Search Results (2,312)

Restoration of the osteochondral unit remains a major challenge in regenerative orthopaedics, largely due to the limited intrinsic healing capacity of articular cartilage and the complex, multilayered nature of the cartilage–bone interface. Osteochondral regeneration must accommodate differences in cellular composition, vascularization, metabolic demand, and mechanical properties between cartilage and bone, while simultaneously recreating a stable, functional interface. While exogenous mesenchymal stem cell (MSC) therapies have dominated the field, their clinical translation has been hindered by donor variability, phenotypic instability, logistical complexity, and inconsistent long-term outcomes. Resident stem cells from sources such as articular cartilage, bone marrow, periosteum, synovium, synovial fluid, and adipose tissue (infrapatellar fat pad) can act as potential targets for in situ osteochondral regenerative therapies. Joint-resident MSCs are adapted to the biomechanical and biochemical environment of the joint and may therefore represent a promising cell source for osteochondral regeneration; however, much of the supporting evidence remains preclinical. Effective osteochondral repair depends on the precise orchestration of stem cell recruitment, maintenance of chondrogenic phenotypes, induction of osteogenic differentiation in the subchondral compartment, and modulation of local immune responses. Patient-specific factors, including age, inflammatory status, and the severity of osteoarthritis, can significantly influence the regenerative potential of resident MSC populations and should therefore guide biomaterial design strategies. The proposed niche-by-design framework integrates stem cell biology with advanced biomaterial engineering, offering a rational roadmap for developing next-generation therapies that promote endogenous osteochondral regeneration through targeted activation of joint-resident progenitor cells. Full article

An innovative strategy for collagen self-assembly with accelerated intra and extrafibrillar mineralisation is introduced to generate bone scaffolds with biomimetic properties. This method, termed Rapid Fibrillogenic Mineralisation (RFM), leverages coprecipitation with 10× Simulated Body Fluid (10× SBF) during fibril formation to maximise nucleation, particularly within intrafibrillar zones at molecular termini. Densification is achieved within minutes via plastic compression driven by capillary action, producing bone-like scaffold density without compromising the collagen matrix. Transmission electron microscopy confirms intrafibrillar hydroxyapatite crystals within 15 min, while X-ray diffraction demonstrates distinct HA peaks across groups. Scanning electron microscopy verified extrafibrillar mineralisation after 4 h, with saturation by 6 h, yielding ‘nanoflower’ crystal clusters. Infrared spectra showed increased carbonate content over time, indicating lattice substitutions characteristic of natural bone. Enhanced mineralisation translated into significant mechanical gains as Dynamic Mechanical Analysis revealed compressive moduli approaching cancellous bone (up to 283 ± 31 MPa). In addition, a decrease in the piezoelectric coefficient occurs with increased mineralisation process, highlighting the effects of mineral inclusions on collagen fibre composition and anisotropy. Biologically, mineralised scaffolds supported cellular growth compared to collagen controls. RFM thus enables rapid, reproducible fabrication of biomimetic bone scaffolds that closely emulate native mineralisation patterns and mechanical behaviour. Beyond offering a practical route for scaffold production in tissue engineering, the process also provides new insights into bone physiology and in vitro modelling. By reshaping collagen into a synthetic echo of nature’s bone, RFM establishes a rapid approach for designing functional biomaterials with translational potential. Full article

Hydroxyapatite (HA) is widely used in biomedical applications due to its biocompatibility and chemical similarity to the mineral phase of bone; however, its low mechanical strength limits its structural use. In this work, HA ceramics with different Mg additions (0, 0.5, 1, 3, 5, and 10% by weight) were prepared using the powder processing technique. The mixtures were homogenized, conformed and sintered at 1100 °C. The incorporation of intermediate Mg concentrations produced an increase in fracture toughness compared to pure HA. The best mechanical performance was obtained with the formulation containing 5% Mg by weight, achieving a hardness of 319 HV, a porosity of 12.92% and a fracture toughness of 4.06 MPa·m^0.5, comparable to those reported for human cortical bone, indicating its potential for applications in moderately loaded bone implants. The findings indicate that magnesium functions as a reinforcing component in the ceramic matrix, mitigating critical defects and thereby contributing to the improved toughness of Mg-containing hydroxyapatite ceramics. The polarization resistance results show that the incorporation of low fractions by weight of magnesium (1% Mg) adjusts the electrochemical behavior of the material, while higher increases in its concentration cause a deterioration of this property. Full article

For critical-sized bone defects, bioactive implants are indispensable. Although advanced three-dimensional (3D) printing technology enables the precise manufacturing of customized bone scaffolds, implant-associated infections (IAIs) remain a significant clinical challenge. Moreover, traditional passive antibacterial coatings often face problems such as uncontrolled release of antibacterial agents and insufficient long-term antibacterial efficacy. This review elaborates on the transformation of antibacterial strategies in the field of bone tissue engineering (BTE) from “passive” to “smart responsive” modes. We summarize the endogenous (such as pH, temperature, reactive oxygen species (ROS), and enzyme) and exogenous (such as light, microwave, and ultrasound) response systems. Notably, the ultrasound-driven strategy is highly emphasized due to its outstanding deep tissue penetrability and dual functional characteristics: it can not only eliminate stubborn biofilms through the sonodynamic effect by generating ROS, but also promote osteogenesis through the piezoelectric effect. Additionally, we also discuss the recent progress of artificial intelligence (AI) in the field of bone scaffold manufacturing. AI-driven algorithms help to rapidly optimize complex scaffold structures and accurately predict their mechanical properties, thereby effectively avoiding the inefficiencies brought about by the traditional “trial and error” method. In conclusion, combining AI-assisted manufacturing technology with smart responsive antibacterial strategies opens up a highly promising frontier field for the development of personalized and infection-free bone implants. Full article

Macrophage membrane-coated nanoparticles (MMNPs) are an emerging class of biomimetic nanoplatforms that combine the immune-regulatory functions of macrophages with the structural versatility of synthetic nanoparticles (NPs). By retaining key membrane proteins and receptors, MMNPs exhibit natural targeting capabilities, immune interactions, and inflammatory site homing, making them promising tools for immunomodulation and targeted therapy. This review summarizes macrophage biology relevant to immune regulation and discusses how nanoparticle core properties, including size, surface charge, composition, and mechanical characteristics, influence membrane coating efficiency, stability, and biological performance. Current fabrication and characterization strategies for MMNPs are also discussed. Particular emphasis is placed on the therapeutic applications of MMNPs in inflammatory disorders, tissue regeneration, and oral and dental implant-related applications. Recent studies demonstrate that MMNPs can modulate macrophage polarization, sequester pro-inflammatory cytokines, remodel the immune microenvironment, and promote tissue repair and bone regeneration, highlighting their potential to improve implant integration and reduce inflammation-associated implant failure. Despite these promising advances, challenges remain regarding large-scale manufacturing, membrane preservation, reproducibility, and long-term biosafety. Continued interdisciplinary research in nanotechnology, immunology, and biomaterials engineering is expected to accelerate the clinical translation of MMNPs for regenerative and immunomodulatory therapies. Full article

Polyetheretherketone (PEEK) is a favorable material in bone tissue engineering due to its excellent mechanical properties and biocompatibility. However, as PEEK is biologically inert, this study introduced hydroxyapatite (HA) and graphene oxide (GO) to modify PEEK, and PEEK/GO/HA composites were prepared via compression molding and sintering. Molecular dynamics simulation results indicated that the Young’s modulus of the composite increased with rising HA content. The trends in the bulk modulus and shear modulus suggested a possible downward trend around HA contents of 10 wt% and 20 wt%; this may be attributed to the polarity mismatch between HA and PEEK, as well as the composite preparation process. The thermal conductivity of the composites exhibited a similar trend, with the thermal conductivity decreasing until the HA content reached 30 wt% due to interfacial thermal resistance between PEEK and HA. Concurrently, in vitro cell culture experiments were conducted on the precursor powder mixture to investigate the effect of the composition ratio on biological properties. The results indicated that cell viability was higher when the HA content was 30 wt%. This demonstrates the significant potential of PEEK/GO/HA composites in the field of bone tissue engineering. Full article

Guided Bone Regeneration (GBR) is a pivotal technique in dental and orthopedic applications for regenerating bone in areas of deficiency. Natural polymers such as collagen, chitosan, alginate, and gelatin have emerged as essential materials in GBR due to their biocompatibility, biodegradability, and bioactivity. These polymers not only provide a scaffold for bone regeneration but also support cellular adhesion, proliferation, and differentiation. Despite their benefits, challenges such as variable degradation rates, insufficient mechanical strength, and limited bioactivity hinder their optimal clinical use. To address these limitations, ongoing research focuses on enhancing the properties of natural polymers. Composite materials combining fast- and slow-degrading polymers are being developed to achieve consistent degradation rates. Surface modifications, including nanoscale texturing and growth factor coatings, are improving bioactivity. Nanotechnology further enhances the structural and therapeutic potential of GBR materials, while advancements in 3D bioprinting enable the creation of customized scaffolds with precise architecture. These innovations aim to bridge the gap between biological compatibility and clinical functionality, making natural polymers more adaptable and effective in GBR. This review highlights the mechanisms, challenges, and advancements in natural polymers for GBR, emphasizing their potential to transform bone regeneration into a more reliable and patient-centered approach. Full article

Titanium and its alloys are cornerstone biomaterials due to their high strength-to-weight ratio, excellent fatigue and corrosion resistance, biocompatibility, and ability to osseointegrate with bone. Their relatively low elastic modulus compared to stainless steels and Co–Cr alloys further enhances their suitability for biomedical applications. Performance is continually improved through alloy design (tailoring α and β phases), advanced manufacturing methods such as CNC machining and additive manufacturing, and surface engineering approaches. In particular, the formation of a stable TiO₂ layer promotes corrosion resistance and cell attachment, while coatings and nanotexturing enhance osseointegration and provide antibacterial functionality. These attributes enable widespread use in orthopedic, dental, and cardiovascular implants. Emerging developments include smart implants with embedded sensors, multifunctional surfaces, and data-driven alloy design, aiming to further optimize mechanical performance, biological response, and long-term reliability. This review summarizes the processing techniques, properties, applications, and recent advances in titanium-based biomaterials. Full article

Background/Objectives: Trabecular bone exhibits brittle behaviour governed by microscale deformation and damage, yet quantifying crack progression is difficult because classical fracture-mechanics approaches do not apply to architecturally discontinuous porous tissue. This pilot study evaluates whether synchrotron X-ray computed tomography (XCT) combined with digital volume correlation (DVC) can provide a practical, geometry-normalised approach for quantifying crack-opening behaviour in human trabecular bone. Methods: Semicylindrical specimens from femoral heads of hip-fracture donors (n = 5) and non-fracture controls (n = 5) underwent stepwise three-point bending during XCT imaging. Full-field displacement maps were used to measure crack mouth opening displacement (CMOD), crack length (a), and their ratio CMOD/a, used here as a geometry-normalised comparative descriptor of brittle response rather than an intrinsic material property. Automated phase-congruency crack detection (PCCD) was compared with manual measurement. Results: XCT–DVC resolved three-dimensional displacement discontinuities during crack initiation and propagation in all specimens. Hip-fracture donors exhibited significantly lower critical crack-opening ratios (CMOD/a)* than Controls (median 0.31 vs. 0.47; p = 0.008) and reached instability at lower applied loads. Total crack extension (Δa*) was similar between groups. Automated crack tracking using phase-congruency-based segmentation showed excellent agreement with manual measurements (r² = 0.98), supporting reliable extraction of crack geometry from DVC displacement fields. Conclusions: In this small pilot sample, XCT–DVC provided a feasible, geometry-normalised approach for comparing crack-opening behaviour where classical fracture-mechanics parameters cannot be applied. The close agreement between automated and manual crack measurements supports the reproducibility of the displacement-based measurement pipeline. The lower critical CMOD/a in hip-fracture specimens may indicate a more brittle comparative response. However, given the small sample, differing sex distribution, and lower bone volume fraction in the hip-fracture group, these findings are preliminary and require confirmation in larger cohorts. Establishing whether the observed difference reflects intrinsic tissue brittleness, architectural factors, or both is an important objective for future work in microstructure-matched cohorts. Full article

Lattice structures have gained particular interest in the last years, because of the spread of Additive Manufacturing, which allowed their production with ease. These structures may be used as functionally graded materials for lightweighting in structural components, or they can be tailored to match the mechanical properties of bone tissue for orthopedic implants. To reduce the computational time and costs of structural simulation and optimization, this study presents a numerical homogenization to determine the main elastic constants of the BCCz lattice, over its relative density. Numerical simulations are carried out on a lattice with a nominal geometry, made from a homogeneous isotropic material. Results present charts and interpolating functions of the elastic constants of the lattice, over its relative density, that may help the designer in tailoring the lattice structure to the desired applications. Results show that the BCCz presents a substantial influence of the load direction on the mechanical properties, with the z direction showing superior properties than the transverse direction. This makes the BCCz lattice ideal for those structures where the main load directions are easily predictable. Full article

Sickle cell disease (SCD), the most common inherited blood disorder in the United States, affects approximately 100,000 individuals annually. A major complication of SCD is sickle cell bone disease, which results in substantial bone loss comparable to osteoporosis. Previous work showed that treatment with GBT1118, a sickle hemoglobin polymerization inhibitor, improved bone formation and reduced bone resorption in humanized SCD mice. However, its effects on bone material and mechanical properties were unknown. To address this, four-month-old control and SCD mice were fed vehicle or GBT1118 chow for two months. Hematocrit levels, significantly reduced in SCD mice of both sexes, were restored by GBT1118 treatment, confirming its efficacy in improving anemia. Raman spectroscopy revealed increased mineral-to-organic matrix ratios in SCD femurs of both sexes and elevated carbonate-to-phosphate ratios in males, none of which were altered by GBT1118. Mechanical testing showed decreases in ultimate stress and Young’s modulus in female SCD femurs, with no significant differences in males nor rescue by GBT1118. Thus, while GBT1118 improved hematological parameters, it failed to restore the impaired bone material properties observed in SCD mice, highlighting the need for additional therapeutic strategies to address bone fragility in sickle cell disease. Full article

3D-printed hydrogel scaffolds have emerged as important platforms in tissue engineering and regenerative medicine owing to their extracellular matrix-like three-dimensional hydrated networks, tunable physicochemical properties, and ability to spatially organize cells, bioactive factors, and scaffold architectures. Early studies mainly focused on the printability, shape fidelity, and biocompatibility of hydrogel inks, whereas current research has gradually shifted toward the construction of bioactive scaffolds with tissue-specific functions. Because different tissues exhibit distinct requirements in terms of mechanical properties, cellular microenvironment, vascularization, innervation, degradation behavior, and functional maturation, the design of 3D-printed hydrogel scaffolds should comprehensively consider material composition, printing strategy, biofactor delivery, and tissue-specific functional demands. In this review, we focus on the transition from printability to biofunctionality and systematically summarize recent advances in 3D-printed hydrogel scaffolds for multi-tissue engineering. Particular emphasis is placed on regenerative applications of 3D-printed hydrogel scaffolds in bone, cartilage, vascular, neural, and skin tissue engineering. Finally, we discuss the major challenges associated with 3D-printed hydrogel scaffolds and further highlight future directions. This review aims to provide a systematic reference for the functional design and application of 3D-printed hydrogel scaffolds in multi-tissue engineering. Full article

Background: Degenerative joint diseases are a major cause of disability and drive the increasing demand for joint arthroplasty. Long-term prosthesis success depends on rapid and stable bone–implant integration, which is influenced by the osteo-inductive and osteo-conductive properties of implant materials. Chromium–cobalt (CrCo) and titanium (Ti) alloys are widely used in reconstructive orthopedics, but direct comparative data on their biological performance, particularly for trabecular titanium (T-Ti), remain limited. This study aimed to directly compare the biocompatibility and osteogenic potential of CrCo and T-Ti using human mesenchymal stromal cells (MSCs). Methods: Human MSCs were characterized by immunophenotyping and cultured on CrCo and T-Ti scaffolds under control and osteogenic conditions for up to 28 days. Cell adhesion and morphology were assessed by scanning electron microscopy. Proliferation and viability were quantified, and osteogenic differentiation was evaluated using alkaline phosphatase activity, calcium deposition assays, and gene expression profiling of osteogenic markers. Results: Both materials supported MSC adhesion and proliferation, confirming cytocompatibility. Under control conditions, T-Ti significantly increased alkaline phosphatase activity and osteogenic gene expression. Under osteogenic stimulation, T-Ti accelerated differentiation and mineralized matrix deposition. CrCo exhibited limited stimulation of the osteogenic-supportive microenvironment and delayed differentiation responses. Conclusions: Trabecular titanium, in terms of morphology and topology, provides a biologically active scaffold that both induces and conducts osteogenic differentiation of human MSCs, whereas CrCo acts primarily as a mechanically optimized but biologically passive material. These findings support the use of trabecular titanium at bone-contact interfaces in joint prostheses to enhance osteointegration and potentially improve long-term implant stability. Full article

Background/Objectives: Ankylosing Spinal Disorders (ASDs) encompass a heterogeneous group of rheumatic diseases characterized by progressive ankylosis of the axial skeleton, including Ankylosing Spondylitis (AS), Diffuse Idiopathic Skeletal Hyperostosis (DISH), and Non-Radiographic Axial Spondyloarthritis (nr-AxSpA). Spinal ankylosis profoundly alters the biomechanical properties of the vertebral column, transforming it into a rigid long-bone equivalent and dramatically increasing fracture risk even after low-energy trauma. Once a fracture occurs, the long lever arm created by the ankylosed segments generates enormous mechanical stress at the fracture site, making surgical stabilization mandatory in the vast majority of cases. Long posterior instrumentation is the treatment of choice; however, no consensus exists regarding the optimal number of instrumented levels. The aim of this study is to clinically and radiologically evaluate long posterior instrumentation in the 3 + 3 (3 proximal and 3 caudal screws), 3 + 2 (3 proximal and 2 caudal screws), or 2 + 2 (2 proximal and 2 caudal screws) configuration for the treatment of traumatic ASD thoracolumbar vertebral fractures, in terms of implant failure, infection rate, and mortality. Methods: Between 2018 and 2023, 65 consecutive patients with ASD-related thoracolumbar vertebral fractures were treated at our institution. After applying pre-defined inclusion and exclusion criteria, 37 patients were enrolled. Patients were retrospectively divided into three groups according to the posterior arthrodesis configuration (notation indicates number of instrumented vertebral levels proximal + distal to the fracture: 3 + 3, 3 + 2, or 2 + 2). Radiological outcomes were assessed for loosening, screw cut-out, and implant breakage. Infection and mortality rates within 3 months from surgery were evaluated as secondary endpoints. Statistical analysis was performed using the Fisher exact test (significance set at p < 0.05). Results: Thirty-seven patients (28 males and 9 females; mean age 77 ± 7.3 years) were included, with a mean follow-up of 30 ± 5.3 months. Instrumentation configurations were as follows: 23 (3 + 3), 5 (3 + 2), and 9 (2 + 2). Three implant failures (8.1%) and four infections (10.8%) were recorded. Eleven patients died within 3 months of surgery. A statistically significant difference was found between instrumentation length and mechanical complications (p = 0.0468), while no significant difference was observed for infection (p = 1) or mortality rate (p = 0.137). Conclusions: In this exploratory retrospective cohort, the 3 + 3 configuration was associated with the lowest observed rate of implant failure in ASD thoracolumbar fractures, suggesting a potential mechanical advantage over shorter constructs that warrants confirmation in larger prospective studies. No significant correlation was found between instrumentation length and infection rate or early mortality. Prospective, multicentre studies with larger cohorts are warranted to establish definitive guidelines for instrumentation length in this challenging patient population. 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