Search Results (452)

Dental implants have become common for restoring function and aesthetics after edentulism, with titanium (Ti) remaining the most widely used material due to its excellent mechanical properties and biocompatibility. Despite their clinical success, long-term performance is strongly influenced by surface characteristics, which regulate osseointegration and susceptibility to bacterial colonisation. Consequently, surface modification approaches have become critical strategies to enhance implant stability, bioactivity and longevity. This review critically evaluates conventional, advanced, and hybrid surface modification strategies. Subtractive methods, such as sandblasting and acid etching, increase microroughness (Ra 1.5–3 μm), enhancing osteoblast attachment and differentiation, but may promote bacterial adhesion and surface contamination. Combined treatments like SLA and SLActive generate hierarchical micro–nano topographies, improving protein adsorption, early-stage osteoblast proliferation (up to 2-fold), and clinical stability. Laser ablation and photofunctionalisation further modulate surface chemistry and wettability, accelerating osseointegration and epithelial cell adhesion. Coating approaches, including layer-by-layer self-assembly, nanospray drying, plasma spraying, and piezoelectric nanocomposites, introduce antimicrobial activity (>95% reduction in Escherichia coli or Staphylococcus aureus) and enhanced osteogenic differentiation with mechanical stability, with adhesion values reaching 49 MPa. Hybrid techniques such as sol–gel, hydrothermal, and anodisation provide controlled topography, chemical composition, and bioactivity, promoting early bone-to-implant contact (BIC increase of 10%–25%) in preclinical models. Notwithstanding promising in vitro and in vivo outcomes, variability in processing parameters and limited standardisation restrict large-scale clinical translation. Overall, contemporary Ti surface engineering emphasises a synergistic balance of topography, chemistry, wettability, and hierarchical structuring to optimise biological performance for dental implant applications. Full article

Circulating tumour DNA (ctDNA) assays are increasingly applied in haematological malignancies for non-invasive genotyping, quantitative response assessment, measurable residual disease (MRD) detection, and relapse surveillance, often complementing bone marrow-based testing and, in selected scenarios, potentially reducing its frequency. Yet, translating ctDNA results into comparable clinical decisions across laboratories, platforms, and time remains challenging because ctDNA measurements are influenced by the definition of the measurand (for example, variant allele fraction versus mutant molecules per mL), pre-analytical variables, end-to-end workflow losses, and lineage-specific confounders such as clonal haematopoiesis of indeterminate potential (CHIP), therapy-related clonal haematopoiesis, and compartmental disease (marrow, plasma, cerebrospinal fluid, extramedullary sites). This review proposes a harmonisation framework for haematological ctDNA based on three linked concepts—metrological traceability, which connects reported values to reference systems with stated uncertainty, commutability, which ensures that reference materials behave like patient specimens across diverse workflows and fit-for-purpose reference materials that support calibration, and quality control, external quality assessment, and cut-off setting for intended uses such as early molecular response in large B-cell lymphoma, molecular MRD in acute myeloid leukaemia, and deep response monitoring in multiple myeloma. This framework is accompanied by harmonised CHIP-aware reporting rules for settings without matched cellular DNA and practical change-control/bridging strategies to preserve clinical decision thresholds when platforms or bioinformatic pipelines evolve. Full article

Nanostructured calcium phosphate-based (CaP) biocomposites have proven to be ideal candidates for the creation of multifunctional systems with applications in biomedicine. This review presents a critical and integrative overview of recent advances in the synthesis of CaP nanocomposites with applications in bone tissue regeneration. An analysis of calcium phosphate-based nanocomposites is thus provided by correlating their composition, synthesis routes and biological properties, guiding the rational development of next-generation biomaterials for bone tissue engineering. The first section presents calcium phosphates, such as hydroxyapatite (HAp) or β-tricalcium phosphate (β-TCP), used in the preparation of nanocomposite materials. Next, the main biocomposite materials are analyzed as a result of the functionalization of calcium phosphates by metal ion substitutions or by the addition of polymers, bioglass or metal additives. Thus, biomaterials with excellent properties in applications such as tissue engineering have been obtained. The synergistic effect of materials in the composition of biocomposites favored the improvement of properties such as bioactivity, mechanical strength, antimicrobial activity, structure and porosity. Beyond classical osteoconductivity, CaP-based nanocomposites demonstrate a broad spectrum of biological activities like immunomodulatory effects, pro-healing signaling, anti-inflammatory pathways, antibacterial and antifungal mechanisms, and capabilities for precise drug delivery or theranostic applications. Full article

Three-dimensional (3D) bioprinting has rapidly emerged as a transformative technology at the interface of biomedical engineering and regenerative medicine. By enabling the spatially controlled deposition of living cells, biomaterials, and bioactive molecules, it offers an unprecedented potential to fabricate functional tissues and potentially whole organs in the future. This review explores recent advances in bioprinting materials, processes, and applications, emphasizing the integration of bioinks, printing methods, and mechanical design principles that underpin tissue functionality. Natural and synthetic biomaterials such as hydrogels (e.g., collagen, alginate), polyethylene glycol (PEG), and polyesters like PLGA are evaluated in terms of biocompatibility, printability, and degradation behavior. Key bioprinting modalities, including extrusion, inkjet, and laser-assisted bioprinting, are compared based on printing resolution, cell viability, and scalability. Structural considerations such as scaffold architecture, mechanical stability, and biomimetic design are discussed in relation to native tissue mechanics and requirements. The review also surveys emerging applications in tissue engineering (e.g., bone, cartilage, skin replacements), organ-on-a-chip systems for drug testing, and patient-specific implants, while addressing persistent challenges such as standardization of biofabrication, regulatory and ethical considerations, and manufacturing scale-up. Finally, future trends, including the integration of artificial intelligence (AI) and robotic automation, multi-material and four-dimensional (4D) bioprinting, and the maturation of personalized bioprinting strategies, are highlighted as pathways toward more autonomous and clinically relevant bioprinting systems. Collectively, these developments signify a paradigm shift in how biological constructs are designed and manufactured, bridging the gap between laboratory research and clinical translation. Full article

Background: Post-extraction alveolar ridge is an important factor affecting dental implant restoration. Among myriads of bone grafting materials, dentinal grafts are gaining faster popularity among clinicians. Unlike conventional xenografts derived from animal sources, these autogenous materials may offer advantages in terms of biocompatibility and cost. Objective: This article aims to compare their performance with other commonly used materials, like xenografts, or natural blood clots and to examine whether they could maintain bone quality and quantity during socket healing with better properties than the rest of the graft materials in terms of implants success rate. Methods: This search was conducted in multiple medical databases (PubMed/MEDLINE, Scopus, Cochrane Library, Embase, and Google Scholar) for studies published between 2015 and 2025. This search focused exclusively on randomized controlled trials. The study quality was assigned by using the Cochrane Risk of Bias 2 tool, performing statistical pooling of results using random-effects meta-analysis when appropriate. Results: Eight randomized controlled trials involving 249 patients and 281 bone graft sites were selected according to inclusion and exclusion criteria. Dentinal grafts produced significant increase in formation of new bone compared to xenografts (12.4% greater, 95% CI: 6.8–18.0%, p < 0.001). The grafts also resorbed more completely, leaving less foreign material behind (8.6% less residual material, p < 0.001). Importantly, implants placed in bone preserved with dentinal grafts showed comparable stability and success rates to those in bone treated with xenografts. When compared to allowing sockets to heal naturally, dentinal grafts dramatically reduced bone loss by 60–70% horizontally and 65–75% vertically. Remarkably only minor complications were observed (2.2%), with no serious adverse events across all studies. Conclusions: Our analysis indicates that dentinal grafts represent a viable and potentially superior alternative to conventional xenografts for not only preserving alveolar bone after tooth extraction but also in any existing bone defects. The evidence particularly supports using partially demineralized preparations. These materials demonstrate excellent biocompatibility, produce good bone quality, and offer cost advantages. Full article

This finite element study compared the effects of prosthetic superstructure material and supporting implant number on stresses in implants, multiunit abutments, and restorations, and on peri-implant bone strains under bruxism-like loading. Two posterior mandibular models representing missing left FDI 34–36 were generated: a 2-implant configuration (implants at 34 and 36) and a 3-implant configuration (implants at 34, 35, and 36), each restored with a three-unit implant-supported fixed bridge. For each configuration, three superstructure materials were simulated: cobalt–chromium (Co–Cr), polyetheretherketone (PEEK), and monolithic zirconia (MZ). Static parafunctional loads were applied as a 500 N oblique load (30° to the implant long axis; 125 N to each buccal cusp) and a 1000 N vertical load applied to the central fossae. Cortical bone generally exhibited higher strain than trabecular bone, and the maximum cortical principal strain under vertical loading averaged approximately 5800 μɛ. The highest implant von Mises stress occurred in the first molar implant of the 2-implant MZ model under oblique loading, while the maximum under vertical loading was 236 MPa (also 2-implant MZ). Prosthetic peak stresses reached 184 MPa under vertical loading (3-implant PEEK composite–veneered model) and 233 MPa under oblique loading (2-implant MZ), with a minimum of 51 MPa in the 3-implant PEEK framework under vertical loading. Overall, increasing implant number reduced the stress/strain values, and MZ showed comparatively higher stress and strain levels. Full article

Maxillofacial skeletal reconstruction presents significant challenges due to anatomical complexity, functional requirements, and aesthetic demands. Traditional materials such as titanium and autogenous bone grafts have limitations, prompting interest in Polyetheretherketone (PEEK), a versatile thermoplastic polymer with advantages like biocompatibility, radiolucency, and elasticity similar to human bone. This multi-year case series evaluates the clinical outcomes of PEEK implants used in 56 cases on 53 patients for maxillofacial reconstruction, primarily for trauma (44 patients) and deformity (9 patients). PEEK implants were applied to various facial regions including the orbit, zygoma, mandible, and maxilla. The majority of surgeries utilised virtual surgical planning. Patient-specific implants were fabricated using 3D imaging technologies, allowing customisation for optimal fit and functionality. The mean patient age was 37 years with a split of 37 to 16 females. Some complications were noted such as infection and paraesthesia. However, the majority of patients experienced positive outcomes. The findings support PEEK implants as a safe, effective, and adaptable material for maxillofacial surgery, with potential for further advancements in material properties and surgical technologies to improve long-term outcomes. Full article

Background/Objectives: Autologous dentin matrix (ADM) has been suggested as a biologically plausible biomaterial for alveolar bone regeneration after tooth extraction. However, clinical evidence regarding its biological activity and early healing outcomes is limited. This exploratory, randomized controlled pilot study aimed to descriptively assess early alveolar healing patterns and bone morphogenetic protein 4 (BMP4) expression following tooth extraction using ADM compared with other grafting approaches. Methods: Patients requiring tooth extraction were allocated to one of four groups: ADM, xenograft, ADM combined with platelet-rich fibrin, and a graft-free control group. Histological and immunohistochemical analyses were performed four months after extraction to descriptively assess cellular features of healing and BMP4 expression. The trial was registered at the Brazilian Registry of Clinical Trials (ReBEC; RBR-24mdgrf) and conducted under prior ethics committee approval. Results: BMP4 expression was detected in 67.9% of the analyzed histological fields, predominantly localized in osteocytic, osteoblastic, and medullary areas. Although descriptive differences in BMP4-positive fields were observed among the groups, no statistically significant differences were identified between the groups. Histological evaluation revealed an active cellular environment across all treatment modalities, consistent with early post-extraction healing. No adverse events related to surgical procedures or grafting materials were reported during the study period. Conclusions: Within the limitations of this pilot randomized clinical trial, ADM exhibited consistent biological behavior during early post-extraction alveolar healing. The observed BMP4 expression likely reflects a general physiological healing response rather than a material-specific effect. This finding supports the biological plausibility of dentin-derived grafts as osteoconductive biomaterials. These findings are hypothesis-generating, and larger, adequately powered randomized clinical trials with standardized molecular and histological assessments are required to determine their clinical relevance. Full article

Background: Guided Bone Regeneration (GBR) relies on barrier membranes, for which polylactic acid (PLA) and its copolymer poly(lactic-co-glycolic acid) (PLGA) are promising biodegradable polymers. However, their inherent hydrophobicity limits biological performance, and the evidence regarding how specific modifications affect key human cell types, particularly osteoblasts and fibroblasts, remains scattered. Methods: A systematic review was conducted to synthesize the in vitro evidence on the response of primary human osteoblasts and fibroblasts to polylactic acid-based materials. Following a pre-registered protocol (10.17605/OSF.IO/CE8KB), a comprehensive search was performed across four major databases, and the risk of bias in the included studies was assessed using an adapted OHAT tool. Results: Twenty-six studies were included, which showed that polylactic acid-based materials have limited bioactivity, and their modification significantly improves cellular responses. The incorporation of bioceramics and growth factors, or alterations in surface topography, notably enhanced osteogenic differentiation and mineralization in osteoblasts. For gingival fibroblasts, topographical modifications like micro-grooves guided cell alignment and modulated proliferation. Conclusions: Native polylactic acid-based materials display limited bioactivity. However, functionalization through bioceramics incorporation, growth factor delivery, and surface topographical modification is crucial for transforming them into bioactive scaffolds capable of achieving the dual biofunctionality required for successful GBR. Full article

This study aims to demonstrate the feasibility of ultrashort echo time (UTE)-based susceptibility source separation for musculoskeletal (MSK) imaging, enabling discrimination between diamagnetic and paramagnetic tissue components, with a particular focus on hemophilic arthropathy (HA). Three key techniques were integrated to achieve UTE-based susceptibility source separation: Iterative decomposition of water and fat with echo asymmetry and least-squares estimation for B0 field estimation, projection onto dipole fields for local field mapping, and χ-separation for quantitative susceptibility mapping (QSM) with source decomposition. A phantom containing varying concentrations of diamagnetic (CaCO₃) and paramagnetic (Fe₃O₄) materials was used to validate the method. In addition, in vivo UTE-QSM scans of the knees and ankles were performed on five HA patients using a 3T clinical MRI scanner. In the phantom, conventional QSM underestimated susceptibility values due to the mixed-source cancelling the effect. In contrast, source-separated maps provided distinct diamagnetic and paramagnetic susceptibility values that correlated strongly with CaCO₃ and Fe₃O₄ concentrations (r = −0.99 and 0.95, p < 0.05). In vivo, paramagnetic maps enabled improved visualization of hemosiderin deposits in joints of HA patients, which were poorly visualized or obscured in conventional QSM due to susceptibility cancellation by surrounding diamagnetic tissues such as bone. This study demonstrates, for the first time, the feasibility of UTE-based quantitative susceptibility source separation for MSK applications. The approach enhances the detection of paramagnetic substances like hemosiderin in HA and offers potential for improved assessment of bone and joint tissue composition. Full article

Background and Objectives: Periodontal disease, characterized by progressive destruction of tooth-supporting tissues, often results in substantial alveolar bone loss, necessitating regenerative interventions such as guided bone regeneration (GBR). Insulin-like growth factor 2 (IGF-2) has emerged as a promising biomolecule for periodontal regeneration because of its osteogenic and immunomodulatory properties. Materials and Methods: A comprehensive literature search was conducted across five electronic databases (Scopus, ScienceDirect, PubMed, Wiley, and EBSCO). Studies examining the use of IGF-2 in periodontal or alveolar bone regeneration, including randomized controlled trials, animal studies, and in vitro experiments, were included. Results: Three studies met the inclusion criteria. In vitro, IGF-2 was associated with enhanced osteogenic differentiation and mineralization of mesenchymal stem cells, along with upregulation of key osteogenic markers. In animal models, IGF-2 treatment was associated with increased osteogenesis, greater bone volume, and a shift in macrophage polarization toward a less inflammatory phenotype. However, heterogeneity in study designs, protocols, and outcome measures limited direct comparisons. Conclusions: In vitro, IGF-2 was associated with enhanced osteogenic differentiation and mineralization of mesenchymal stem cells, accompanied by upregulation of key osteogenic markers. In animal models, IGF-2 treatment was associated with increased osteogenesis, greater bone volume, and a shift in macrophage polarization toward a less inflammatory phenotype. Full article

Traditional hydroxyapatite materials are inherently stiff and brittle, limiting their applications. Flexible ultralong hydroxyapatite nanowires, characterized by nano-scale diameters and micrometer-scale lengths, offer a promising alternative as one-dimensional flexible building blocks for constructing high-performance biomimetic materials. Nature has evolved a variety of high-performance materials with hierarchically ordered structures assembled from nano-scale building blocks, which provide valuable insights into the design and ordered assembly of flexible nanofibers for building high-performance biomimetic materials. Currently, how to distill the structural design principles of natural materials to engineer flexible nanofibers into advanced high-performance biomimetic materials with excellent properties and multifunctions remains a frontier scientific challenge. In 2014, the authors’ research group reported for the first time the calcium oleate precursor solvothermal method for the synthesis of flexible ultralong hydroxyapatite nanowires and their applications. Since then, many soft functional materials and high-performance biomimetic materials have been designed and prepared using flexible ultralong hydroxyapatite nanowires, and their applications in various fields have been explored. These studies demonstrate the successful assembly of flexible ultralong hydroxyapatite nanowires into hierarchical biomimetic structures inspired by natural materials such as enamel, nacre, and bone, which exhibit enhanced mechanical properties, including improved strength, toughness, and flexibility, alongside multifunctional capabilities like thermal insulation and biomedical compatibility. These findings suggest that flexible ultralong hydroxyapatite nanowires provide a versatile platform for designing and constructing advanced biomimetic materials with promising applications in various fields. This review article aims to briefly review recent advances in this exciting and rapidly evolving research field. The synthetic methods, assembly strategies, properties, and applications of flexible ultralong hydroxyapatite nanowires and their derivative biomimetic materials are discussed, enlightening their structural design principles and potential applications. Finally, we propose future research directions and future perspectives in this exciting frontier research field. Full article

Fenestrations of mammalian skull bones are rare and poorly understood, particularly within the parietal bone. In bats—a group characterised by advanced sensory specialisation and echolocation—superficial modifications of the cranial vault may have functional significance, yet their occurrence and organisation remain insufficiently documented. In this study, we describe an exceptional fenestrated complex in the posterolateral parietal bone of Plecotus auritus, comprising structural elements not previously recorded within Vespertilionidae. The aim of the study was to characterise in detail the morphology, topography, and variability of the surface structure termed Fenestras Elisabeth (nova structura), with particular emphasis on its relationship with the auditory region and its potential biomechanical–acoustic significance. The material consisted of ten skulls of P. auritus, examined using micro-CT scanning, 3D reconstruction, and qualitative analysis of fenestrated structures and their topographic relationships. Within the posterolateral parietal region, we identified an extensive and repeatable fenestrated complex comprising numerous fenestrae parietales Elisabeth, paired fenestrula Elisabeth, a central depression (recessus acousticus parietalis), and a bordering fissure (fissura occipitalis mastoidea, nova structura topographica). The complex exhibited a stable spatial organisation despite individual variation in the number and shape of the openings. All fenestrations were confined to the posterolateral zone, and the contact between the fenestrae and the fissura occipitalis mastoidea represented a diagnostic feature. Our analysis suggests that the Fenestras Elisabeth complex may be associated with combined biomechanical and acoustic constraints: (1) a biomechanical role—reducing strain in the parietal lamina during movements of the extremely mobile and elongated pinnae; and (2) an acoustic role—modulating micro-vibrations transmitted to the inner-ear structures. Individual variability and lateral asymmetry of fenestration patterns indicate a high degree of adaptive plasticity in this region of the skull. This study provides the first documentation of a large, structurally organised parietal-bone fenestration complex in Plecotus auritus, expanding current knowledge of bat cranial morphology and suggesting a likely functional significance for these previously unknown bony structures. Full article

The aim of the study was to investigate the synergistic effect of conditioned medium (CM) and two types of calcium phosphate biocements on the osteogenic properties of a composite material through rat bone marrow-derived mesenchymal stem cells (MSCs). Briefly, MSCs were cultured for 7 and 17 days in extracts derived from the two biocement types. These extracts were supplemented with 5% (v/v) of concentrated CM. The CM was obtained from rat bone marrow MSC cultures after a 48 h conditioning period. The results showed that the addition of CM had a significant positive impact on the osteoblastic differentiation of MSCs, particularly in the extracts from the tetracalcium phosphate/monetite/calcium sulfate hemihydrate biocement (designated as CAS cement) compared to the other tested cement extract (designated C cement). After 17 days of culturing, a notable increase in cell viability and alkaline phosphatase (ALP) activity, as well as the upregulation of osteoblastic-related gene expression, was found. This enhancement in osteogenic activity was likely driven by the growth factors and bioactive molecules present in the CM. The study concluded that supplementing the biocement extracts with only 5% of 10X concentrated CM is sufficient to significantly influence and improve the in vitro characteristics, cell behavior, gene expression, and synthesis of cell products. It was demonstrated that, especially in the CAS supplemented with CM (CAS + CM) extract system, the improvement in osteogenic properties was due to the synergistic effect between the higher concentration of calcium ions in extracts released from the calcium sulfate hemihydrate-containing cement and the bioactive molecules supplied by the CM. Full article

Rock art in the Albarracín Cultural Park represents one of Spain’s most significant concentrations of post-Paleolithic paintings, yet comprehensive chemical characterization across multiple shelters remained lacking. This study analyzes 102 pigment samples (54 white, 31 black, 17 red) from 12 shelters using portable X-ray fluorescence spectroscopy. Centered log-ratio transformation addressed compositional data constraints, enabling multivariate analyses (PCA, LDA, MANOVA) that properly account for the constant-sum constraint inherent in geochemical data. Linear discriminant analysis achieved 92.6%–100% classification accuracy for site attribution, with barium emerging as the universal discriminating element across all pigment types (Cohen’s d = 4.91–9.19). Iron concentrations confirmed hematite/goethite use in red pigments, with inter-shelter variations suggesting different ochre sources. Black pigments revealed dual technologies: manganese oxides (pyrolusite) and carbon-based materials, with phosphorus enrichment in some samples consistent with possible bone-derived materials, though alternative phosphorus sources cannot be definitively excluded. This technological duality occurred within individual shelters, documenting greater complexity than previously recognized. White pigments combined substrate-derived materials with gypsum and aluminosilicate clay minerals (likely of the kaolinite group), occasionally incorporating phosphate-rich phases. The documented coexistence of compositionally distinct pigments within single shelters (whether from different raw material sources or varied preparation techniques) confirms the technical heterogeneity of Albarracín rock art and challenges assumptions about technological homogeneity in Levantine art production. This interplay between natural geological constraints and cultural technological choices underscores the need for complementary surface-sensitive techniques to fully resolve the technological repertoire of Levantine artists. Full article