Search Results (449)

Neural tissue injuries, including spinal cord damage and neurodegenerative diseases, pose a major clinical challenge due to the central nervous system’s limited regenerative capacity. Current treatments focus on stabilization and symptom management rather than functional restoration. Tissue engineering offers new therapeutic perspectives, particularly through the combination of electrospun nanofibrous scaffolds and mesenchymal stem cells (MSCs). Electrospun fibers mimic the neural extracellular matrix, providing topographical and mechanical cues that enhance MSC adhesion, viability, and neural differentiation. MSCs are multipotent stem cells with robust paracrine and immunomodulatory activity, capable of supporting regeneration and, under proper stimuli, acquiring neural-like phenotypes. This systematic review, following the PRISMA 2020 method, analyzes 77 selected articles from the last ten years to assess the potential of electrospun biopolymer scaffolds for MSC-mediated neural repair. We critically examine the scaffold’s composition (synthetic and natural polymers), fiber architecture (alignment and diameter), structural and mechanical properties (porosity and stiffness), and biofunctionalization strategies. The influence of MSC tissue sources (bone marrow, adipose, and dental pulp) on neural differentiation outcomes is also discussed. The results of a literature search show both in vitro and in vivo enhanced neural marker expression, neurite extension, and functional recovery when MSCs are seeded onto optimized electrospun scaffolds. Therefore, integrating stem cell therapy with advanced biomaterials offers a promising route to bridge the gap between neural injury and functional regeneration. Full article

Background/Objectives: Finite element analysis (FEA) can predict biomechanical performance of dental implants in compromised bone. In the posterior maxilla, low bone density, thin cortex, and variable regenerated bone stiffness may lead to pathological peri-implant strains. This study examined the effects of implant diameter, cortical thickness, cancellous bone type, and regenerated bone elasticity on strain distribution in short plateau (Bicon SHORT^®) implants. Methods: Three-dimensional FEA models of type III and IV maxillae with cortical layers of 1.0, 0.75, and 0.5 mm were developed. Implants of 4.5, 5.0, and 6.0 mm diameter were tested, with regenerated bone elasticity set to 25–100% of cortical values. An oblique load of 120.9 N at 75° was applied under full osseointegration, and first principal strains were compared with Frost’s 3000 με threshold. Results: Cortical strains remained at physiological levels, but cancellous bone in type IV often exceeded 3000 με, especially with smaller diameters and low regenerated stiffness. Enlarging implant diameter to 6.0 mm lowered cancellous maximal first principal strain by up to 56% in type III and 36% in type IV bone. Reduced regenerated bone elasticity markedly increased risk, particularly with cortical thickness < 0.75 mm. Conclusions: Biomechanical risk depends on implant diameter and regenerated bone quality. Wide short implants (6.0 mm) most effectively limited pathological strain under low cortical support and poor regenerated stiffness. Patient-specific FEA may guide implant choice and improve outcomes in atrophic maxilla rehabilitation. Full article

The reconstruction of segmental bone defects requires patient-specific scaffolds that combine mechanical safety, biological functionality, and rapid manufacturing. We converted CT-derived mandibular geometry into a functionally graded Ti-6Al-4V lattice and optimised porosity, screw layout, and strut thickness through a cyber-physical loop that joins high-fidelity FEM, millisecond ANN, and a BN for uncertainty quantification. Fifteen candidate scaffolds were fabricated by direct metal laser sintering and hot isostatic pressing and were mechanically tested. FEM predicted stress and stiffness with 98% accuracy; the ANN reproduced these outputs with 94% fidelity while evaluating 10,000 designs in real time, and the BN limited failure probability to <3% under worst-case loads. The selected 55–65% porosity design reduced titanium use by 15%, shortened development time by 25% and raised multi-objective optimisation efficiency by 20% relative to a solid-plate baseline, while resisting a 600 N bite with a peak von Mises stress of 225 MPa and micromotion < 150 µm. Integrating physics-based simulation, AI speed, and probabilistic rigour yields a validated, additively manufactured scaffold that meets surgical timelines and biomechanical requirements, offering a transferable blueprint for functional scaffolds in bone and joint surgery. Full article

Background/Objectives: Patients suffering from fractures are often treated with clopidogrel during the phase of bone healing due to multiple comorbidities. Studies indicate that clopidogrel suppresses osteoblast proliferation and the formation of trabecular bone. However, it is unknown whether clopidogrel also affects fracture healing under ischemic conditions, as they may occur in multimorbid patients. Methods: To test this in the present study, a murine ischemia model was performed in CD-1 mice by ligating the right deep femoral artery to induce mild ischemia of the right lower limb. A closed fracture of the femur was then stabilized by inserting an intramedullary lag screw. The animals received either 3 mg/kg body weight clopidogrel daily per os or vehicle (control). Bone healing was assessed by biomechanical, radiological, histomorphometrical and Western blot analyses 2 and 5 weeks postoperatively. Results: The fractured femurs in the clopidogrel group exhibited no increase in biomechanical stiffness throughout the observation period in contrast to controls. While the radiological analysis showed no differences between both groups, histomorphometric analyses demonstrated a significantly reduced bridging score, less bone and more connective tissue within the callus of clopidogrel-treated animals. Western blot analyses revealed a significantly reduced expression of the osteogenic marker bone morphogenetic protein (BMP)-4 and an increased expression of the blood vessel marker CD31. Conclusions: These results show that clopidogrel may impair fracture healing under challenging ischemic conditions, which is associated with a shift in angiogenic and osteogenic expression markers in the callus tissue. Therefore, clopidogrel treatment may not be recommended in fracture patients with tissue ischemia. Full article

The demand for patient-specific medicine is steadily increasing, particularly with the need for innovative materials capable not only of supporting tissue regeneration but also accelerating it. The aim of this study was to develop a new printable composite material exhibiting ductile behavior, in contrast to brittle failure, in order to support cell growth even under structural compromise. PBS was selected as a blending component with PLA due to its enhanced biocompatibility for bone tissue regeneration. Both neat PLA and the PLA/PBS blend were subsequently combined with BaTiO₃, processed into filaments, 3D printed, and subjected to mechanical testing. PLA-based composites demonstrated higher stiffness under compression, with up to a 6.5% increase in Young’s modulus compared to the blended samples. However, the incorporation of PBS resulted in a more ductile response, as evidenced by three-point bending tests, even at BaTiO₃ concentrations of 10 wt%. This improved ductility is expected to provide safer conditions for cell growth and enable elastic recovery following mechanical loading. Full article

Objective: This study investigated associations between physical activity (PA) during late adolescence and emerging adulthood and bone strength in emerging adulthood by utilizing advanced finite element analysis of computed tomography (CT/FEA) technology beyond the traditional dual-energy X-ray absorptiometry (DXA) method. Methods: This study included 266 participants (152 females) from the Iowa Bone Development Study. PA volume (average acceleration) and intensity (intensity gradient) metrics were calculated from ActiGraph accelerometer data collected at ages 17, 19, 21, and 23 years. Compressive modulus and compressive stiffness of the tibia were estimated at age 23 via CT/FEA of the tibia. Sex-specific linear regression models were used to evaluate associations between PA metrics and bone outcomes, adjusting for age, height, weight, musculoskeletal fitness, and calcium intake. Results: Intensity gradient averaged over 17–23 years of age was positively associated with compressive stiffness at age 23 years in both females and males (p < 0.01). Intensity gradient was positively associated with compressive modulus in females (p < 0.01), but not in males. No significant associations were found between average acceleration and either compressive stiffness or modulus in either sex (p > 0.05). Conclusions: Using a state-of-the-art CT/FEA method, this study suggests that high-intensity PA during late adolescence and emerging adulthood improves bone strength. Full article

The integration of nanomaterials within hydrogel scaffolds offers significant promise in bone tissue engineering by improving mechanical performance and modulating cellular responses through mechanotransductive and biochemical signaling. Previous studies have demonstrated that nanodiamonds (NDs) incorporated in electrospun microfibrillar meshes enhance cellular adhesion, spreading, and cytoskeletal organization through localized mechanical reinforcement. However, the effects of ND loading into soft, bioinert three-dimensional hydrogel matrices remain underexplored. Here, we developed nanostructured 3D printing inks composed of gellan gum (GG) supplemented with a low content of ND nanoadditive (0–3% w/v). ND integration improved the shear-thinning properties of the formulation, enabling consistent filament formation and reliable extrusion-based 3D printing. Structural and mechanical assessments confirmed enhanced scaffold morphology, reduced deformation, and improved morphostructural integrity under compression and increased local stiffness at 2% ND loading (GG_ND2%). Biological assessments revealed that increasing ND content enhanced murine preosteoblast viability, proliferation, and attachment, particularly in GG_ND2%. Furthermore, bioactivation of the GG_ND2% formulation with icariin (ICA), a bioflavonoid known for its osteogenic and angiogenic activity, amplified the beneficial cellular responses of MG-63 cells to ND loading, promoting enhanced surface mineralization and improved cell–matrix interactions. Collectively, these findings highlight the potential of ND-reinforced GG scaffolds bioactivated with ICA, integrating structural reinforcement and biological functionalities that may support osteogenic responses. Full article

Sim, a potent HMG-CoA reductase inhibitor, exhibits notable anabolic effects on bone and can upregulate osteogenic genes such as BMP-2, thereby promoting bone formation. An ideal drug delivery system for Sim involves its controlled and sustained release at the defect site to minimize adverse side effects. In this study, Sim was first modified via HP-γ-CD to form a hydrophilic Sim/HP-γ-CD inclusion complex, thereby improving drug solubility and dispersion in aqueous systems. A gelatin–sodium alginate (Gel/SA) hydrogel was then employed as the drug delivery matrix to construct a Gel-SA-Sim/HP-γ-CD hydrogel sustained release system. This hydrogel system exhibited a high water content (82%), along with enhanced mechanical properties, including a compressive strength of 0.284 MPa and a compressive modulus of 0.277 MPa, suggesting strong load-bearing capacity and favorable stiffness. Importantly, Sim was released in a controlled and sustained manner over 7 days, without exhibiting burst release behavior. In vitro osteogenic differentiation assays demonstrated that optimal concentrations of Sim effectively enhanced cellular bioactivity and osteoinductive performance, offering a promising approach to enhance the bioactivity, osteogenesis, and osseointegration of orthopedic implants. Full article

Additive manufacturing technology, specifically material extrusion, offers great potential for scaffold manufacturing in tissue engineering. This study presents a novel methodology for the design and optimization of 3D printed polymeric scaffolds to enhance cell viability, thereby promoting improved cell proliferation for tissue engineering applications. Different infill patterns, including gyroid, parallel sinusoidal, and symmetric sinusoidal, were evaluated to determine their impact on cell proliferation and tissue regeneration. To overcome the limitations of existing slicer software, a novel open-source software called FullControl GCode Designer was utilized, enabling the creation of customized infill patterns without restrictions. VOLCO software was employed to generate voxelized 3D models of the scaffolds, simulating the material extrusion process. Finite element analysis was conducted using Abaqus software to evaluate the mechanical properties of the different designs. Additionally, new scripts were developed to evaluate the interconnectivity and pore size of the voxelized models. A factorial design of experiments and a genetic algorithm (combined with Kriging metamodels) were applied to identify the optimal configuration based on optimization criteria (keeping the mechanical stiffness and pore size within the recommended values for trabecular bone and maximizing the surface and interconnectivity). Biological testing was conducted on polylactic acid scaffolds to preliminarily validate the effectiveness of the modeling and optimization methodologies in this regard. The results demonstrated the agreement between the optimization methodology and the biological test since the optimum in both cases was a symmetric sinusoidal pattern design with a configuration resulting in a structure with 53.08% porosity and an equivalent pore size of 584 µm. Therefore, this outcome validates the proposed methodologies, emphasizing the role of pore surface area and interconnectivity in supporting cell proliferation. Overall, this research contributes to the advancement of AM technology in tissue engineering and paves the way for further optimization studies in scaffold design. Full article

This in vivo animal study aimed to evaluate the effects of two different implant placement micromotor systems on implant stability and removal torque. In a within-animal crossover design, twenty titanium implants (AnyOne fixture; internal type; diameter, 3.5 mm; length, 7.0 mm; Megagen, Daegu, Republic of Korea) were placed in the tibiae of five rabbits using a conventional micromotor system (NSK group: SurgicPro+; NSK, Kanuma, Japan) and a diode laser-integrated micromotor system (SAESHIN group: BLP 10; Saeshin, Daegu, Republic of Korea). Resonance frequency analysis provided the implant stability quotient (ISQ) immediately after placement and at four weeks. Micro-computed tomography quantified the bone–implant interface gap (BIG). Removal torque was measured at sacrifice. Linear mixed-effects models with a random intercept for rabbit generated adjusted means with 95% confidence intervals (CIs) (α = 0.05). Equivalence for the four-week ISQ used two one-sided tests with a margin of ±5 ISQ. The SAESHIN group achieved a higher immediate ISQ than the NSK group (difference =+6.9 ISQ; 95% CI +1.3–+12.5; p = 0.018). At four weeks, the ISQ did not differ (difference = −1.2 ISQ; 95% CI −4.3–+1.9; p = 0.42), and equivalence was supported (TOST p_lower = 0.024; p_upper = 0.019). Removal torque was comparable (difference = +4.3 N·cm; 95% CI −5.2–+13.8; p = 0.36). BIG metrics showed no between-system differences across regions. ICC indicated clustering for ISQ and torque (0.36 and 0.31). The diode laser-integrated micromotor system yielded a higher immediate ISQ under a standardized 35 N·cm seating torque, whereas the ISQ, removal torque, and BIG at four weeks were comparable to those of the conventional system. The immediate ISQ should be interpreted as stiffness under fixed torque rather than superior device-dependent interlocking. These findings support the clinical interchangeability of the two systems for early osseointegration endpoints in preclinical settings. Full article

Poly(L-lactic acid) (PLLA) and iron (Fe) are popular bioresorbable material candidates for biomedical implants. However, PLLA coronary stents are relatively too thick compared to metallic stents when providing the same mechanical strength, while iron degrades too slowly. Recent studies show that PLLA coatings can enhance iron’s corrosion rate, and iron has strong mechanical strength, making PLLA–Fe composites ideal for bioresorbable implants. Although PLLA coatings on iron samples have been studied, research on embedding iron wires in relatively thick PLLA matrices is limited. Moreover, no studies have yet explored 3D-printed metal wire-reinforced PLLA monofilaments for biomedical applications. To address these research gaps and investigate the in vitro degradation profile of PLLA/Fe wire monofilaments for bioresorbable stents, this study first developed a novel polymer filament–metal wire coextrusion 3D printer for printing PLLA/Fe wire monofilaments. In vitro degradation tests were then conducted on both PLLA/Fe and neat PLLA monofilaments at 50 °C. Thereafter, characterizations, including mass loss, pH, surface appearance and morphology, tensile tests, gel permeation chromatography (GPC), and differential scanning calorimetry (DSC), were performed. Results indicated that the overall degradation rate of PLLA/Fe monofilaments was higher than that of PLLA counterparts, while the degradation rate of PLLA matrix was not affected by the embedded iron wire according to molecular weight analysis. Notably, the Young’s modulus and stiffness of PLLA monofilaments were significantly improved by the iron wires during the early stages of degradation, but the reinforcement in tensile strength was negative after immersion due to the poor embedding quality of the iron wires in the PLLA monofilaments. With future improvement of the embedding quality of iron wire, the 3D-printed PLLA/Fe wire composites can have great potential in the development of biomedical devices using the novel 3D printing method, including most types of stents and bone scaffolds. Full article

There is evidence that bone health is closely linked to a functioning circadian rhythm. Most of the evidence comes from mice, which may exhibit some species-specific differences from humans due to their nocturnal lifestyle. To address the current lack of human model systems, the present study aimed to develop an in vitro model system that can represent diurnal changes in bone metabolism. The model is based on co-cultured SCP-1 and THP-1 cells that serve as osteoblast and osteoclast precursors, respectively. Diurnal effects were induced by replacing the FCS in the differentiation medium with human serum pools (HSPs) obtained in the morning, noon, or evening. The model system was tested for cell viability, gene expression, and osteoblast and osteoclast function. The replacement of the FCS with the HSPs increased viability and induced expression changes in circadian clock genes in the model system. Resulting alterations in osteoblast and osteoclast function led to a gradual increase in mineral density and stiffness when 3D co-cultures were differentiated in the presence of the HSPs collected in the morning, noon, or evening, respectively. Here, we present for the first time an in vitro model that can present diurnal changes in bone metabolism in the form of a snapshot. With the simple use of HSPs, this model can be used as a platform technique to investigate bone function in various situations, taking into account the time of day. Full article

Red blood cell (RBC) production from bone marrow hematopoietic stem cells (BMHSCs) in vitro overlooks the mechanical signals of the bone marrow niche and overly relies on growth factors. Considering that the fate of hematopoietic stem cells (HSCs) is determined by the natural bone marrow microenvironment, differences in mechanical microenvironments provide a reference for the regulation of HSC differentiation. This study seek to reveal the role of mechanobiology cues in erythropoiesis and provide a new perspective for the design of in vitro erythropoiesis platforms. The hydrogel platforms we designed simulate the stiffness gradient of the bone marrow niche to culture HSCs and induce their differentiation into the erythroid system. Cells on the low-stiffness scaffold have higher potential for erythrocyte differentiation and faster differentiation efficiency and promote erythrocyte differentiation after erythropoietin (EPO) restriction. In vivo transplantation experiments demonstrated that these cells have the ability for continuous proliferation and differentiation into mature erythrocytes. By combining mechanical cues with in vitro erythrocyte production, this method is expected to provide insights for in vitro hematopoietic design and offer a scalable cell manufacturing platform for transfusion medicine. Full article

Background: The relationship between spleen and bone marrow stiffness, and other features of abnormal myeloproliferation has long been described. However, the scientific knowledge in this area remains very superficial. This review evaluated the diagnostic effectiveness of various ultrasound (US) methods in the assessment of neoplastic myeloproliferation using spleen stiffness measurement (SSM). Aim: To explore the diagnostic accuracy of US techniques in assessing spleen stiffness, determining which of them may be suitable for the diagnosis of myeloproliferative diseases in adults. Methods: The review included original retrospective or prospective studies published in the last five years (2019–2024) in peer-reviewed medical journals that reported receiver operating characteristics (ROCs) for SSM and the articles concerning the relation between SSM values and neoplastic myeloproliferation. The studies were identified through PubMed searches on 1 July and 1 December 2024. Quality was assessed using the QUADAS-2 tool. Results were tabulated according to the diagnostic method separately for myeloproliferative neoplasms (MNs) and for other clinical findings. Results: The review included 52 studies providing ROCs for SSM or compatibility between operators, and five studies covering the relation between SSM values and MNs. Conclusions: Acoustic radiation force impulse (ARFI), two-dimensional shear wave elastography (2D-SWE), transient elastography (TE), and point shear wave elastography (p-SWE) are promising methods for measuring SSM that can be incorporated into the diagnosis, screening, and monitoring system in MNs. Full article

Background and Objectives: Magnesium (Mg)-based materials, such as the WE43 alloy, show potential in biomedical applications owing to their advantageous mechanical properties and biodegradability; however, their quick corrosion rate and hydrogen release restrict their general clinical utilization. This study aimed to develop a novel Mg-Zn-Ca alloy system based on WE43 alloy, evaluating the influence of Zn and Ca additions on microstructure, mechanical properties, cytocompatibility, and electrochemical behavior for potential use in biodegradable orthopedic applications. Materials and Methods: The WE43-Zn-Ca alloy system was developed by alloying standard WE43 (Mg–Y–Zr–RE) with 1.5% Zn and Ca concentrations of 0.2% (WE43_0.2Ca alloy) and 0.3% (WE43_0.3Ca alloy). Microstructural analysis was performed utilizing scanning electron microscopy (SEM) in conjunction with energy-dispersive X-ray spectroscopy (EDS), while the chemical composition was validated through optical emission spectroscopy and X-ray diffraction (XRD). Mechanical properties were assessed through tribological tests. Electrochemical corrosion behavior was evaluated using potentiodynamic polarization in a 3.5% NaCl solution. Cytocompatibility was assessed in vitro on MG63 cells using cell viability assays (MTT). Results: Alloys WE43_0.2Ca and WE43_0.3Ca exhibited refined, homogeneous microstructures with grain sizes between 70 and 100 µm, without significant structural defects. Mechanical testing indicated reduced stiffness and an elastic modulus similar to human bone (19.2–20.3 GPa), lowering the risk of stress shielding. Cytocompatibility tests confirmed non-cytotoxic behavior for alloys WE43_0.2Ca and WE43_0.3Ca, with increased cell viability and unaffected cellular morphology. Conclusions: The study validates the potential of Mg-Zn-Ca alloys (especially WE43_0.3Ca) as biodegradable biomaterials for orthopedic implants due to their favorable combination of mechanical properties, corrosion resistance, and cytocompatibility. The optimization of these alloys contributed to obtaining an improved microstructure with a reduced degradation rate and a non-cytotoxic in vitro outcome, which supports efficient bone tissue regeneration and its integration into the body for complex biomedical applications. Full article