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Hui Gao,1,* Nan Jiang,2,* Qiannan Niu,3 Shenglin Mei,4,5 Håvard Jostein Haugen,6 Qianli Ma6,7 1Department of Stomatology, the Eighth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Department of Community Dentistry, Institute of Clinical Dentistry, University of Oslo, Oslo, Norway; 3State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi Province, People’s Republic of China; 4Xingrui Dental Clinic, Xi’an, Shaanxi Province, People’s Republic of China; 5Department of Physics & Materials Science, City University of Hong Kong, Hong Kong, People’s Republic of China; 6Department of Biomaterials, Institute of Clinical Dentistry, University of Oslo, Oslo, Norway; 7Department of Immunology, School of Basic Medicine, Fourth Military Medical University, Xi’an, Shaanxi Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Håvard Jostein Haugen; Qianli Ma, Department of Biomaterials, Institute of Clinical Dentistry, University of Oslo, Oslo, 0317, Norway, Email h.j.haugen@odont.uio.no; qianlima@odont.uio.noIntroduction: Titanium (Ti) and its alloys are widely utilized in endosseous implants. However, their clinical efficacy is marred by complications arising from bacterial infections owing to their inadequate antibacterial properties. Consequently, enhancing the antibacterial attributes of implant surfaces stands as a pivotal objective in the realm of implantable materials research.Methods: In this study, we employed sequential anodization and plasma immersion ion implantation (PIII) technology to fabricate a silver-embedded sparsely titania nanotube array (SNT) on the near-β titanium alloy Ti-5Zr-3Sn-5Mo-15Nb (TLM) implants. The surface characteristics, antimicrobial properties, biocompatibility, and osteogenic activity of the silver-nanomodified SNT implant (SNT Ag) surface, alongside peri-implant inflammatory responses, were meticulously assessed through a combination of in vitro and in vivo analyses.Results: Compared with polished TLM and SNT, the silver-embedded SNT (SNT Ag) surface retained the basic shape of nanotubes and stably released Ag+ at the ppm level for a long time, which demonstrated an effective inhibition and bactericidal activity against Staphylococcus aureus (SA) while maintaining ideal cytocompatibility. Additionally, the subtle modifications in nanotubular topography induced by silver implantation endowed SNT Ag with enhanced osteogenic activity and mitigated inflammatory capsulation in soft tissue peri-implants in a rat model.Conclusion: Incorporating a silver-embedded SNT array onto the implant surface demonstrated robust antibacterial properties, impeccable cytocompatibility, exceptional osteogenic activity, and the potential to prevent inflammatory encapsulation around the implant site. The Silver-PIII modification strategy emerges as a highly promising approach for surface applications in endosseous implants and trans-gingival implant abutments.Keywords: implant surface modification, silver PIII, anti-bacterial activity, cytocompatibility, osteogenic differentiation, host inflammatory response

This study investigates osteoblastic cell spheroid cultivation methods, exploring flat-bottom, U-bottom, and rotary flask techniques with and without amorphous calcium phosphate (ACP) supplementation to replicate the 3D bone tissue microenvironment. ACP particles derived from eggshell waste exhibit enhanced osteogenic activity in 3D models. However, representative imaging of intricate 3D tissue-engineered constructs poses challenges in conventional imaging techniques due to notable scattering and absorption effects in light microscopy, and hence limited penetration depth. We investigated contrast-enhanced micro-CT as a methodological approach for comprehensive morphological 3D-analysis of the in-vitro model and compared the technique with confocal laser scanning microscopy, scanning electron microscopy and classical histology. Phosphotungstic acid and iodine-based contrast agents were employed for micro-CT imaging in laboratory and synchrotron micro-CT imaging. Results revealed spheroid shape variations and structural integrity influenced by cultivation methods and ACP particles. The study underscores the advantage of 3D spheroid models over traditional 2D cultures in mimicking bone tissue architecture and cellular interactions, emphasising the growing demand for novel imaging techniques to visualise 3D tissue-engineered models. Contrast-enhanced micro-CT emerges as a promising non-invasive imaging method for tissue-engineered constructs containing ACP particles, offering insights into sample morphology, enabling virtual histology before further analysis., (Creative Commons Attribution license.)

Background: This study presents a novel multi-technique approach that integrates micro-CT and optical photothermal infrared spectroscopy (O-PTIR) to evaluate polymerisation differences, so-called spatio-temporal polymerisation properties, between flowable and sculptable dental resin-based composites., Methods: Ten commercially available dental composites were investigated, including flowable and sculptable counterparts from the same manufacturer. Eight parameters were evaluated: short-term polymerisation characteristics (degree of conversion after 5 min, maximum polymerisation rate, time to reach maximum polymerisation rate) was measured using ATR-FTIR with real-time monitoring; changes in the degree of conversion with depth were evaluated with O-PTIR, 3D visualisation of shrinkage patterns, overall volumetric shrinkage, depth-specific shrinkage, and porosity were measured using micro-CT; surface morphology with detailed measurements of elemental composition was characterised using SEM/EDX; light transmittance was analysed with a NIST-referenced spectrometer., Results: The study found that the increase in filler weight and volume ratio reduced the degree of conversion and polymerisation shrinkage, while moderately influencing the maximum polymerisation rates. The time to reach maximum polymerisation rates and light transmittance were not dependent on the filler amount. O-PTIR assessed a depth-dependent decrease in the degree of conversion for both composite types, with flowable composites generally showing a greater decrease in the degree of conversion than sculptable composites, except for bulk-fill composites. Micro-CT scans showed significantly higher flowable shrinkage values than their sculptable counterparts, highlighting the performance differences between the two types of composites., Conclusions: The findings of this study have practical implications for the selection and use of dental composites. Flowable composites, despite their higher degrees of conversion and polymerisation rates, also exhibit higher volumetric shrinkage, which can be detrimental for clinical applications. The new measurement methods used in this study provide a comprehensive overview of the polymerisation behaviour of commercially available dental composites, offering valuable insights for material optimisation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Dental resin composites' performance is intricately linked to their polymerisation shrinkage characteristics. This study compares polymerisation shrinkage using advanced 3D micro-computed tomography (micro-CT) and traditional 2D linear assessments. It delves into the crucial role of filler content on shrinkage and the degree of conversion in dental resin composites, providing valuable insights for the field., Methods: Five experimental dental composite materials were prepared with increasing filler contents (55-75 wt%) and analysed using either 3D micro-CT for volumetric shrinkage or a custom-designed linometer for 2D linear shrinkage. The degree of conversion was assessed using Optical Photothermal Infrared (O-PTIR) and Fourier-Transform Infrared (FTIR) spectroscopy. Light transmittance through a 2-mm layer was evaluated using a NIST-calibrated spectrometer. Scanning Electron Microscopy (SEM) and Energy-Dispersive X-ray Spectroscopy (EDX) examined surface morphology and elemental distribution. Correlation between the investigated parameters was determined using Spearman correlation analyses., Results: The study found significant differences in polymerisation-related properties among different filler content categories, with volumetric shrinkage consistently demonstrating higher mean values than linear shrinkage across most groups. Volumetric shrinkage decreased with increasing curing depth, showing no direct correlation between filler content and shrinkage levels at different curing depths. The results highlighted a strong negative correlation between filler content and degree of conversion, volumetric and linear shrinkage, as well as maximum shrinkage rate. Light transmittance showed a moderate correlation with the filler content and a weak correlation with other tested parameters., Conclusions: This study underscores the importance of considering both volumetric and linear shrinkage in the design and analysis of dental composite materials. The findings advocate optimising filler content to minimise shrinkage and enhance material performance. Integrating micro-CT and O-PTIR techniques offers novel insights into dental composites' polymerisation behaviour, providing a foundation for future research to develop materials with improved clinical outcomes., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: To assess the correlation between micro-computed tomography (micro-CT) and linear morphometric measurements in terms of mandibular bone levels in a modified experimental periodontitis model in rodents to study the mechanisms of association between periodontal destruction and neuroinflammation., Methods: The proposed in vivo experimental periodontitis model involves the administration of oral rinses with Porphyromonas gingivalis and Fusobacterium nucleatum, four times per week during 4, 8 or 12 weeks, in 24 male Wistar Hannover rats (180 g, 5 weeks old). After euthanasia, hemi-mandibles were collected. One hemi-mandible was analysed using morphometry, while the other was assessed with micro-CT. Linear measurements were taken at the buccal aspect and furcation level for both techniques, and volumetric measurements were also obtained with micro-CT. Passing-Bablok regression analysis was used to compare the results of both techniques, with morphometric measurements serving as the reference. Moreover, Lin's Concordance correlation coefficient was calculated to assess the level of agreement. Periodontal clinical variables with neuroinflammatory parameters from the frontal cortex were used to evaluate the association between the resulting condition and neuroinflammation., Results: Twenty-one out of the initial 24 rats were analysed. The micro-CT linear measurements demonstrated high concordance values with the linear morphometric measurements at the buccal surfaces of the roots in molars (r = 0.714) but not at the furcation area (r = 0.052). At 12 weeks, there was a significant impact on neuroinflammation with significant decreases in iNOS levels and p-mTOR levels at 4 and 8 weeks., Conclusion: The proposed in vivo experimental periodontitis model demonstrated a high degree of correlation between morphometric and micro-CT measurements in buccal areas but not at the furcation level. Concomitantly, there was a significant temporary modulation of the neuroinflammatory response., (© 2024 The Author(s). Journal of Periodontal Research published by John Wiley & Sons Ltd.)

Aim: To develop and evaluate a novel multi-method micro-computed tomography (μCT) imaging protocol for enhanced visualization of both hard and soft tissues in murine mandibles, addressing the limitations of traditional imaging techniques in dental research., Materials and Methods: We employed a contrast-enhanced (CE) μCT imaging technique using Lugol's iodine as a contrast agent to visualize the intricate structures of murine mandibles. The protocol involved the combination of conventional μCT imaging as well as CE-μCT, including decalcification with EDTA, allowing for simultaneous assessment of hard and soft tissues. The method is compared with standard imaging modalities, and the ability to visualize detailed anatomical features is discussed., Results: The CE-μCT imaging technique provided superior visualization of murine mandibular structures, including dental pulp, periodontal ligaments and the surrounding soft tissues, along with conventional μCT imaging of alveolar bone and teeth. This method revealed detailed anatomical features with high specificity and contrast, surpassing traditional imaging approaches., Conclusion: Our findings demonstrate the potential of CE-μCT imaging with Lugol's iodine as a powerful tool for dental research. This technique offers a comprehensive view of the murine mandible, facilitating advanced studies in tissue engineering, dental pathology and the development of dental materials., (© 2024 The Author(s). Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Intervertebral disc (IVD) herniation is a prevalent spinal disorder, often necessitating surgical intervention such as microdiscectomy for symptomatic relief and nerve decompression. IVDs comprise a gel-like nucleus pulposus (NP) encased by an annulus fibrosus (AF), and their avascular nature renders them immune-privileged. Microdiscectomy exposes the residual NP to the immune system, precipitating an immune cell infiltration and attack that exacerbates IVD degeneration. While many efforts in the tissue engineering field are directed toward IVD regeneration, the inherently limited regenerative capacity due to the avascular and low-cellularity nature of the disc and the challenging mechanical environment of the spine often impedes success. This study, aiming to prevent IVD degeneration post-microdiscectomy, utilizes mucin-derived gels (Muc-gels) that form a gel at the surgical site, inspired by the natural mucin coating on living organisms to evade immune reorganization. It is shown that type I macrophages are present in severely degenerated human discs. Encapsulating IVDs within Muc-gels prevents fibrous encapsulation and macrophage infiltration in a mouse subcutaneous model. The injection of Muc-gels prevents IVD degeneration in a rat tail IVD degeneration model up to 24 weeks post-operation. Mechanistic investigations indicate that Muc-gels attenuate immune cell infiltration into NPs, offering durable protection against immune attack post-microdiscectomy., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The replication of bone physiology under laboratory conditions is a prime target behind the development of in vitro bone models. The model should be robust enough to elicit an unbiased response when stimulated experimentally, giving reproducible outcomes. In vitro bone tissue generation majorly requires the availability of cellular components, the presence of factors promoting cellular proliferation and differentiation, efficient nutrient supply, and a supporting matrix for the cells to anchor - gaining predefined topology. Calcium phosphates (CaP) are difficult to ignore while considering the above requirements of a bone model. Therefore, the current review focuses on the role of CaP in developing an in vitro bone model addressing the prerequisites of bone tissue generation. Special emphasis is given to the physico-chemical properties of CaP that promote osteogenesis, angiogenesis and provide sufficient mechanical strength for load-bearing applications. Finally, the future course of action is discussed to ensure efficient utilization of CaP in the in vitro bone model development field., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Xenografts are commonly used for bone regeneration in dental and orthopaedic domains to repair bone voids and other defects. The first-generation xenografts were made through sintering, which deproteinizes them and alters their crystallinity, while later xenografts are produced using cold-temperature chemical treatments to maintain the structural collagen phase. However, the impact of collagen and the crystalline phase on physicochemical properties have not been elucidated. We hypothesized that understanding these factors could explain why the latter provides improved bone regeneration clinically. In this study, we compared two types of xenografts, one prepared through a low-temperature chemical process (Treated) and another subsequently sintered at 1100°C (Sintered) using advanced microscopy, spectroscopy, X-ray analysis and compressive testing. Our investigation showed that the Treated bone graft was free of residual blood, lipids or cell debris, mitigating the risk of pathogen transmission. Meanwhile, the sintering process removed collagen and the carbonate phase of the Sintered graft, leaving only calcium phosphate and increased mineral crystallinity. Microcomputed tomography revealed that the Treated graft exhibited an increased high porosity (81%) and pore size compared to untreated bone, whereas the Sintered graft exhibited shrinkage, which reduced the porosity (72%), pore size and strut size. Additionally, scanning electron microscopy displayed crack formation around the pores of the Sintered graft. The Treated graft displayed median mechanical properties comparable to native cancellous bone and clinically available solutions, with an apparent modulus of 166 MPa, yield stress of 5.5 MPa and yield strain of 4.9%. In contrast, the Sintered graft exhibited a lower median apparent modulus of 57 MPa. It failed in a brittle manner at a median stress of 1.7 MPa and strain level of 2.9%, demonstrating the structural importance of the collagen phase. This indicates why bone grafts prepared through cold-temperature processes are clinically favourable., (© The Author(s) 2024. Published by Oxford University Press.)

Introduction: The effectiveness of multiple-choice questions (MCQs) in dental education is pivotal to student performance and knowledge advancement. However, their optimal implementation requires exploration to enhance the benefits., Materials and Methods: An educational tool incorporating MCQs was administered from the 5th to the 10th semester in a dental curriculum. The students filled out a questionnaire after the MCQ, which was linked to the learning management system. Four cohorts of four semesters generated 2300 data points analysed by Spearmen correlation and mixed model regression analysis., Results: Demonstrated a significant correlation between early exam preparation and improved student performance. Independent study hours and lecture attendance emerged as significant predictors, accounting for approximately 10.27% of the variance in student performance on MCQs. While the number of MCQs taken showed an inverse relationship with study hours, the perceived clarity of these questions positively correlated with academic achievement., Conclusion: MCQs have proven effective in enhancing student learning and knowledge within the discipline. Our analysis underscores the important role of independent study and consistent lecture attendance in positively influencing MCQ scores. The study provides valuable insights into using MCQs as a practical tool for dental student learning. Moreover, the clarity of assessment tools, such as MCQs, remains pivotal in influencing student outcomes. This study underscores the multifaceted nature of learning experiences in dental education and the importance of bridging the gap between student expectations and actual performance., (© 2024 The Authors. European Journal of Dental Education published by John Wiley & Sons Ltd.)

Objectives: This study aims to assess the risk of peri-implantitis (PI) onset among different implant systems and evaluate the severity of the disease from a population of patients treated in a university clinic. Furthermore, this study intends to thoroughly examine the surface properties of the implant systems that have been identified and investigated., Material and Methods: Data from a total of six hundred and 14 patients were extracted from the Institute of Clinical Dentistry, Dental Faculty, University of Oslo. Subject- and implant-based variables were collected, including the type of implant, date of implant installation, medical records, recall appointments up to 2022, periodontal measurements, information on diabetes, smoking status, sex, and age. The outcome of interest was the diagnosis of PI, defined as the occurrence of bleeding on probing (BoP), peri-implant probing depth (PD) ≥ 5 mm, and bone loss (BL). Data were analyzed using multivariate linear and logistic regression. Scanning electron microscopy, light laser profilometer, and X-ray photoelectron spectroscopy were utilized for surface and chemical analyses., Results: Among the patients evaluated, 6.8% were diagnosed with PI. A comparison was made between two different implant systems: Dentsply Sirona, OsseospeedTM and Straumann SLActive, with mean follow-up times of 3.84 years (SE: 0.15) and 3.34 years (SE: 0.15), respectively. The surfaces have different topographies and surface chemistry. However, no significant association was found between PI and implant surface/system, including no difference in the onset or severity of the disease. Nonetheless, plaque control was associated with an increased risk of developing PI, along with the gender of the patient. Furthermore, patients suffering from PI exhibited increased BL in the anterior region., Conclusion: No differences were observed among the evaluated implant systems, although the surfaces have different topography and chemistry. Factors that affected the risk of developing PI were plaque index and male gender. The severity of BL in patients with PI was more pronounced in the anterior region. Consequently, our findings show that success in implantology is less contingent on selecting implant systems and more on a better understanding of patient-specific risk factors, as well as on implementing biomaterials that can more effectively debride dental implants.

Objectives: Composites with copper-doped mesoporous bioactive nanospheres (Cu-MBGN) were developed to prevent secondary caries by imparting antimicrobial and ion-releasing/remineralizing properties., Methods: Seven experimental composites containing 1, 5 or 10 wt% Cu-MBGN, the corresponding inert controls (silica) and bioactive controls (bioactive glass 45S5) were prepared. The temperature rise during light curing, cross-linking density by ethanol softening test, monomer elution and their potential adverse effects on the early development of zebrafish Danio rerio was investigated., Results: Materials combining Cu-MBGN and silica showed the highest resistance to ethanol softening, as did the bioactive controls. Cu-MBGN composites showed significant temperature rise and reached maximum temperature in the shortest time. Bisphenol A was not detected, while bis-GMA was found only in the control materials and TEGDMA in the eluates of all materials. There was no increase in zebrafish mortality and abnormality rates during exposure to the eluates of any of the materials., Conclusions: The composite with 5 wt% Cu-MBGN combined with nanosilica fillers showed the lowest ethanol softening, indicating the polymer's highest durability and cross-linking density. Despite the TEGDMA released from all tested materials, no embryotoxic effect was observed., Competing Interests: Declaration of Competing Interest The authors of the manuscript „The influence of copper-doped mesoporous bioactive nanospheres on the temperature rise during polymerization, polymer cross-linking density, monomer release and embryotoxicity of dental composites" submitted to Dental Materials declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Obtaining rapid mineralisation is a challenge in current bone graft materials, which has been attributed to the difficulty of guiding the biological processes towards osteogenesis. Amelogenin, a key protein in enamel formation, inspired the design of two intrinsically disordered peptides (P2 and P6) that enhance in vivo bone formation, but the process is not fully understood. In this study, we have elucidated the mechanism by which these peptides induce improved mineralisation. Our molecular dynamics analysis demonstrated that in an aqueous environment, P2 and P6 fold to interact with the surrounding Ca 2+ , PO 4 3- and OH - ions, which can lead to apatite nucleation. Although P2 has a less stable backbone, it folds to a stable structure that allows for the nucleation of larger calcium phosphate aggregates than P6. These results were validated experimentally in a concentrated simulated body fluid solution, where the peptide solutions accelerated the mineralisation process compared to the control and yielded mineral structures mimicking the amorphous calcium phosphate crystals that can be found in lamella bone. A pH drop for the peptide groups suggests depletion of calcium and phosphate, a prerequisite for intrinsic osteoinduction, while S/TEM and SEM suggested that the peptide regulated the mineral nucleation into lamella flakes. Evidently, the peptides accelerate and guide mineral formation, elucidating the mechanism for how these peptides can improve the efficacy of P2 or P6 containing devices for bone regeneration. The work also demonstrates how experimental mineralisation study coupled with molecular dynamics is a valid method for understanding and predicting in vivo performance prior to animal trials., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare no financial and personal relationships with other people or organisations that could inappropriately influence bias to this work. IPR rights of the consensus peptides (US Patent US8367602B2 and connected titles) belong to Industrie Biomediche Insubri SA (Switzerland), where Giuseppe Perale is a founding shareholder and the executive vice president. The patent related to the consensus peptides was invented by Ståle Petter Lyngstadaas but has since been sold to Industrie Biomediche Insubri SA. NuPep AS, owned solely by Øystein Øvrebø, has a licencing right to the consensus peptides IPR above., (Published by Elsevier B.V.)

Periodontitis is a dysbiosis-driven inflammatory disease affecting the tooth-supporting tissues, characterized by their progressive resorption, which can ultimately lead to tooth loss. A step-wise therapeutic approach is employed for periodontitis. After an initial behavioral and non-surgical phase, intra-bony or furcation defects may be amenable to regenerative procedures. This review discusses the regenerative technologies employed for periodontal regeneration, highlighting the current limitations and future research areas. The search, performed on the MEDLINE database, has identified the available biomaterials, including biologicals (autologous platelet concentrates, hydrogels), bone grafts (pure or putty), and membranes. Biologicals and bone grafts have been critically analyzed in terms of composition, mechanism of action, and clinical applications. Although a certain degree of periodontal regeneration is predictable in intra-bony and class II furcation defects, complete defect closure is hardly achieved. Moreover, treating class III furcation defects remains challenging. The key properties required for functional regeneration are discussed, and none of the commercially available biomaterials possess all the ideal characteristics. Therefore, research is needed to promote the advancement of more effective and targeted regenerative therapies for periodontitis. Lastly, improving the design and reporting of clinical studies is suggested by strictly adhering to the Consolidated Standards of Reporting Trials (CONSORT) 2010 statement., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

This study investigates the effect of scaffold architecture on bone regeneration, focusing on 3D-printed polylactic acid-bioceramic calcium phosphate (PLA-bioCaP) composite scaffolds in rabbit femoral condyle critical defects. We explored two distinct scaffold designs to assess their influence on bone healing and scaffold performance. Structures with alternate (0°/90°) and helical (0°/45°/90°/135°/180°) laydown patterns were manufactured with a 3D printer using a fused deposition modeling technique. The scaffolds were meticulously characterized for pore size, strut thickness, porosity, pore accessibility, and mechanical properties. The in vivo efficacy of these scaffolds was evaluated using a femoral condyle critical defect model in eight skeletally mature New Zealand White rabbits. Then, the results were analyzed micro-tomographically, histologically, and histomorphometrically. Our findings indicate that both scaffold architectures are biocompatible and support bone formation. The helical scaffolds, characterized by larger pore sizes and higher porosity, demonstrated significantly greater bone regeneration than the alternate structures. However, their lower mechanical strength presented limitations for use in load-bearing sites.

The surge in 'Big data' has significantly influenced biomaterials research and development, with vast data volumes emerging from clinical trials, scientific literature, electronic health records, and other sources. Biocompatibility is essential in developing safe medical devices and biomaterials to perform as intended without provoking adverse reactions. Therefore, establishing an artificial intelligence (AI)-driven biocompatibility definition has become decisive for automating data extraction and profiling safety effectiveness. This definition should both reflect the attributes related to biocompatibility and be compatible with computational data-mining methods. Here, we discuss the need for a comprehensive and contemporary definition of biocompatibility and the challenges in developing one. We also identify the key elements that comprise biocompatibility, and propose an integrated biocompatibility definition that enables data-mining approaches., Competing Interests: Declaration of Interests The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Eradicating biofouling from implant surfaces is essential in treating peri-implant infections, as it directly addresses the microbial source for infection and inflammation around dental implants. This controlled laboratory study examines the effectiveness of the four commercially available debridement solutions '(EDTA (Prefgel ® ), NaOCl (Perisolv ® ), H 2 O 2 (Sigma-Aldrich) and Chlorhexidine (GUM ® Paroex ® ))' in removing the acquired pellicle, preventing pellicle re-formation and removing of a multi-species oral biofilm growing on a titanium implant surface, and compare the results with the effect of a novel formulation of a peroxide-activated 'Poloxamer gel (Nubone ® Clean)'. Evaluation of pellicle removal and re-formation was conducted using scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy to assess the surface morphology, elemental composition and chemical surface composition. Hydrophilicity was assessed through contact angle measurements. The multi-species biofilm model included Streptococcus oralis , Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans , reflecting the natural oral microbiome's complexity. Biofilm biomass was quantified using safranin staining, biofilm viability was evaluated using confocal laser scanning microscopy, and SEM was used for morphological analyses of the biofilm. Results indicated that while no single agent completely eradicated the biofilm, the 'Poloxamer gel' activated with 'H 2 O 2 ' exhibited promising results. It minimized re-contamination of the pellicle by significantly lowering the contact angle, indicating enhanced hydrophilicity. This combination also showed a notable reduction in carbon contaminants, suggesting the effective removal of organic residues from the titanium surface, in addition to effectively reducing viable bacterial counts. In conclusion, the 'Poloxamer gel + H 2 O 2 ' combination emerged as a promising chemical decontamination strategy for peri-implant diseases. It underlines the importance of tailoring treatment methods to the unique microbial challenges in peri-implant diseases and the necessity of combining chemical decontaminating strategies with established mechanical cleaning procedures for optimal management of peri-implant diseases., (© The Author(s) 2024. Published by Oxford University Press.)

Background: The cornea, a vital component of the human eye, plays a crucial role in maintaining visual clarity. Understanding its ultrastructural organization and cell distribution is fundamental for elucidating corneal physiology and pathology. This study comprehensively examines the microarchitecture of the hydrated human cornea using contrast-enhanced micro-computed tomography (micro-CT)., Method: Fresh human corneal specimens were carefully prepared and hydrated to mimic their in vivo state. Contrast enhancement with Lugol's iodine-enabled high-resolution Micro-CT imaging. The cells' three-dimensional (3D) distribution within the cornea was reconstructed and analyzed., Results: The micro-CT imaging revealed exquisite details of the corneal ultrastructure, including the spatial arrangement of cells throughout its depth. This novel approach allowed for the visualization of cells' density and distribution in different corneal layers. Notably, our findings highlighted variations in cell distribution between non-hydrated and hydrated corneas., Conclusions: This study demonstrates the potential of contrast-enhanced micro-CT as a valuable tool for non-destructive, 3D visualization and quantitative analysis of cell distribution in hydrated human corneas. These insights contribute to a better understanding of corneal physiology and may have implications for research in corneal diseases and tissue engineering., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objectives: This study aimed to determine the degree of similarity and symmetry in the anatomy of contralateral mandibular incisors. Three-dimensional (3D) models of extracted teeth were obtained from microtomography (micro-CT) scans. Qualitative and quantitative assessments of the morphology and comparison of contralateral pairs were made. The null hypothesis was that contralateral mandibular incisors could not be considered identical in simple morphometric measurements., Methods: Sixty pairs of mandibular incisors were extracted from 30 patients and scanned with micro-CT. Virtual models of the cemento-enamel junction to the root apex were rendered. Parameters such as length, canal width, dentinal thicknesses, tortuosity, centerline length, accessory canals, root canal configurations, and root canal orifice cross-sections were used to compare the teeth. Width and thickness comparisons between paired teeth in the same individual were made by paired t-test (Wilcoxon signed-rank test for variables not normally distributed). An online randomization tool generated randomized pairs (independent of the individual/patient). Subsequently, an unpaired t-test (or Mann-Whitney U test for non-normally distributed parameters) and a correlation analysis were conducted. Canal configurations were classified according to preexisting classification schemes. The number and location of accessory canals and apical foramina were registered and compared., Results: Utilizing advanced imaging techniques and quantitative analyses, our study establishes that contralateral mandibular incisors exhibit a remarkable degree of symmetry in multiple morphological parameters, including length, canal width, and dentinal thicknesses. The apical third showed a high degree of inter-variability for the contralateral pairs. The rigorous statistical analysis of the normalized parameters by Z-score showed no statistically significant differences between the contralateral mandibular incisors. Comparisons between central and lateral teeth revealed differences in root length but no significant disparity in the distribution of accessory canals. Central teeth, on average, were longer, while accessory canals were distributed relatively evenly between central and lateral teeth., Conclusions: The findings of this study further establish the significant similarities between contralateral mandibular incisors, reinforcing their suitability as a reliable substrate for root canal comparison studies., Clinical Relevance: The absence of statistically significant differences between contralateral pairs in normalized parameters underscores their potential as a reliable reference point for root canal comparison studies in clinical dentistry. Furthermore, our findings emphasize the importance of individualized treatment planning, considering the natural symmetry in mandibular incisors to enhance clinical decision-making. This research contributes valuable insights to the field of endodontics, offering a standardized approach to sample selection and enriching the understanding of dental anatomy., (© 2023. The Author(s).)

Intra-portal islet transplantation is currently the only clinically approved beta cell replacement therapy, but its outcome is hindered by limited cell survival due to a multifactorial reaction against the allogeneic tissue in liver. Adipose-derived stromal cells (ASCs) can potentially improve the islet micro-environment by their immunomodulatory action. The challenge is to combine both islets and ASCs in a relatively easy and consistent long-term manner in a deliverable scaffold. Manufacturing the 3D bioprinted double-layered scaffolds with primary islets and ASCs using a mix of alginate/nanofibrillated cellulose (NFC) bioink is reported. The diffusion properties of the bioink and the supportive effect of human ASCs on islet viability, glucose sensing, insulin secretion, and reducing the secretion of pro-inflammatory cytokines are demonstrated. Diabetic mice transplanted with islet-ASC scaffolds reach normoglycemia seven days post-transplantation with no significant difference between this group and the group received islets under the kidney capsules. In addition, animals transplanted with islet-ASC scaffolds stay normoglycemic and show elevated levels of C-peptide compared to mice transplanted with islet-only scaffolds. The data present a functional 3D bioprinted scaffold for islets and ASCs transplanted to the extrahepatic site and suggest a possible role of ASCs on improving the islet micro-environment., (© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Micro-computed tomography (micro-CT) provides valuable data for studying soft tissue, though it is often affected by sample movement during scans and low contrast in X-ray absorption. This can result in lower image quality and geometric inaccuracies, collectively known as 'artefacts'. To mitigate these issues, samples can be embedded in hydrogels and enriched with heavy metals for contrast enhancement. However, the long-term durability of these enhancements remains largely unexplored. In this study, we examine the effects of two contrast enhancement agents - iodine and phosphotungstic acid (PTA) - and two hydrogels - agarose and Poloxamer 407 - over a 14-day period. We used Drosophila melanogaster as a test model for our investigation. Our findings reveal that PTA and agarose are highly durable, while iodine and poloxamer hydrogel exhibits higher leakage rates. These observations lay the foundation for estimating contrast stabilities in contrast-enhanced micro-CT with hydrogel embedding and serve to inform future research in this field., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

3D-printed composite scaffolds have emerged as an alternative to deal with existing limitations when facing bone reconstruction. The aim of the study was to systematically review the feasibility of using PLA/bioceramic composite scaffolds manufactured by 3D-printing technologies as bone grafting materials in preclinical in vivo studies. Electronic databases were searched using specific search terms, and thirteen manuscripts were selected after screening. The synthesis of the scaffolds was carried out using mainly extrusion-based techniques. Likewise, hydroxyapatite was the most used bioceramic for synthesizing composites with a PLA matrix. Among the selected studies, seven were conducted in rats and six in rabbits, but the high variability that exists regarding the experimental process made it difficult to compare them. Regarding the results, PLA/Bioceramic composite scaffolds have shown to be biocompatible and mechanically resistant. Preclinical studies elucidated the ability of the scaffolds to be used as bone grafts, allowing bone growing without adverse reactions. In conclusion, PLA/Bioceramics scaffolds have been demonstrated to be a promising alternative for treating bone defects. Nevertheless, more care should be taken when designing and performing in vivo trials, since the lack of standardization of the processes, which prevents the comparison of the results and reduces the quality of the information. STATEMENT OF SIGNIFICANCE: 3D-printed polylactic acid/bioceramic composite scaffolds have emerged as an alternative to deal with existing limitations when facing bone reconstruction. Since preclinical in vivo studies with animal models represent a mandatory step for clinical translation, the present manuscript analyzed and discussed not only those aspects related to the selection of the bioceramic material, the synthesis of the implants and their characterization. But provides a new approach to understand how the design and perform of clinical trials, as well as the selection of the analysis methods, may affect the obtained results, by covering authors' knowledgebase from veterinary medicine to biomaterial science. Thus, this study aims to systematically review the feasibility of using polylactic acid/bioceramic scaffolds as grafting materials in preclinical trials., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing of interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The role of poroelasticity on the functional performance of articular cartilage has been established in the scientific literature since the 1960s. Despite the extensive knowledge on this topic there remain few attempts to design for poroelasticity and to our knowledge no demonstration of an engineered poroelastic material that approaches the physiological performance. In this paper, we report on the development of an engineered material that begins to approach physiological poroelasticity. We quantify poroelasticity using the fluid load fraction, apply mixture theory to model the material system, and determine cytocompatibility using primary human mesenchymal stem cells. The design approach is based on a fiber reinforced hydrated network and uses routine fabrication methods (electrohydrodynamic deposition) and materials (poly[ɛ-caprolactone] and gelatin) to develop the engineered poroelastic material. This composite material achieved a mean peak fluid load fraction of 68%, displayed consistency with mixture theory, and demonstrated cytocompatibility. This work creates a foundation for designing poroelastic cartilage implants and developing scaffold systems to study chondrocyte mechanobiology and tissue engineering. STATEMENT OF SIGNIFICANCE: Poroelasticity drives the functional mechanics of articular cartilage (load bearing and lubrication). In this work we develop the design rationale and approach to produce a poroelastic material, known as a fiber reinforced hydrated network (FiHy™), that begins to approach the native performance of articular cartilage. This is the first engineered material system capable of exceeding isotropic linear poroelastic theory. The framework developed here enables fundamental studies of poroelasticity and the development of translational materials for cartilage repair., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aim: To evaluate the hard and soft tissues healing around teeth prepared with the biologically oriented preparation technique (BOPT) versus the chamfer technique versus non-prepared teeth., Materials and Methods: Thirty-two teeth in eight beagle dogs were randomly prepared with the BOPT (test = 16) or chamfer (control = 16) techniques and covered with polymethylmethacrylate crowns as provisional restorations. Sixteen negative controls (non-prepared teeth) were also used for comparison. Histological description and histomorphometrical measurements of the periodontal tissues were collected at 4 and 12 weeks in 7 out of 8 dogs, including the soft tissue height and thickness, and the horizontal and vertical bone dimensions., Results: When compared with negative controls, test and control preparation techniques exhibited a more apical location of the free gingival margin with respect to the cement-enamel junction (∆ = 1.1 mm for both groups at 4 weeks (p < .05), 0.99 mm for the test group (p = .043) and 0.20 mm for control group (p = 1.000) at 12 weeks). There were no significant differences between test and control groups with respect to vertical and horizontal histometric measurements., Conclusions: The BOPT and chamfer tooth preparation protocols induced similar qualitative and quantitative changes in the healing of the supra-crestal soft tissue complex, when compared with non-prepared teeth. Despite the limited amount of power, it appeared that differences between the tested preparation techniques were not statistically significant., (© 2023 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Amorphous iron-calcium phosphate (Fe-ACP) plays a vital role in the mechanical properties of teeth of some rodents, which are very hard, but its formation process and synthetic route remain unknown. Here, the synthesis and characterization of an iron-bearing amorphous calcium phosphate in the presence of ammonium iron citrate (AIC) are reported. The iron is distributed homogeneously on the nanometer scale in the resulting particles. The prepared Fe-ACP particles can be highly stable in aqueous media, including water, simulated body fluid, and acetate buffer solution (pH 4). In vitro study demonstrates that these particles have good biocompatibility and osteogenic properties. Subsequently, Spark Plasma Sintering (SPS) is utilized to consolidate the initial Fe-ACP powders. The results show that the hardness of the ceramics increases with the increase of iron content, but an excess of iron leads to a rapid decline in hardness. Calcium iron phosphate ceramics with a hardness of 4 GPa can be achieved, which is higher than that of human enamel. Furthermore, the ceramics composed of iron-calcium phosphates show enhanced acid resistance. This study provides a novel route to prepare Fe-ACP, and presents the potential role of Fe-ACP in biomineralization and as starting material to fabricate acid-resistant high-performance bioceramics., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Surface chemistry evaluation is crucial in assessing the efficacy of chemical decontamination products for titanium implants. This study aimed to investigate the effectiveness of chemical decontamination solutions in cleaning a contaminated dental implant surface and to evaluate the potential of combining Pluronic gel with hydrogen peroxide (NuBone ® Clean) by evaluating pellicle disruption and re-formation on implant surfaces. In addition, ensuring safety with in vitro and human testing protocols. X-ray Photoelectron Spectroscopy (XPS) was utilised for surface analysis. All the tested gels had some effect on the surface cleanness except for PrefGel ® . Among the tested chemical decontamination candidates, NuBone ® Clean demonstrated effectiveness in providing a cleaner titanium surface. Furthermore, none of the tested chemical agents exhibited cytotoxic effects, and the safety assessment showed no adverse events. The results of this study highlight the significance of conducting comprehensive evaluations, encompassing safety and efficacy, before introducing new chemical agents for dental treatments. The findings suggest that NuBone ® Clean shows potential as a chemical decontamination solution for implant surfaces. However, further investigation through randomised clinical trials is necessary. By adhering to rigorous testing protocols, the development of safe and efficient chemical decontamination strategies can be advanced, benefiting patients and promoting progress in implant dentistry.

In vitro models of primary human osteocytes embedded in natural mineralized matrix without artificial scaffolds are lacking. We have established cell culture conditions that favored the natural 3D orientation of the bone cells and stimulated the cascade of signaling needed for primary human osteoblasts to differentiate into osteocytes with the characteristically phenotypical dendritic network between cells. Primary human osteoblasts cultured in a 3D rotating bioreactor and incubated with a combination of vitamins A, C, and D for up to 21 days produced osteospheres resembling native bone. Osteocyte-like cells were identified as entrapped, stellate-shaped cells interconnected through canaliculi embedded in a structured, mineralized, collagen matrix. These cells expressed late osteoblast and osteocyte markers such as osteocalcin (OCN), podoplanin (E11), dentin matrix acidic phosphoprotein 1 (DMP1), and sclerostin (SOST). Organized collagen fibrils, observed associated with the cell hydroxyapatite (HAp) crystals, were found throughout the spheroid and in between the collagen fibrils. In addition to osteocyte-like cells, the spheroids consisted of osteoblasts at various differentiation stages surrounded by a rim of cells resembling lining cells. This resemblance to native bone indicates a model system with potential for studying osteocyte-like cell differentiation, cross-talk between bone cells, and the mineralization process in a bonelike structure in vitro without artificial scaffolds. In addition, natural extracellular matrix may allow for the study of tissue-specific biochemical, biophysical, and mechanical properties. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., (© 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

In 1892, J.L. Wolff proposed that bone could respond to mechanical and biophysical stimuli as a dynamic organ. This theory presents a unique opportunity for investigations on bone and its potential to aid in tissue repair. Routine activities such as exercise or machinery application can exert mechanical loads on bone. Previous research has demonstrated that mechanical loading can affect the differentiation and development of mesenchymal tissue. However, the extent to which mechanical stimulation can help repair or generate bone tissue and the related mechanisms remain unclear. Four key cell types in bone tissue, including osteoblasts, osteoclasts, bone lining cells, and osteocytes, play critical roles in responding to mechanical stimuli, while other cell lineages such as myocytes, platelets, fibroblasts, endothelial cells, and chondrocytes also exhibit mechanosensitivity. Mechanical loading can regulate the biological functions of bone tissue through the mechanosensor of bone cells intraosseously, making it a potential target for fracture healing and bone regeneration. This review aims to clarify these issues and explain bone remodeling, structure dynamics, and mechano-transduction processes in response to mechanical loading. Loading of different magnitudes, frequencies, and types, such as dynamic versus static loads, are analyzed to determine the effects of mechanical stimulation on bone tissue structure and cellular function. Finally, the importance of vascularization in nutrient supply for bone healing and regeneration was further discussed., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

The design principle of osteogenic bone grafts has shifted from immunological inertness to limiting foreign body response to combined osteoimmunomodulatory activity to promote high-quality endogenous bone regeneration. Recently developed immunomodulatory mucin hydrogels have been shown to elicit very low complement activation and suppress macrophage release and activation after implantation in vivo . However, their immunoregulatory activity has not yet been studied in the context of tissue repair. Herein, we synthesized mucin-monetite composite materials and investigated their early osteoimmunomodulation using a critical-size rat bone defect model. We demonstrated that the composites can polarize macrophages towards the M2 phenotype at weeks 1 and 2. The early osteoimmunomodulation enhanced early osteogenesis and angiogenesis and ultimately promoted fracture healing and engraftment (revascularization of the host vasculature) at weeks 6 and 12. Overall, we demonstrated the applicability of mucin-based immunomodulatory biomaterials to enhance tissue repair in tissue engineering and regenerative medicine., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could appear to influence the work reported in this paper., (© 2023 The Authors.)

Objectives: To evaluate osteogenic markers and alveolar ridge profile changes in guided bone regeneration (GBR) of chronic noncontained bone defects using a nonresorbable TiO 2 block., Materials and Methods: Three buccal bone defects were created in each hemimandible of eight beagle dogs and allowed to heal for 8 weeks before GBR. Treatment was assigned by block randomization: TiO 2 block: TiO 2 -scaffold and a collagen membrane, DBBM particulates: Deproteinized bovine bone mineral (DBBM) and a collagen membrane, Empty control: Only collagen membrane. Bone regeneration was assessed on two different healing timepoints: early (4 weeks) and late healing (12 weeks) using several immunohistochemistry markers including alpha-smooth muscle actin (α-SMA), osteopontin, osteocalcin, tartrate-resistant acid phosphatase, and collagen type I. Histomorphometry was performed on Movat Pentachrome-stained and Von Kossa/Van Gieson-stained sections. Stereolithographic (STL) models were used to compare alveolar profile changes., Results: The percentage of α-SMA and osteopontin increased in TiO 2 group after 12 weeks of healing at the bone-scaffold interface, while collagen type I increased in the empty control group. In the defect area, α-SMA decreased in the empty control group, while collagen type I increased in the DBBM group. All groups maintained alveolar profile from 4 to 12 weeks, but TiO 2 group demonstrated the widest soft tissue contour profile., Conclusions: The present findings suggested contact osteogenesis when GBR is performed with a TiO 2 block or DBBM particulates. The increase in osteopontin indicated a potential for bone formation beyond 12 weeks. The alveolar profile data indicated a sustained lateral increase in lateral bone augmentation using a TiO 2 block and a collagen membrane, as compared with DBBM and a collagen membrane or a collagen membrane alone., (© 2022 The Authors. Clinical Implant Dentistry and Related Research published by Wiley Periodicals LLC.)

Background: Microgravity directly disturbs the reorganization of the cytoskeleton, exerting profound effects on the physiological process of macrophages. Although it has been established that macrophage M1/M2 polarization could be manipulated by the surface nanostructure of biomaterial in our previous study under normal gravity, how will inflammatory monocytes (iMos)-derived macrophages respond to diverse nanostructured Ti surfaces under normal gravity or microgravity remains unrevealed., Results: In this study, Cytochalasin D, a cytoskeleton relaxant, was employed to establish the simulated microgravity (SMG) environment. Our results showed that human iMos polarized into M2c macrophages on NT5 surface but M1 type on NT20 surface with divergent inflammatory phenotypes according to the profile of macrophage polarization featured molecules under normal gravity. However, such manipulative effects of NTs surfaces on iMos-derived macrophages were strikingly weakened by SMG, characterized by the altered macrophage morphology, changed cytokine secretion profile, and decreased cell polarization capacity., Conclusions: To our knowledge, this is the first metallic implantable material study focusing on the functions of specific monocyte subsets and its crucial role of the cytoskeleton in materials-mediated host immune response, which enriches our mechanism knowledge about the crosstalk between immunocytes and biomaterials. The results obtained in the present study may also provide potential targets and strategies for biomaterial development and clinical treatment via precise immune-regulation under normal gravity and microgravity., (© 2023. The Author(s).)

Introduction: The conventional treatment for irreversibly inflamed or necrotic teeth is root canal treatment or apexification. Regenerative endodontics aims to regenerate the damaged "pulp-like" tissue, which can preserve the teeth' vitality and sensitivity while avoiding necrosis. The main clinical benefit is root maturation. The "pulp-like" tissue does not refer to regenerated pulp tissue with an odontoblastic layer or the formation of pulp-dentin complexes. The cell homing technique is built on endogenous stem cells and their capacity to regenerate tissue. Cell homing refers to endogenous cells' migration or infiltration into the cite when stimulated by physiochemical or biological stimuli or by passive flow with a blood clot from the apical tissue. Its Regenerative Endodontic Procedures success criteria are defined by the American Association of Endodontists. The purpose of this article is to provide an overview of vital pulp tissue and various strategies to promote regeneration of damaged pulp tissue. The cell homing technique will be reviewed through clinical trials., Methods: We performed a comprehensive literature review on a total of nine clinical trials of regenerative endodontics using the cell-homing technique based on three databases and duplicate manuscripts were removed., Results: Regenerative endodontics using the cell-homing technique shows promising results that can be translated into clinical practice. However, a favorable result was observed in immature teeth, and the results are contradictory in mature teeth., Conclusion: Regeneration therapy is an attractive new alternative to conventional endodontic treatments. Preservation of vitality and continuation of root development in damaged teeth would be a clear advantage., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Experimental dental resin composites containing copper-doped mesoporous bioactive glass nanospheres (Cu-MBGN) were developed to impart anti-bacterial properties. Increasing amounts of Cu-MBGN (0, 1, 5 and 10 wt%) were added to the BisGMA/TEGDMA resin matrix containing micro- and nano-fillers of inert glass, keeping the resin/filler ratio constant. Surface micromorphology and elemental analysis were performed to evaluate the homogeneous distribution of filler particles. The study investigated the effects of Cu-MBGN on the degree of conversion, polymerization shrinkage, porosity, ion release and anti-bacterial activity on S. mutans and A. naeslundii . Experimental materials containing Cu-MBGN showed a dose-dependent Cu release with an initial burst and a further increase after 28 days. The composite containing 10% Cu-MBGN had the best anti-bacterial effect on S. mutans , as evidenced by the lowest adherence of free-floating bacteria and biofilm formation. In contrast, the 45S5-containing materials had the highest S. mutans adherence. Ca release was highest in the bioactive control containing 15% 45S5, which correlated with the highest number of open porosities on the surface. Polymerization shrinkage was similar for all tested materials, ranging from 3.8 to 4.2%, while the degree of conversion was lower for Cu-MBGN materials. Cu-MBGN composites showed better anti-bacterial properties than composites with 45S5 BG.

Background: Superior mesenteric artery plexus (SMAP) injury is reported to cause postoperative intractable diarrhea after pancreatic/colonic surgery with extended lymphadenectomy. This study aims to describe the SMAP microanatomy and extent of injury after right colectomy with extended D3 mesenterectomy for cancer., Methods: Three groups (I) anatomical dissection, (II) postmortem histology, and (III) surgical specimen histology were included. Nerve count and area were compared between groups II and III and paravascular sheath thickness between groups I and II. 3D models were generated through 3D histology, nanoCT scanning, and finally through 3D printing., Results: A total of 21 specimens were included as follows: Group (I): 5 (3 females, 80-93 years), the SMAP is a complex mesh surrounding the superior mesenteric artery (SMA), branching out, following peripheral arteries and intertwining between them, (II): 7 (5 females, 71-86 years), nerve count: 53 ± 12.42 (38-68), and area: 1.84 ± 0.50 mm 2 (1.16-2.29), and (III): 9 (5 females, 55-69 years), nerve count: 31.6 ± 6.74 (range 23-43), and area: 0.889 ± 0.45 mm 2 (range 0.479-1.668). SMAP transection injury is 59% of nerve count and 48% of nerve area at middle colic artery origin level. The median values of paravascular sheath thickness decreased caudally from 2.05 to 1.04 mm (anatomical dissection) and from 2.65 to 1.17 mm (postmortem histology). 3D histology models present nerve fibers exclusively within the paravascular sheath, and lymph nodes were observed only outside. NanoCT-derived models reveal oblique nerve fiber trajectories with inclinations between 35° and 55°. Two 3D-printed models of the SMAP were also achieved in a 1:2 scale., Conclusion: SMAP surrounds the SMA and branches within the paravascular sheath, while bowel lymph nodes and vessels lie outside. Extent of SMAP injury on histological slides (transection only) was 48% nerve area and 59% nerve count. The 35°-55° inclination range of SMAP nerves possibly imply an even larger injury when plexus excision is performed (lymphadenectomy). Reasons for later improvement of bowel function in these patients can lie in the interarterial nerve fibers between SMA branches., (© 2022. The Author(s).)

We embedded copper-doped mesoporous bioactive glass nanospheres (Cu-MBGN) with antibacterial and ion-releasing properties into experimental dental composites and investigated the effect of Cu-MBGN on the polymerisation properties. We prepared seven composites with a BisGMA/TEGDMA (60/40) matrix and 65 wt.% total filler content, added Cu-MBGN or a combination of Cu-MBGN and silanised silica to the silanised barium glass base, and examined nine parameters: light transmittance, degree of conversion (DC), maximum polymerisation rate (R max ), time to reach R max , linear shrinkage, shrinkage stress (PSS), maximum PSS rate, time to reach maximum PSS rate, and depth of cure. Cu-MBGN without silica accelerated polymerisation, reduced light transmission, and had the highest DC (58.8 ± 0.9%) and R max (9.8 ± 0.2%/s), but lower shrinkage (3 ± 0.05%) and similar PSS (0.89 ± 0.07 MPa) versus the inert reference (0.83 ± 0.13 MPa). Combined Cu-MBGN and silica slowed the R max and achieved a similar DC but resulted in higher shrinkage. However, using a combined 5 wt.% Cu-MBGN and silica, the PSS resembled that of the inert reference. The synergistic action of 5 wt.% Cu-MBGN and silanised silica in combination with silanised barium glass resulted in a material with the highest likelihood for dental applications in future.

Nanotechnology has become an emerging research field with numerous biomedical scientific applications. Silver possesses bactericidal activities that have been harnessed for centuries; however, there is a concern about the toxic effects of silver nanoparticles. This paper aims to provide an overview of silver-treated dental implants and discuss their potential to reduce the prevalence of peri-implant diseases. An electronic search was performed using PubMed. After screening, data extraction was performed on the 45 remaining articles using inclusion and exclusion criteria. Most of the articles demonstrated that silver nanoparticles embedded in a coating layer and/or on surface-treated titanium exhibit sound antibacterial effects and biocompatibility. Most of the reviewed studies revealed that silver nanoparticles on dental implant surfaces reduced cytotoxicity but provided a prolonged antibacterial effect. The cytotoxicity and antibacterial effect are closely linked to how the silver nanoparticles are released from the titanium surfaces, where a slower release increases cell viability and proliferation. However, to improve the clinical translation, there is still a need for more studies, especially evaluating the long-term systemic effects and studies recreating the conditions in the oral cavity.

Combining biomaterial scaffolds with cells serves as a promising strategy for engineering critical size defects; however, homogenous cellular growth within large scaffolds is challenging. Mechanical stimuli can enhance bone regeneration by modulating cellular growth and differentiation. Here, we compare dynamic seeding in a perfusion flow bioreactor with static seeding for a synthetic bone scaffold for up to 21 days using the cell line MC3T3-E1 and primary human osteoblast, confocal laser scanning microscopy, and real-time reverse transcriptase-polymerase chain reaction. The secretion of bone-related proteins was quantified using multiplex immunoassays. Dynamic culture improved cellular distribution through the TiO 2 scaffold and induced a five-fold increase in cell number after 21 days. The relative mRNA expression of osteopontin of MC3T3-E1 was 40-fold enhanced after 7 and 21 days at a flow rate of 0.08 mL/min, and that of collagen type I alpha I expression was 18-fold after 21 days. A flow rate of 0.16 mL/min was 10-fold less effective. Dynamic culture increased the levels of dickkopf-related protein 1 (60-fold), osteoprotegrin (29-fold), interleukin-6 (23-fold), interleukin-8 (36-fold), monocyte chemoattractant protein 1 (28-fold) and vascular endothelial growth factor (6-fold) in the medium of primary human osteoblasts after 21 days compared to static seeding. The proposed method may have clinical potential for bone tissue engineering.

Biocompatible fibrous scaffolds based on highly deacetylated chitosan were fabricated using high-throughput solution blow spinning. Scanning electron microscopy analysis revealed that the chitosan nanofiber scaffolds had ultrafine and continuous fibers (300-1200 nm) with highly interconnected porous structures (30-75% porosity), mimicking some aspects of the native extracellular matrix in skin tissue. Post-treatment of as-spun nanofibers with aqueous potassium carbonate solution resulted in a fibrous scaffold with a high chitosan content that retained its fibrous structural integrity for cell culture. Analysis of the mechanical properties of the chitosan nanofiber scaffolds in both dry and wet conditions showed that their strength and durability were sufficient for wound dressing applications. Significantly, the wet scaffold underwent remarkable elastic deformation during stretch such that the elongation at break dramatically increased to up to 44% of its original length, showing wavy fiber morphology near the break site. The culture of normal human dermal fibroblast cells onto scaffolds for 1-14 days demonstrated that the scaffolds were highly compatible and a suitable platform for cell adhesion, viability, and proliferation. Secretion profiles of wound healing-related proteins to the cell culture medium demonstrated that chitosan fibers were a promising scaffold for wound healing applications. Overall, the dense fibrous network with high porosity of the chitosan nanofiber scaffold and their mechanical properties indicate that they could be used to design and fabricate new materials that mimic the epidermis layer of natural skin., (Copyright © 2022. Published by Elsevier B.V.)

Magnesium (Mg)-based degradable alloys have attracted substantial attention for tissue engineering applications due to their biodegradability and potential for avoiding secondary removal surgeries. However, insufficient data in the existing literature regarding Mg's corrosion and gas formation after implantation have delayed its wide clinical application. Since the surface properties of degradable materials constantly change after contact with body fluid, monitoring the behaviour of Mg in phantoms or buffer solutions could provide some information about its physicochemical surface changes over time. Through surface analysis and spectroscopic analysis, we aimed to investigate the structural and functional properties of degradable disks. Since bubble formation may lead to inflammation and change pH, monitoring components related to acidosis near the cells is essential. To study the bubble formation in cell culture media, we used a newly developed Mg alloy (based on Mg, zinc, and calcium), pure Mg, and commercially available grade 2 Titanium (Ti) disks in Dulbecco's Modified Eagle Medium (DMEM) solution to observe their behaviour over ten days of immersion. Using surface analysis and the information from near-infrared spectroscopy (NIRS), we concluded on the conditions associated with the medical risks of Mg alloy disintegration. NIRS is used to investigate the degradation behaviour of Mg-based disks in the cell culture media, which is correlated with the surface analysis where possible.

Developing new implant surfaces with anti-adhesion bacterial properties used for medical devices remains a challenge. Here we describe a novel study investigating nanotopography influences on bacterial adhesion on surfaces with controlled interspatial nanopillar distances. The surfaces were coated with proteins (fibrinogen, collagen, serum and saliva) prior to E. coli-WT adhesion under flow conditions. PiFM provided chemical mapping and showed that proteins adsorbed both between and onto the nanopillars with a preference for areas between the nanopillars. E. coli-WT adhered least to protein-coated areas with low surface nanopillar coverage, most to surfaces coated with saliva, while human serum led to the lowest adhesion. Protein-coated nanostructured surfaces affected the adhesion of E. coli-WT .

Fabrication of vascularized large-scale constructs for regenerative medicine remains elusive since most strategies rely solely on cell self-organization or overly control cell positioning, failing to address nutrient diffusion limitations. We propose a modular and hierarchical tissue-engineering strategy to produce bonelike tissues carrying signals to promote prevascularization. In these 3D systems, disc-shaped microcarriers featuring nanogrooved topographical cues guide cell behavior by harnessing mechanotransduction mechanisms. A sequential seeding strategy of adipose-derived stromal cells and endothelial cells is implemented within compartmentalized, liquefied-core macrocapsules in a self-organizing and dynamic system. Importantly, our system autonomously promotes osteogenesis and construct's mineralization while promoting a favorable environment for prevascular-like endothelial organization. Given its modular and self-organizing nature, our strategy may be applied for the fabrication of larger constructs with a highly controlled starting point to be used for local regeneration upon implantation or as drug-screening platforms.

Background: A brush made of chitosan has shown to be an effective and harmless device for non-surgical treatment of mild to moderate peri-implantitis. To date, no study has evaluated the use of a chitosan brush in the non-surgical treatment of residual pockets in periodontal treatment., Methods: Seventy-eight patients with periodontitis were included in this multicenter, randomized, examiner-blind clinical trial of 6 months duration. Patients with residual probing pocket depth (PPD) of ≥5 mm and ≤7 mm following previous active periodontal treatment were included. Patients were assigned either subgingival treatment with curettes (control) or an oscillating chitosan brush (test). Changes in bleeding on probing (BoP) and PPD between baseline and terminal evaluation at 6 months were evaluated., Results: A significant reduction in both PPD and BoP was seen within both groups. There was no significant difference in BoP between test and control groups after 6 months, but the reduction in PPD was significantly improved in the test group (P ≤ 0.01). The combined outcome of no BOP and PPD ≤4 mm was significantly better in the test group (P ≤ 0.01). No adverse reactions were seen., Conclusion: Treatment of residual periodontal pockets (PPD = 5 to 7 mm) with a chitosan brush disclosed equal or better clinical results as compared to regular curettes. This study supports that a chitosan brush can be used for subgingival biofilm removal and soft tissue curretage in the treatment of periodontitis., (© 2021 The Authors. Journal of Periodontology published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.)

This article focuses on preclinical studies and reviews the available evidence from the literature on dental implant and abutment materials in the last decade. Specifically, different peri-implantitis materials and how surface modifications may affect the peri-implant soft-tissue seal and subsequently delay or hinder peri-implantitis are examined. This review analyzed more than 30 studies that were Randomized Controlled Trials (RCTs), Controlled Clinical Trials (CCTs), or prospective case series (CS) with at least six months of follow-up. Meta-analyses were performed to make a comparison between different implant materials (titanium vs. zirconia), including impact on bone changes, probing depth, plaque levels, and peri-implant mucosal inflammation, as well as how the properties of the implant material and surface modifications would affect the peri-implant soft-tissue seal and peri-implant health conditions. However, there was no clear evidence regarding whether titanium is better than other implant materials. Clinical evidence suggests no difference between different implant materials in peri-implant bone stability. The metal analysis offered a statistically significant advantage of zirconia implants over titanium regarding developing a favorable response to the alveolar bone.

Musculoskeletal defects are an enormous healthcare burden and source of pain and disability for individuals. With an aging population, the proportion of individuals living with these medical indications will increase. Simultaneously, there is pressure on healthcare providers to source efficient solutions, which are cheaper and less invasive than conventional technology. This has led to an increased research focus on hydrogels as highly biocompatible biomaterials that can be delivered through minimally invasive procedures. This review will discuss how hydrogels can be designed for clinical translation, particularly in the context of the new European Medical Device Regulation (MDR). We will then do a deep dive into the clinically used hydrogel solutions that have been commercially approved or have undergone clinical trials in Europe or the United States. We will discuss the therapeutic mechanism and limitations of these products. Due to the vast application areas of hydrogels, this work focuses only on treatments of cartilage, bone, and the nucleus pulposus. Lastly, the main steps toward clinical translation of hydrogels as medical devices are outlined. We suggest a framework for how academics can assist small and medium MedTech enterprises conducting the initial clinical investigation and post-market clinical follow-up required in the MDR. It is evident that the successful translation of hydrogels is governed by acquiring high-quality pre-clinical and clinical data confirming the device mechanism of action and safety., Competing Interests: M.M.S. is co‐inventor on patent application 1911235.8 submitted by Imperial College London, related to ultrasound‐triggered liposome payload release., (© 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

Malignant bone tumors are usually treated by resection of tumor tissue followed by filling of the bone defect with bone graft substitutes. Polymethylmethacrylate (PMMA) cement is the most commonly used bone substitute in clinical orthopedics in view of its reliability. However, the dense nature of PMMA renders this biomaterial unsuitable for local delivery of chemotherapeutic drugs to limit the recurrence of bone tumors. Here, we introduce porosity into PMMA cement by adding carboxymethylcellulose (CMC) to facilitate such local delivery of chemotherapeutic drugs, while retaining sufficient mechanical properties for bone reconstruction in load-bearing sites. Our results show that the mechanical strength of PMMA-based cements gradually decreases with increasing CMC content. Upon incorporation of ≥3% CMC, the PMMA-based cements released up to 18% of the loaded cisplatin, in contrast to cements containing lower amounts of CMC which only released less than 2% of the cisplatin over 28 days. This release of cisplatin efficiently killed osteosarcoma cells in vitro and the fraction of dead cells increased to 91.3% at day 7, which confirms the retained chemotherapeutic activity of released cisplatin from these PMMA-based cements. Additionally, tibias filled with PMMA-based cements containing up to 3% of CMC exhibit comparable compressive strengths as compared to intact tibias. In conclusion, we demonstrate that PMMA cements can be rendered therapeutically active by introducing porosity using CMC to allow for release of cisplatin without compromising mechanical properties beyond critical levels. As such, these data suggest that our dual-functional PMMA-based cements represent a viable treatment option for filling bone defects after bone tumor resection in load-bearing sites., (© 2022 The Authors.)

Ameloblastoma is a benign, epithelial cancer of the jawbone, which causes bone resorption and disfigurement to patients affected. The interaction of ameloblastoma with its tumour stroma drives invasion and progression. We used stiff collagen matrices to engineer active bone forming stroma, to probe the interaction of ameloblastoma with its native tumour bone microenvironment. This bone-stroma was assessed by nano-CT, transmission electron microscopy (TEM), Raman spectroscopy and gene analysis. Furthermore, we investigated gene correlation between bone forming 3D bone stroma and ameloblastoma introduced 3D bone stroma. Ameloblastoma cells increased expression of MMP-2 and -9 and RANK temporally in 3D compared to 2D. Our 3D biomimetic model formed bone nodules of an average surface area of 0.1 mm 2 and average height of 92.37 [Formula: see text] 7.96 μm over 21 days. We demonstrate a woven bone phenotype with distinct mineral and matrix components and increased expression of bone formation genes in our engineered bone. Introducing ameloblastoma to the bone stroma, completely inhibited bone formation, in a spatially specific manner. Multivariate gene analysis showed that ameloblastoma cells downregulate bone formation genes such as RUNX2. Through the development of a comprehensive bone stroma, we show that an ameloblastoma tumour mass prevents osteoblasts from forming new bone nodules and severely restricted the growth of existing bone nodules. We have identified potential pathways for this inhibition. More critically, we present novel findings on the interaction of stromal osteoblasts with ameloblastoma., (© 2021. The Author(s).)

Background: Insufficient bone volume around an implant is a common obstacle when dental implant treatment is considered. Limited vertical or horizontal bone dimensions may lead to exposed implant threads following placement or a gap between the bone and implant. This is often addressed by bone augmentation procedures prior to or at the time of implant placement. This study evaluated bone healing when a synthetic TiO 2 block scaffold was placed in circumferential peri-implant defects with buccal fenestrations., Methods: The mandibular premolars were extracted and the alveolar bone left to heal for 4 weeks prior to implant placement in six minipigs. Two cylindrical defects were created in each hemi-mandible and were subsequent to implant placement allocated to treatment with either TiO 2 scaffold or sham in a split mouth design. After 12 weeks of healing time, the samples were harvested. Microcomputed tomography (MicroCT) was used to investigate defect fill and integrity of the block scaffold. Distances from implant to bone in vertical and horizontal directions, percentage of bone to implant contact and defect fill were analysed by histology., Results: MicroCT analysis demonstrated no differences between the groups for defect fill. Three of twelve scaffolds were partly fractured. At the buccal sites, histomorphometric analysis demonstrated higher bone fraction, higher percentage bone to implant contact and shorter distance from implant top to bone 0.5 mm lateral to implant surface in sham group as compared to the TiO 2 group., Conclusions: This study demonstrated less bone formation with the use of TiO 2 scaffold block in combination with implant placement in cylindrical defects with buccal bone fenestrations, as compared to sham sites., (© 2021. The Author(s).)

Today, substantial attention is given to biomaterial strategies for bone regeneration, and among them, there is a growing interest in using immunomodulatory biomaterials. The ability of a biomaterial to induce neo vascularization and macrophage polarization is a major factor in defining its success. Magnesium (Mg)-based degradable alloys have attracted significant attention for bone regeneration owing to their biodegradability and potential for avoiding secondary removal surgeries. However, there is insufficient evidence in the literature regarding the early inflammatory responses to these alloys in vivo. In this study, we investigated the early body responses to Mg-0.45wt%Zn-0.45wt%Ca pin-shaped alloy (known as ZX00 alloy) in rat femora 2, 5, and 10 days after implantation. We used 3D micro computed tomography (µCT), histological, immunohistochemical, histomorphometrical, and small angle X-ray scattering (SAXS) analyses to study new bone formation, early macrophage polarization, neo vascularization, and bone quality at the implant bone interface. The expression of macrophage type 2 biological markers increased significantly after 10 days of Mg alloy implantation, indicating its potential in stimulating macrophage polarization. Our biomineralization results using µCT as well as histological stained sections did not indicate any statistically significant differences between different time points for both groups. The activity of alkaline phosphatase (ALP) and Runt-related transcription factor 2 (Runx 2) biological markers decreased significantly for Mg group, indicating less osteoblast activity. Generally, our results supported the potential of ZX00 alloy to enhance the expression of macrophage polarization in vivo; however, we could not observe any statistically significant changes regarding biomineralization., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Objectives: Evaluate the dimensions and morphology of peri-implant tissues around a modified dental implant designed with tissue level connection and a convergent transmucosal neck, when compared with a conventional bone level implant connected to a cylindrical machined titanium abutment., Material and Methods: Eight experimental animals were used for this in vivo investigation, in whom 16 test and 16 control implants were placed following a random allocation sequence. The following histological outcomes at 4 and 12 weeks were evaluated: morphology of peri-implant tissues, the soft tissue height and thickness, the horizontal and vertical bone remodeling, and the bone to implant contact (BIC)., Results: In both early (4 weeks) and late (12 weeks) healing times, there were no statistically significant differences between test and control implants, with respect to the overall height and thickness of the peri-implant hard and soft tissues. There was a tendency toward a more coronal free gingival margin (I-FGM) at the buccal aspect of test when compared to control implants (at 4 weeks, difference of 0.97 mm (p = .572) and 0.30 mm (p = 1.000) at 12 weeks). Similarly, there was a tendency toward a more coronal position of the first bone to implant contact (I-B) at the buccal aspect of test as compared to control implants (1.08 mm (p = 0.174) at 4 weeks and 0.83 mm (p = 0.724) at 12 weeks)., Conclusions: Hard and soft tissue healing occurred at both implant types with no statistically significant differences. Test implants tended to present a more coronal gingival margin (FGM) and first bone to implant contact (B)., (© 2021 The Authors. Clinical Oral Implants Research published by John Wiley & Sons Ltd.)