations. This review provides a comprehensive analysis of multi-functional design strategies used to tailor pullulan into distinct structural forms, such as hydrogels, porous scaffolds, electrospun fibrous membranes, thin films, 3D-printed scaffolds, and self-assembling nanosystems. Polymer blending, chemical modification, and crosslinking strategies are discussed in relation to scaffold microstructure, pore size, degradation rate, and mechanical properties. In addition, these structural and physicochemical properties are correlated with biological performance, including cell migration, proliferation, and differentiation. Pullulan-based materials are particularly suited for applications requiring extensive chemical tunability, such as injectable hydrogels, bioinks, and multifunctional delivery systems. However, their intrinsic bioinertness and limited mechanical strength generally require combination with complementary components to achieve effective cell adhesion and structural stability. Finally, current processing limitations and future strategies are discussed for translating pullulan-based systems into clinical applications. Full article

Three-dimensional (3D) graphene foams are attractive as lightweight conductive scaffolds with large surface area and broadband light absorption but achieving reproducible porosity and preserving the architecture after metal-template removal remain challenging. Here we report a stepwise route to freestanding 3D multilayer graphene foams based on (i) hydrogen-bubble-assisted electrodeposition of porous Ni on Cu foils, (ii) time-controlled pre-annealing at 1000 °C to drive Cu diffusion and form porous Ni-Cu alloy templates, (iii) in situ graphene CVD at 1000 °C under fixed growth conditions, and (iv) wet etching to remove the metal scaffold without a polymer support. The influence of pre-annealing (0, 1, 3, and 7 h) on template evolution, graphene growth, and foam stability was systematically investigated via SEM, EDS, XRD and Raman studies. Before etching, Raman spectroscopy indicates low-defect graphenic coatings with locally heterogeneous few-layer-like to multilayer-like signatures. Only samples pre-annealed for at least 3 h preserved the porous 3D architecture after metal removal, indicating the formation of self-supporting graphenic networks with improved post-etch morphological stability. Raman and XRD analyses further revealed a progressive reduction in structural degradation, residual strain, and stacking disorder with increasing pre-annealing time. Among the investigated samples, the foams obtained after 3 and 7 h of template pre-annealing combined preserved 3D morphology with low sheet resistance (10–20 Ω/□), negligible optical transmittance (<5%), and strong broadband visible-light absorption (75–90%). 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

The use of biogenic hydroxyapatite as a sustainable and bioactive alternative to synthetic ceramics has attracted increasing attention for 3D-printed scaffolds in bone tissue engineering. In this work, calcium alginate-based scaffolds reinforced with commercial (cHA) and biogenic hydroxyapatite (bHA) obtained from croaker fish bones (Micropogonias furnieri) were fabricated by 3D printing using hydroxyapatite contents ranging from 10% to 20%. Both hydroxyapatites exhibited hexagonal structures, and all formulations showed rheological behavior suitable for extrusion-based printing. Structural analyses revealed increased diffraction peak intensity with higher hydroxyapatite content, while FTIR spectra showed no significant structural changes. Hydroxyapatite addition increased the compressive modulus, although higher loadings reduced maximum resistance and produced denser, less porous structures. After 14 days in simulated body fluid, scaffolds containing 10% bHA favored apatite deposition, evidenced by increased phosphorus levels. In vitro assays using MC3T3-E1 pre-osteoblasts demonstrated biocompatibility, with metabolic viability above 70% and no toxicity. The 10% bHA formulation also enhanced cell proliferation, adhesion, and migration without increasing reactive oxygen or nitrogen species. Alizarin Red staining indicated osteogenic potential, while micronucleus assays with CHO-K1 cells confirmed the absence of genotoxicity. These findings highlight the potential of biogenic hydroxyapatite scaffolds for bone tissue engineering. Full article

Osteochondral defects, involving both articular cartilage and subchondral bone, can lead to joint degeneration and osteoarthritis. Recent advances in 3D-printed biphasic scaffolds offer promising opportunities to recreate physiological microenvironments for tissue regeneration. In tissue engineering, these scaffolds can be mechanically stimulated to promote targeted cartilage and bone formation. While computational models have been widely used to study mechanically induced cellular responses in monophasic scaffolds, time-dependent modelling of biphasic osteochondral systems remains relatively scarce. In this study, a fluid–structure interaction (FSI) framework coupled with a mechanoregulatory algorithm was developed to predict mechanically induced early-stage mesenchymal stem cell (MSC) differentiation in biphasic open-porous osteochondral scaffolds comprising chondral and bone layers designed for direct ink writing (DIW). In a second model, an interfacial barrier layer representing the native osteochondral interface was integrated. Dynamic compressive loading (1 Hz, $2.5\%$ strain) was applied. The simulations predicted region-specific differentiation patterns in both the chondral and subchondral bone regions. In the scaffold without a barrier layer, approximately $68.9\%$ of MSCs in the chondral layer and $93.4\%$ of MSCs in the bone layer underwent chondrogenic and osteogenic differentiation, respectively. Incorporation of the barrier layer caused only minor changes, reducing predicted cartilage and bone differentiation by approximately $1.5\%$ and $3.9\%$, respectively. Overall, this study highlights the capability of computational modelling to predict mechanobiological responses in complex osteochondral systems and support scaffold design and effective mechanical stimulation protocols. Full article

This study reports the fabrication of curcuminoid-loaded nanofibrillated cellulose (NFC)–alginate scaffolds via extrusion-based 3D printing, integrating supercritical CO₂ extraction with biofabrication. NFC–alginate inks were pre-crosslinked with CaCl₂ (1 to 10 mM) to tune structure and properties. Rheological analysis confirmed shear-thinning behavior suitable for extrusion printing. Mechanical testing revealed a non-linear dependence on crosslinking: optimal performance was achieved by Ink 2 (1 mM CaCl₂ with curcuminoid extract), with tensile strength increasing from ~0.60 to ~0.80 MPa and Young’s modulus from ~1.5 to ~3.0 MPa relative (Ink 1, 10 mM CaCl₂, without extract), reflecting the combined effect of extract incorporation and ionic pre-crosslinking rather than crosslinker concentration alone; higher crosslinking reduced stiffness (~1.15 MPa). SEM revealed porous architectures (Ink 1: 542 ± 63 μm; Ink 4: 398 ± 71 μm) with increasing structural heterogeneity upon curcuminoid incorporation. In vitro release exhibited biphasic, diffusion-dominated behavior, reaching ~50 to 60% in ethanol-containing media; PBS inclusion as a physiological reference confirmed minimal release (<5%), consistent with the known hydrophobicity and pH-dependent instability of curcuminoids and defining the physicochemical delivery boundaries of the system. The highest release (~372 ng/mL) was achieved at intermediate loading (10×). Kinetic modeling confirmed Higuchi-type diffusion as the dominant mechanism (R² ≈ 0.90 to 0.99). These results establish a clear structure–property–release relationship and position the scaffolds as a tunable, diffusion-controlled delivery platform for hydrophobic bioactives in topical or formulation-assisted applications employing co-solvents or solubilizing excipients. Full article

Porous silicate scaffolds represent a promising class of grafting materials for hard tissue engineering due to their superior bioactivity, adjustable degradation rates, and ability to stimulate both osteogenesis and angiogenesis. In this work, scaffolds based on an akermanite-targeted (Ca₂MgSi₂O₇) starting composition, including copper-doped variants, were synthesized using sol–gel and combustion routes, followed by 3D printing to achieve porous architectures with controlled pore size and interconnectivity. The powders were characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and thermal analysis to evaluate their morphology, composition, and crystalline phases. The scaffolds were further assessed in terms of bioactivity by immersion in simulated body fluid (SBF), antibacterial activity, and in vitro cellular response. The results confirmed that copper doping enhanced antibacterial properties, while maintaining favorable biological behavior. Comparative analysis revealed differences between the two synthesis methods, with sol–gel providing more homogeneous structures and combustion leading to highly porous morphologies. These findings highlight copper-doped silicate scaffolds as promising candidates for bone tissue regeneration, combining architectural integrity with biological functionality. Full article

This study provides a comprehensive characterization of carbon dust adhesion on the anode surface induced by the anode effect (AE) in the Hall–Héroult process. The primary objective was to verify the hypothesis of electrophoretic carbon particle transport and its subsequent stabilization on the electrode substrate. Unlike previous studies conducted in horizontal configurations where gravitational sedimentation could interfere with observations, this research employs a unique vertical electrode setup to provide direct physical evidence of purely electrophoretic transport. Authentic industrial carbon dust was used as a tracer material, its presence on the high-purity graphite surface being definitively confirmed through the detection of trace markers (Mg, Ca) via SEM-EDS. The multiscale structural analysis revealed that spike initiation occurs through a dynamic arc-induced nucleation mechanism. Morphological observations suggest that micro-arc discharges during the AE provide the extreme localized energy for direct carbon-to-carbon “welding,” creating a conductive, porous scaffold on the vertical anode wall. XRD analysis identified crystalline cryolite (Na₃AlF₆) and chiolite (Na₅Al₃F₁₄) within this structure. It was demonstrated that these fluoride phases represent the solidified product of molten, acidic electrolyte infiltration into the carbonaceous matrix via capillary action, rather than acting as binders that crystallize during the process. Raman spectroscopy confirmed the disordered, amorphous nature of the captured dust (high D-band intensity), distinguishing it from the highly ordered graphite substrate. Confocal microscopy visualized the topographical evolution from isolated clusters to interconnected three-dimensional “islands” as a function of AE duration. The results demonstrate that the anode effect serves as a critical flashpoint where synergistic electrophoretic forces and localized thermal anomalies initiate the growth of stable, conductive carbon–matrix composite spikes, providing new insights for mitigating current efficiency losses in industrial smelters. Full article

Traumatic Brain Injuries (TBIs) frequently require cranioplasty procedures to restore skull integrity and protect underlying brain. Conventional cranial implants are often limited by inadequate osteointegration, risk of inflammation, infection, or the need for secondary surgical interventions. In this study, a multifunctional strategy for cranial reconstruction is proposed, combining additive manufacturing, bioactive surface functionalization, and local drug delivery. Porous polylactic acid (PLA) scaffolds were fabricated by Fused Deposition Modelling (FDM) to obtain lightweight structures with controlled porosity. The scaffolds were subsequently functionalized with hydroxyapatite coatings, deposited through sol–gel, to provide osteointegrative properties. To locally modulate post-implant inflammatory responses, a drug delivery system based on polycaprolactone (PCL) microparticles loaded with dexamethasone was developed and entrapped within hydroxyapatite-coated PLA structures. The produced systems were extensively characterized in terms of morphology, mechanical and thermal behavior, structural properties, biological response, and drug release behavior. Results demonstrated that the 3D-printed scaffolds exhibited homogeneous hydroxyapatite coatings, whose continuity and retention were enhanced by NaOH surface pre-treatment. Biological assays demonstrated that HAp coating significantly improved cell viability and osteogenic differentiation, confirming the osteoconductive potential of the scaffolds for craniofacial bone regeneration applications. Dexamethasone-loaded PCL microparticles were successfully integrated into the coated scaffolds, exhibiting controlled drug release, absence of cytotoxicity, and homogeneous distribution within the porous architecture, thereby demonstrating the feasibility of a multifunctional platform combining bone-regenerative and therapeutic delivery functionalities. Overall, the proposed multifunctional scaffolds represent a promising, low-cost and customizable approach for advanced cranioplasty applications, integrating structural support, osteointegration and local anti-inflammatory therapy within a single system. Full article

Critical-sized bone defects lack spontaneous healing capacity. While mesenchymal stem cell-derived exosomes (sEVs) are promising osteoinductive agents, their rapid in vivo clearance limits their free-form efficacy. Here, we fabricated a nano-hydroxyapatite/chitosan (nHA/CTS) composite scaffold as a protective, sustained-delivery platform for human umbilical cord blood-derived mesenchymal stem cell exosomes (HUCB-MSCs-exos) to accelerate bone repair. The 3D porous CTS/10% nHA scaffold exhibited excellent cytocompatibility and a degradation rate commensurate with new bone ingrowth. Critically, it enabled a biphasic exosome release profile—an initial burst followed by a 14-day sustained release (89.73% cumulative release). In vitro, HUCB-MSCs-exos significantly promoted the proliferation, migration, and osteogenic differentiation of bone marrow-derived MSCs, as demonstrated by enhanced alkaline phosphatase activity and matrix mineralization. In a rabbit condylar defect model (5 mm diameter), the CTS/10% nHA-exo scaffold achieved a 57.44 ± 8.42% healing rate at two months, nearly two-fold greater than the scaffold-only group (29.33 ± 6.94%). Histological and immunohistochemical analyses at two months confirmed the formation of mature, well-vascularized trabecular bone, accompanied by robust expression of late-stage osteogenic markers (OCN and OPN). These findings demonstrate that the CTS/10% nHA scaffold synergistically integrates osteoconductive structural guidance with exosome-mediated osteoinductive paracrine signaling, providing a compelling and translatable strategy for critical-sized bone-defect management. Full article

This study presents a transformative “one-pot” biorefinery approach for the simultaneous production of hyaluronic acid (HA) and polyhydroxybutyrate (PHB) using an engineered, non-pathogenic Halomonas bluephagenesis TD01 chassis. By leveraging the principles of Next-Generation Industrial Biotechnology (NGIB), a one-step fermentation process was developed in nutrient-rich 40-LBG-Y medium, achieving a balanced metabolic flux that yielded 1.99 g/L and high-molecular-weight (HMw) HA (9.6 × 10⁶ Da) as the highest HA-Mw reported by heterogeneous bacteria, alongside intracellular PHB (0.68 to 1.6 g/L). A bioactive HA-PHB nanoparticle scaffold was fabricated, exhibiting a highly porous, interconnected 3D sponge-like architecture with a significant particle size shift from 12 nm to 450 nm, confirming successful polymer complexation. Antimicrobial evaluations revealed that the scaffold exhibited preliminary antimicrobial potential against representative Gram-positive and Gram-negative strains against Staphylococcus aureus, Klebsiella variicola, and Candida albicans. Notably, while Pseudomonas aeruginosa metabolically exploited purified HA, the integrated scaffold reversed this effect, providing preliminary antimicrobial potential by sterically hindering bacterial hyaluronidases. Furthermore, Halomonas-derived HA consistently outperformed Moringa oil and complex emulsions in preliminary tests against a wide range of pathogenic microbes. These results demonstrate that this dual-product platform provides a sustainable, cost-effective source of high-performance functional materials for advanced antimicrobial coatings and clinical wound management. 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

Polyhydroxyalkanoates (PHAs) are bio-based, biodegradable polyesters increasingly explored as sustainable biomaterials for regenerative medicine. This review summarizes recent advances in PHA-based bone substitute materials, highlighting their properties, fabrication methods, and biological performance. PHAs combine biocompatibility, tunable mechanical behavior, and degradation into non-toxic metabolites, while copolymerization and monomer selection modulate the stiffness, crystallinity, and resorption rate. Processing techniques such as solvent casting, electrospinning, and additive manufacturing allow the production of porous architectures that mimic bone extracellular matrix. Electrospinning is particularly suitable for nanoscale fibrous matrices, whereas 3D printing enables patient-specific scaffolds with controlled geometry and interconnected porosity. Scaffold performance can be further improved through the incorporation of osteoconductive fillers, including hydroxyapatite, β-tricalcium phosphate, bioactive glasses, graphene oxide, and carbon nanotubes, as well as through drug-delivery and pro-angiogenic functionalization. In vitro and in vivo studies consistently report favorable cytocompatibility, enhanced osteogenic differentiation, vascularization, and effective repair of bone defects in animal models. However, clinical translation remains limited by production costs, variability in polymer quality, thermal processing constraints, and regulatory challenges. Future progress will rely on more efficient biosynthesis, medical-grade purification, multifunctional scaffold design, and stronger collaboration between academia, industry, and clinicians to unlock the full potential of PHAs in regenerative bone therapies. Full article