Search Results (15)

The regeneration of bone and the repair of large segmental bone defects represent critical challenges in regenerative medicine. Natural bone tissue is an anisotropic material characterized by an intricate gradient distribution in structure, mechanical properties, and biochemical composition; this multi-dimensional heterogeneity is crucial for maintaining its physiological functions and guiding regeneration. Although tissue engineering scaffolds have demonstrated significant potential in the treatment of bone defects, homogeneous or single-gradient scaffolds often struggle to precisely recapitulate the high degree of heterogeneity and anisotropy of natural bone from the macroscopic to the microscopic level, thereby limiting their capability in repairing complex bone defects. In recent years, biomimetic gradient scaffolds—particularly those employing multi-gradient synergistic designs that integrate physical structure, biochemical composition, and mechanical properties—have emerged as a research frontier in this field due to their ability to accurately mimic the natural bone microenvironment and regulate cellular behavior. This research aims to systematically review the latest research progress in gradient scaffolds for bone tissue engineering. First, gradient characteristics of biomimetic gradient bone scaffolds are summarized; second, the design strategies for gradient scaffolds are discussed in depth, with a focus on the applications and advantages of advanced fabrication techniques, such as additive manufacturing, in constructing multi-dimensional gradient structures; finally, based on current research findings, the emerging development trends and future research directions of biomimetic gradient bone scaffolds are outlined to provide a reference for innovative breakthroughs in the field of bone tissue engineering. Full article

Sinus augmentation provides a well-established model for investigating the three-dimensional morphometry and macromolecular dynamics of bone regeneration, particularly when using biphasic calcium phosphate (BCP) graft substitutes. This case series included six biopsies from patients who underwent maxillary sinus augmentation using BCP granules composed of 30% hydroxyapatite (HA) and 70% β-tricalcium phosphate (β-TCP). Bone core biopsies were obtained at healing times of 6 months, 9 months, and 12 months. Histological evaluation yielded qualitative and quantitative insights into new bone distribution, while micro-computed tomography (micro-CT) and Raman microspectroscopy (RMS) were employed to assess the three-dimensional architecture and macromolecular composition of the regenerated bone. Micro-CT analysis revealed progressive maturation of the regenerated bone microstructure over time. At 6 months, the apical regenerated area exhibited a significantly higher mineralized volume fraction (58 ± 5%) compared to the basal native bone (44 ± 11%; p = 0.0170), as well as significantly reduced trabecular spacing (Tb.Sp: 187 ± 70 µm vs. 325 ± 96 µm; p = 0.0155) and degree of anisotropy (DA: 0.37 ± 0.05 vs. 0.73 ± 0.03; p < 0.0001). By 12 months, the mineralized volume fraction in the regenerated area (53 ± 5%) was statistically comparable to basal bone (44 ± 3%; p > 0.05), while Tb.Sp (211 ± 20 µm) and DA (0.23 ± 0.09) remained significantly lower (Tb.Sp: 395 ± 41 µm, p = 0.0041; DA: 0.46 ± 0.04, p = 0.0001), indicating continued structural remodelling and organization. Raman microspectroscopy further revealed dynamic macromolecular changes during healing. Characteristic β-TCP peaks (e.g., 1315, 1380, 1483 cm⁻¹) progressively diminished over time and were completely absent in the regenerated tissue at 12 months, contrasting with their partial presence at 6 months. Simultaneously, increased intensity of collagen-specific bands (e.g., Amide I at 1661 cm⁻¹, Amide III at 1250 cm⁻¹) and carbonate peaks (1065 cm⁻¹) reflected active matrix formation and mineralization. Overall, this case series provides qualitative and quantitative evidence that bone regeneration and integration of BCP granules in sinus augmentation continues beyond 6 months, with ongoing maturation observed up to 12 months post-grafting. Full article

Many tissues exhibit structural anisotropy, which imparts orientation-specific properties and functions. However, recapitulating the cellular patterns found in anisotropic tissues presents a remarkable challenge, particularly when using soft and wet hydrogels. Herein, we develop self-assembled anisotropic magnetic Fe₃O₄ micropatterns on polyethylene glycol hydrogels utilizing dipole–dipole interactions. Under the influence of a static magnetic field, Fe₃O₄ nanoparticles align into highly ordered structures with a height of 400–600 nm and a width of 8–10 μm. Furthermore, our layer-by-layer assembly technique enables the creation of oriented micropatterns with varying densities and heights, which can be further manipulated to form three-dimensional structures by adjusting the angle of the magnetic field. These anisotropic magnetic Fe₃O₄ micropatterns can be applied to various substrates, including treated glass slides, standard glass slides, silicon wafers, and polydimethylsiloxane. The patterned Fe₃O₄ scaffolds, modified with gold coating, effectively enhance cellular adhesion, orientation, and osteogenic differentiation of bone marrow-derived stem cells, which is crucial for effective tissue repair. Overall, this study presents an efficient strategy for constructing anisotropic Fe₃O₄ micropattern hydrogels, providing a bioactive platform that significantly enhances cellular functions. Full article

Mechanical processing of cortical bone tissue is one of the most common surgical procedures. A critical issue accompanying this processing is the condition of the surface layer, which can stimulate tissue growth and serve as a drug carrier. A comparison of the surface condition before and after orthogonal and abrasive processing was conducted to validate the influence of bone tissue’s processing mechanism and orthotropic properties on the surface topography. A cutting tool with a defined geometry and a custom-made abrasive tool was used. The bone samples were cut in three directions, depending on the orientation of the osteons. The cutting forces, acoustic emission, and surface topography were measured. The level of isotropy and the topography of the grooves showed statistical differences relative to the anisotropy directions. After orthogonal processing, the surface topography parameter Ra was determined from 1.38 ± 0.17 μm to 2.82 ± 0.32. In the case of abrasive processing, no correlation was found between the orientation of osteons and topographical properties. The average groove density for abrasive machining was below 1004 ± 0.7, and for orthogonal, it was above 1156 ± 58. Due to the positive properties of the developed bone surface, it is advisable to cut in the transverse direction and parallel to the axis of the osteons. Full article

Scaffolds are an essential component of bone tissue engineering. They provide support and create a physiological environment for cells to proliferate and differentiate. Bone allografts extracted from human donors are promising scaffolds due to their mechanical and structural characteristics. Bone microarchitecture is well known to be an important determinant of macroscopic mechanical properties, but its role at the microscopic, i.e., the trabeculae level is still poorly understood. The present study investigated linear correlations between microarchitectural parameters obtained from X-ray computed tomography (micro-CT) images of bone allografts, such as bone volume fraction (BV/TV), degree of anisotropy (DA), or ellipsoid factor (EF), and micromechanical parameters derived from micro-finite element calculations, such as mean axial strain (ε_z) and strain energy density (W_e). DAEF, a new parameter based on a linear combination of the two microarchitectural parameters DA and EF, showed a strong linear correlation with the bone mechanical characteristics at the microscopic scale. Our results concluded that the spatial distribution and the plate-and-rod structure of trabecular bone are the main determinants of the mechanical properties of bone at the microscopic level. The DAEF parameter could, therefore, be used as a tool to predict the level of mechanical stimulation at the local scale, a key parameter to better understand and optimize the mechanism of osteogenesis in bone tissue engineering. Full article

In a scaffold-based approach for bone tissue regeneration, the control over morphometry allows for balancing scaffold biomechanical performances. In this experimental work, trabecular geometry was obtained by a generative design process, and scaffolds were manufactured by vat photopolymerization with 60% (P60), 70% (P70) and 80% (P80) total porosity. The mechanical and biological performances of the produced scaffolds were investigated, and the results were correlated with morphometric parameters, aiming to investigate the influence of trabecular geometry on the elastic modulus, the ultimate compressive strength of scaffolds and MG-63 human osteosarcoma cell viability. The results showed that P60 trabecular geometry allows for matching the mechanical requirements of human mandibular trabecular bone. From the statistical analysis, a general trend can be inferred, suggesting strut thickness, the degree of anisotropy, connectivity density and specific surface as the main morphometric parameters influencing the biomechanical behavior of trabecular scaffolds, in the perspective of tissue engineering applications. Full article

With the ability to fabricate complex structures while meeting individual needs, additive manufacturing (AM) offers unprecedented opportunities for bone tissue engineering in the biomedical field. However, traditional metal implants have many adverse effects due to their poor integration with host tissues, and therefore new material implants with porous structures are gradually being developed that are suitable for clinical medical applications. From the perspectives of additive manufacturing technology and materials, this article discusses a suitable manufacturing process for ideal materials for biological bone tissue engineering. It begins with a review of the methods and applicable materials in existing additive manufacturing technologies and their applications in biomedicine, introducing the advantages and disadvantages of various AM technologies. The properties of materials including metals and polymers, commonly used AM technologies, recent developments, and their applications in bone tissue engineering are discussed in detail and summarized. In addition, the main challenges for different metallic and polymer materials, such as biodegradability, anisotropy, growth factors to promote the osteogenic capacity, and enhancement of mechanical properties are also introduced. Finally, the development prospects for AM technologies and biomaterials in bone tissue engineering are considered. Full article

Multipotent mesenchymal stem/stromal cells (MSC) are one of the crucial regulators of regeneration and tissue repair and possess an intrinsic program from self-organization mediated by condensation, migration and self-patterning. The ability to self-organize has been successfully exploited in tissue engineering approaches using cell sheets (CS) and their modifications. In this study, we used CS as a model of human MSC spontaneous self-organization to demonstrate its structural, transcriptomic impact and multipotent stromal cell commitment. We used CS formation to visualize MSC self-organization and evaluated the role of the Rho-GTPase pathway in spontaneous condensation, resulting in a significant anisotropy of the cell density within the construct. Differentiation assays were carried out using conventional protocols, and microdissection and RNA-sequencing were applied to establish putative targets behind the observed phenomena. The differentiation of MSC to bone and cartilage, but not to adipocytes in CS, occurred more effectively than in the monolayer. RNA-sequencing indicated transcriptional shifts involving the activation of the Rho-GTPase pathway and repression of SREBP, which was concordant with the lack of adipogenesis in CS. Eventually, we used an inhibitory analysis to validate our findings and suggested a model where the self-organization of MSC defined their commitment and cell fate via ROCK1/2 and SREBP as major effectors under the putative switching control of AMP kinase. Full article

Metal additive manufacturing is a powerful tool for providing the desired functional performance through a three-dimensional (3D) structural design. Among the material functions, anisotropic mechanical properties are indispensable for enabling the capabilities of structural materials for living tissues. For biomedical materials to replace bone function, it is necessary to provide an anisotropic mechanical property that mimics that of bones. For desired control of the mechanical performance of the materials, we propose a novel 3D puzzle structure with cube-shaped parts comprising 27 (3 × 3 × 3) unit compartments. We designed and fabricated a Co–Cr–Mo composite structure through spatial control of the positional arrangement of powder/solid parts using the laser powder bed fusion (L-PBF) method. The mechanical function of the fabricated structure can be predicted using the rule of mixtures based on the arrangement pattern of each part. The solid parts in the cubic structure were obtained by melting and solidifying the metal powder with a laser, while the powder parts were obtained through the remaining nonmelted powders inside the structure. This is the first report to achieve an innovative material design that can provide an anisotropic Young’s modulus by arranging the powder and solid parts using additive manufacturing technology. Full article

Dental implants’ success comprises their proper stability and adherence to different oral tissues (integration). The implant is exposed to different mechanical stresses from swallowing, mastication and parafunctions for a normal tooth, leading to the simultaneous mechanical movement and deformation of the whole structure. The knowledge of the mechanical properties of the bone and gingival tissues in normal and pathological conditions is very important for the successful conception of dental implants and for clinical practice to access and prevent potential failures and complications originating from incorrect mechanical factors’ combinations. The challenge is that many reported biomechanical properties of these tissues are substantially scattered. This study carries out a critical analysis of known data on mechanical properties of bone and oral soft tissues, suggests more convenient computation methods incorporating invariant parameters and non-linearity with tissues anisotropy, and applies a consistent use of these properties for in silico design and the application of dental implants. Results show the advantages of this approach in analysis and visualization of stress and strain components with potential translation to dental implantology. Full article

Osteochondral scaffold technology has emerged as a promising therapy for repairing osteochondral defects. Recent research suggests that seeding osteochondral scaffolds with bone marrow concentrate (BMC) may enhance tissue regeneration. To examine this hypothesis, this study examined subchondral bone regeneration in scaffolds with and without BMC. Ovine stifle condyle models were used for the in vivo study. Two scaffold systems (8 mm diameter and 10 mm thick) with and without BMC were implanted into the femoral condyle, and the tissues were retrieved after six months. The retrieved femoral condyles (with scaffold in) were examined using micro-computed tomography scans (micro-CT), and the micro-CT data were further analysed by ImageJ with respect to trabecular thickness, bone volume to total volume ratio (BV/TV) ratio, and degree of anisotropy of bone. Statistical analysis compared bone regeneration between scaffold groups and sub-set regions. These results were mostly insignificant (p < 0.05), with the exception of bone volume to total volume ratio when comparing scaffold composition and sub-set region. Additional trends in the data were observed. These results suggest that the scaffold composition and addition of BMC did not significantly affect bone regeneration in osteochondral defects after six months. However, this research provides data which may guide the development of future treatments. Full article

An efficient reliability algorithm is developed to transfer the system reliability problem to a single-component reliability problem, considering the uncertainty of loading cases and the material properties. The main difficulty is that femoral bone densities change after hip arthroplasty and, thus, the mechanical properties of the distinctive bone tissues and, therefore, the corresponding elasticity modulus and yield stress values change. Therefore, taking these changes into account during the hip prosthesis design process is strongly needed. As the bone possesses anisotropic behaviors, as the material properties in both radial and tangential directions in long bone (femur, tibia) are almost similar, the bone anisotropy is represented in this study by transversal isotropy. Two optimized formulations for yield stress against the elasticity modulus relationship are first developed and then integrated into an efficient reliability algorithm. Thus, a coupling between reliability and optimization, so-called reliability-based design optimization (RBDO), is introduced in order to control the reliability level. The proposed RBDO algorithm using optimum safety factors (OSF) takes into account the material uncertainties and leads to new stem dimensions. An in-depth numerical analysis on a cementless hip prosthesis is implemented to demonstrate the appropriateness of the proposed algorithm with the consideration of many different loading cases. The results show that the studied model can be effectively used when compared to previous works, which concerns the changes in both geometry and material properties. Full article

Bone metastasis is one of the most intractable bone diseases; it is accompanied with a severe mechanical dysfunction of bone tissue. We recently discovered that the disorganized collagen/apatite microstructure in cancer-bearing bone is a dominant determinant of the disruption of bone mechanical function; disordered osteoblast arrangement was found to be one of the principal determinants of the deteriorated collagen/apatite microstructure. However, the precise molecular mechanisms regulating the disordered osteoblast arrangement triggered by cancer invasion are not yet understood. Herein, we demonstrate a significant disorganization of bone tissue anisotropy in metastasized bone in our novel ex vivo metastasis model. Further, we propose a novel mechanism underlying the disorganization of a metastasized bone matrix: A dynamic collision behavior between tumor cells and osteoblasts disturbs the osteoblast arrangement along the collagen substrate. Full article

Additive Manufacturing (AM) methods are generally used to produce an early sample or near net-shape elements based on three-dimensional geometrical modules. To date, publications on AM of metal implants have mainly focused on knee and hip replacements or bone scaffolds for tissue engineering. The direct fabrication of metallic implants can be achieved by methods, such as Selective Laser Melting (SLM) or Electron Beam Melting (EBM). This work compares the SLM and EBM methods used in the fabrication of titanium bone implants by analyzing the microstructure, mechanical properties and cytotoxicity. The SLM process was conducted in an environmental chamber using 0.4–0.6 vol % of oxygen to enhance the mechanical properties of a Ti-6Al-4V alloy. SLM processed material had high anisotropy of mechanical properties and superior UTS (1246–1421 MPa) when compared to the EBM (972–976 MPa) and the wrought material (933–942 MPa). The microstructure and phase composition depended on the used fabrication method. The AM methods caused the formation of long epitaxial grains of the prior β phase. The equilibrium phases (α + β) and non-equilibrium α’ martensite was obtained after EBM and SLM, respectively. Although it was found that the heat transfer that occurs during the layer by layer generation of the component caused aluminum content deviations, neither methods generated any cytotoxic effects. Furthermore, in contrast to SLM, the EBM fabricated material met the ASTMF136 standard for surgical implant applications. Full article

The anisotropic microstructure of bone tissue is crucial for appropriate mechanical and biological functions of bone. We recently revealed that the construction of oriented bone matrix is established by osteoblast alignment; there is a quite unique correlation between cell alignment and cell-produced bone matrix orientation governed by the molecular interactions between material surface and cells. Titanium and its alloys are one of the most attractive materials for biomedical applications. We previously succeeded in controlling cellular arrangement using the dislocations of a crystallographic slip system in titanium single crystals with hexagonal close-packing (hcp) crystal lattice. Here, we induced a specific surface topography by deformation twinning and dislocation motion to control cell orientation. Dislocation and deformation twinning were introduced into α-titanium polycrystals in compression, inducing a characteristic surface structure involving nanometer-scale highly concentrated twinning traces. The plastic deformation-induced surface topography strongly influenced osteoblast orientation, causing them to align preferentially along the slip and twinning traces. This surface morphology, exhibiting a characteristic grating structure, controlled the localization of focal adhesions and subsequent elongation of stress fibers in osteoblasts. These results indicate that cellular responses against dislocation and deformation twinning are useful for controlling osteoblast alignment and the resulting bone matrix anisotropy. Full article