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SDF-1/CXCL12 is a unique chemotactic factor with multiple functions on various types of precursor cells, all carrying the cognate receptor CXCR4. Whereas individual biological functions of SDF-1/CXCL12 have been well documented, practical applications in medicine are insufficiently studied. This is explained by the complex multifunctional biology of SDF-1 with systemic and local effects, critical dependence of SDF-1 activity on aminoterminal proteolytic processing and limited knowledge of applicable modulators of its activity. We here present new insights into modulation of SDF-1 activity in vitro and in vivo by a macromolecular compound, chlorite-oxidized oxyamylose (COAM). COAM prevented the proteolytic inactivation of SDF-1 by two inflammation-associated proteases: matrix metalloproteinase-9/MMP-9 and dipeptidylpeptidase IV/DPPIV/CD26. The inhibition of proteolytic inactivation was functionally measured by receptor-mediated effects, including intracellular calcium mobilization, ERK1/2 phosphorylation, receptor internalization and chemotaxis of CXCR4-positive cells. Protection of SDF-1/CXCL12 against proteolysis was dependent on electrostatic COAM-SDF-1 interactions. By in vivo experiments in mice, we showed that the combination of COAM with SDF-1 delivered through physiological fibrin hydrogel had beneficial effect for the healing of skin wounds. Collectively, we show that COAM protects SDF-1 from proteolytic inactivation, maintaining SDF-1 biological activities. Thus, protection from proteolysis by COAM represents a therapeutic strategy to prolong SDF-1 bioavailability for wound healing applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Pereira, EzEldeen, Ugarte-Berzal, Vandooren, Martens, Gouwy, Ganseman, Van Damme, Matthys, Vranckx, Proost and Opdenakker.)

Introduction: As personalized medicine advances, there is an escalating need for sophisticated tools to understand complex biomechanical phenomena in clinical research. Recognizing a significant gap, this study pioneers the development of patient-specific in silico models for tooth autotransplantation (TAT), setting a new standard for predictive accuracy and reliability in evaluating TAT outcomes., Methods: Development of the models relied on 6 consecutive cases of young patients (mean age 11.66 years ± 0.79), all undergoing TAT procedures. The development process involved creating detailed in silico replicas of patient oral structures, focusing on transplanting upper premolars to central incisors. These models underpinned finite element analysis simulations, testing various masticatory and traumatic scenarios., Results: The models highlighted critical biomechanical insights. The finite element models indicated homogeneous stress distribution in control teeth, contrasted by shape-dependent stress patterns in transplanted teeth. The surface deviation in the postoperative year for the transplanted elements showed a mean deviation of 0.33 mm (±0.28), significantly higher than their contralateral counterparts at 0.05 mm (±0.04)., Conclusions: By developing advanced patient-specific in silico models, we are ushering in a transformative era in TAT research and practice. These models are not just analytical tools; they are predictive instruments capturing patient uniqueness, including anatomical, masticatory, and tissue variables, essential for understanding biomechanical responses in TAT. This foundational work paves the way for future studies, where applying these models to larger cohorts will further validate their predictive capabilities and influence on TAT success parameters., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Incorporation of growth factors, signaling molecules and drugs can be vital for the success of tissue engineering in complex structures such as the dentoalveolar region. This has led to the development of a variety of drug release systems. This study aimed to develop pNIPAM-methylcellulose microgels with different synthesis parameters based on a 2 3 full factorial design of experiments for this application. Microgel properties, including volume phase transition temperature (VPTT), hydrodynamic size, drug loading and release, and cytocompatibility were systematically evaluated. The results demonstrated successful copolymerization and development of the microgels, a hydrodynamic size ranging from ∼200 to ∼500 nm, and VPTT in the range of 34-39 °C. Furthermore, loading of genipin, capable of inducing odontoblastic differentiation, and its sustained release over a week was shown in all formulations. Together, this can serve as a solid basis for the development of tunable drug-delivering pNIPAM-methylcellulose microgels for specific tissue engineering applications., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

While available treatments have addressed a variety of complications in the dentoalveolar region, associated challenges have resulted in exploration of tissue engineering techniques. Often, scaffold biomaterials with specific properties are required for such strategies to be successful, development of which is an active area of research. This study focuses on the development of a copolymer of poly (N-isopropylacrylamide) (pNIPAM) and chitosan, used for 3D printing of scaffolds for dentoalveolar regeneration. The synthesized material was characterized by Fourier transform infrared spectroscopy, and the possibility of printing was evaluated through various printability tests. The rate of degradation and swelling was analyzed through gravimetry, and surface morphology was characterized by scanning electron microscopy. Viability of dental pulp stem cells seeded on the scaffolds was evaluated by live/dead analysis and DNA quantification. The results demonstrated successful copolymerization, and three formulations among various synthesized formulations were successfully 3D printed. Up to 35% degradability was confirmed within 7 days, and a maximum swelling of approximately 1200% was achieved. Furthermore, initial assessment of cell viability demonstrated biocompatibility of the developed scaffolds. While further studies are required to achieve the tissue engineering goals, the present results tend to indicate that the proposed hydrogel might be a valid candidate for scaffold fabrication serving dentoalveolar tissue engineering through 3D printing.

Introduction: Understanding the healing process of dental pulp after tooth autotransplantation (TAT) and regenerative endodontic treatment (RET) of immature teeth is important both clinically and scientifically. This study aimed to characterize the pattern of dental pulp healing in human teeth that underwent TAT and RET using state-of-the-art imaging techniques., Materials and Methods: This study examined 4 human teeth, 2 premolars that underwent TAT, and 2 central incisors that received RET. The premolars were extracted after 1 year (case 1) and 2 years (case 2) due to ankylosis, while the central incisors were extracted after 3 years (cases 3 and 4) for orthodontic reasons. Nanofocus x-ray computed tomography was used to image the samples before being processed for histological and immunohistochemical analysis. Laser scanning confocal second harmonic generation imaging (SHG) was used to examine the patterns of collagen deposition. A maturity-matched premolar was included as a negative control for the histological and SHG analysis., Results: Analysis of the 4 cases revealed different patterns of dental pulp healing. Similarities were observed in the progressive obliteration of the root canal space. However, a striking loss of typical pulpal architecture was observed in the TAT cases, while a pulp-like tissue was observed in one of the RET cases. Odontoblast-like cells were observed in cases 1 and 3., Conclusions: This study provided insights into the patterns of dental pulp healing after TAT and RET. The SHG imaging sheds light on the patterns of collagen deposition during reparative dentin formation., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The biomechanics of transplanted teeth remain poorly understood due to a lack of models. In this context, finite element (FE) analysis has been used to evaluate the influence of occlusal morphology and root form on the biomechanical behavior of the transplanted tooth, but the construction of a FE model is extremely time-consuming. Model order reduction (MOR) techniques have been used in the medical field to reduce computing time, and the present study aimed to develop a reduced model of a transplanted tooth using the higher-order proper generalized decomposition method. The FE model of a previous study was used to learn von Mises root stress, and axial and lateral forces were used to simulate different occlusions between 75 and 175N. The error of the reduced model varied between 0.1% and 5.9% according to the subdomain, and was the highest for the highest lateral forces. The time for the FE simulation varied between 2.3 and 7.2 h. In comparison, the reduced model was built in 17s and interpolation of new results took approximately 2.10 -2 s. The use of MOR reduced the time for delivering the root stresses by a mean 5.9 h. The biomechanical behavior of a transplanted tooth simulated by FE models was accurately captured with a significant decrease of computing time. Future studies could include using jaw tracking devices for clinical use and the development of more realistic real-time simulations of tooth autotransplantation surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest, (Copyright © 2023 Lahoud, Badrou, Ducret, Farges, Jacobs, Bel-Brunon, EzEldeen, Blal and Richert.)

The aim of this study was to compare the quantification of hard-tissue debris by using micro-computed tomography (micro-CT) and nano-focus computed tomography (nano-CT) after root canal instrumentation. Ten mandibular molars containing an isthmus in the mesial root were scanned in a SkyScan 1172 micro-CT device with a voxel size of 12.8 µm and in a NanoTom nano-CT device with 5.5 µm. The mesial root canals were irrigated with 5 mL of saline solution at the orifice level, instrumented with Reciproc R25 files and a second scanning was performed by micro-CT and nano-CT devices for post-instrumentation images. DataViewer software was used for registering the pre- and post-operative micro-CT and nano-CT images. The root canal and the debris were segmented for quantitative analysis of the volume of the canal and volume of debris using CTAn software. Statistical analysis was performed using the T test for comparison between volume of the canal after instrumentation and volume of debris in both image modalities. The level of significance was set at p < 0.05. Nano-CT images showed higher values of debris when compared with micro-CT (p < 0.05) after root canal instrumentation. No difference was observed between the volume of the root canal after instrumentation in the two imaging methods used (p > 0.05). Nano-CT technology can be recommended as a more precise method for quantitative analysis of hard-tissue debris. Moreover, in Endodontic research it is a promising method, as it is capable of providing higher spatial and contrast resolution, faster scanning and higher image quality.

Oral health is essential for a good overall health. Dento-alveolar conditions have a high prevalence, ranging from tooth decay periodontitis to alveolar bone resorption. However, oral tissues exhibit a limited regenerative capacity, and full recovery is challenging. Therefore, regenerative therapies for dento-alveolar tissue (e.g., alveolar bone, periodontal membrane, dentin-pulp complex) have gained much attention, and novel approaches have been proposed in recent decades. This review focuses on the cells, biomaterials and the biofabrication methods used to develop therapies for tooth root bioengineering. Examples of the techniques covered are the multitude of additive manufacturing techniques and bioprinting approaches used to create scaffolds or tissue constructs. Furthermore, biomaterials and stem cells utilized during biofabrication will also be described for different target tissues. As these new therapies gradually become a reality in the lab, the translation to the clinic is still minute, with a further need to overcome multiple challenges and broaden the clinical application of these alternatives., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Wound healing is a complex process to restore homeostasis after injury and insufficient skin wound healing is a considerable problem in medicine. Whereas many attempts of regenerative medicine have been made for wound healing with growth factors and cell therapies, simple pharmacological and immunological studies are lagging behind. We investigated how fibrin hydrogels modulate immune cells and molecules in skin wound healing in mice., Methods: Physiological fibrin hydrogels (3.5 mg/mL fibrinogen) were generated, biophysically analyzed for stiffness and protein contents and were structurally studied by scanning electron microscopy. Physiological fibrin hydrogels were applied to full thickness skin wounds and, after 3 days, cells and molecules in wound tissues were analyzed. Leukocytes, endothelial cells, fibroblasts and keratinocytes were explored with the use of Flow Cytometry, whereas cytokines and matrix metalloproteinases were analyzed with the use of qPCR, ELISAs and zymography. Skin wound healing was analyzed microscopically at day 3, macroscopically followed daily during repair in mice and compared with commercially available fibrin sealant Tisseel., Results: Exogenous fibrin at physiological concentrations decreased neutrophil and increased non-classical Ly6Clow monocyte and resolutive macrophage (CD206 + and CX3CR1 + ) populations, at day 3 after injury. Fibrin hydrogel reduced the expression of pro-inflammatory cytokines and increased IL-10 levels. In line with these findings, gelatinase B/MMP-9 was decreased, whereas gelatinase A/MMP-2 levels remained unaltered. Frequencies of dermal endothelial cells, fibroblasts and keratinocytes were increased and keratinocyte migration was enhanced by fibrin hydrogel. Importantly, physiological fibrin accelerated the healing of skin wounds in contrast to the highly concentrated fibrin sealant Tisseel, which delayed wound repair and possessed a higher fiber density., Conclusion: Collectively, we show that adding a tailored fibrin hydrogel scaffold to a wound bed positively influences the healing process, modulating leukocyte populations and inflammatory responses towards a faster wound repair., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pereira, EzEldeen, Ugarte-Berzal, Martens, Malengier-Devlies, Vandooren, Vranckx, Matthys and Opdenakker.)

Dentoalveolar tissue engineering is an emerging yet challenging field, considering the lack of suitable materials and difficulty to produce patient-specific hydrogel scaffolds. The present paper aims to produce a 3D printable and tuneable biomaterial by copolymerizing a synthesized water-soluble chitosan derivative called maleic anhydride grafted chitosan (MA-C) with gelatin using genipin, a natural crosslinking agent. Development and testing of this material for 3D printing, degradation, and swelling demonstrated the ability to fabricate scaffolds with controlled physical properties based on pre-determined designs. The MA-C-gelatin copolymer demonstrated excellent biocompatibility, which was verified by analyzing the viability, growth and proliferation of human dental pulp stem cells seeded on MA-C-gelatin constructs through live/dead, alamar blue and DNA quantification assays. Based on the present findings, the proposed material might be a suitable candidate for dentoalveolar tissue engineering, while further research is required to achieve this goal., (Copyright © 2022. Published by Elsevier Ltd.)

The dental practice has largely evolved in the last 50 years following a better understanding of the biomechanical behaviour of teeth and its supporting structures, as well as developments in the fields of imaging and biomaterials. However, many patients still encounter treatment failures; this is related to the complex nature of evaluating the biomechanical aspects of each clinical situation due to the numerous patient-specific parameters, such as occlusion and root anatomy. In parallel, the advent of cone beam computed tomography enabled researchers in the field of odontology as well as clinicians to gather and model patient data with sufficient accuracy using image processing and finite element technologies. These developments gave rise to a new precision medicine concept that proposes to individually assess anatomical and biomechanical characteristics and adapt treatment options accordingly. While this approach is already applied in maxillofacial surgery, its implementation in dentistry is still restricted. However, recent advancements in artificial intelligence make it possible to automate several parts of the laborious modelling task, bringing such user-assisted decision-support tools closer to both clinicians and researchers. Therefore, the present narrative review aimed to present and discuss the current literature investigating patient-specific modelling in dentistry, its state-of-the-art applications, and research perspectives., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The recent advances in the field of cell-based therapeutics open promising perspectives for oral tissue regeneration. The development of large animal models, which overcome the limits of the rodent models and allow to emulate clinical situations, is crucial for the validation of regenerative strategies to move toward clinical application. Currently, porcine, canine, and ovine models are mainly developed for oral regeneration and their specific characteristics have an impact on the outcomes of the studies. Thus, this systematic review investigates the application of porcine, canine, and ovine models in present cell-based oral regeneration, according to the species characteristics and the targeted tissue to regenerate. A customized search of PubMed, EMBASE, Scopus, and Web of Science databases from January 2015 to March 2020 was conducted. Relevant articles about cell-based oral tissues engineering in porcine, canine, and ovine models were evaluated. Among the evaluated articles, 58 relevant studies about cell-based oral regeneration in porcine, canine, and ovine models matched the eligibility criteria and were selected for full analysis. Porcine models, the most similar species with humans, were mostly used for bone and periodontium regeneration; tooth regeneration was reported only in pig, except for one study in dog. Canine models were the most transversal models, successfully involved for all oral tissue regeneration and notably in implantology. However, differences with humans and ethical concerns affect the use of these models. Ovine models, alternative to porcine and canine ones, were mainly used for bone and, scarcely, periodontium regeneration. The anatomy and physiology of these animals restrain their involvement. If consistency was found in defect specificities and cell trends among different species animal models of bone, dentin-pulp complex, or tooth regeneration, variability appeared in periodontium. Regeneration assessment methods were more elaborate in porcines and canines than in ovines. Risk of bias was low for selection, attrition and reporting, but unclear for performance and detection. Overall, if none of the large animal models can be considered an ideal one, they are of deemed importance for oral cell-based tissue engineering and researchers should consider their relevance to establish favorable conditions for a given preclinical cell-based therapeutics. Impact statement This systematic review investigates porcine, canine, and ovine models for current oral cell-based regeneration procedures, and researchers could refer to it for the choice of the most pertinent preclinical model for a given cell-based therapeutics.

Objectives: The present study aims to describe the relationship between upper first molar roots and maxillary sinus, for the first time with a truly three-dimensional approach., Methods: From a retrospective cone-beam computed tomography (CBCT) sample of the upper jaw, a total of 105 upper first molars in contact with maxillary sinus from 74 patients (male 24, female 50, mean age 42) were included in the present study. Segmentation of the upper first molar and maxillary sinus in CBCT was performed utilizing a semiautomatic livewire segmentation tool in MeVisLab v.3.1. The segmentations were analyzed in 3-matic Medical 20.0 for root volume and the contact area between upper first molar roots and maxillary sinus. Analysis of variance test was applied to detect statistically significant differences between the roots., Results: The palatal root had the largest contact area with maxillary sinus 27.8 ± 21.4 mm 2 (20% of the root area) followed by the mesiobuccal 20.5 ± 17.9 mm 2 (17% of the root area) and distobuccal root 13.7 ± 12 mm 2 (14% of the root area). A significant difference in the contact area of the different roots of the upper first molar was seen., Conclusions: This study showed that 70% of the upper first molars were in contact with the maxillary sinus. The palatal root had on average a fifth of its root surface in contact with the sinus, while for mesiobuccal this was a sixth of its root surface and distobuccal roots this was somewhat less. The true 3D relationship could help to better understand maxillary anatomy in relation to occurring pathologies and treatment planning in this area., (© 2022 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

Although current treatments can successfully address a wide range of complications in the dentoalveolar region, they often still suffer from drawbacks and limitations, resulting in sub-optimal treatments for specific problems. In recent decades, significant progress has been made in the field of tissue engineering, aiming at restoring damaged tissues via a regenerative approach. Yet, the translation into a clinical product is still challenging. Novel technologies such as bioprinting have been developed to solve some of the shortcomings faced in traditional tissue engineering approaches. Using automated bioprinting techniques allows for precise placement of cells and biological molecules and for geometrical patient-specific design of produced biological scaffolds. Recently, bioprinting has also been introduced into the field of dentoalveolar tissue engineering. However, the choice of a suitable material to encapsulate cells in the development of so-called bioinks for bioprinting dentoalveolar tissues is still a challenge, considering the heterogeneity of these tissues and the range of properties they possess. This review, therefore, aims to provide an overview of the current state of the art by discussing the progress of the research on materials used for dentoalveolar bioprinting, highlighting the advantages and shortcomings of current approaches and considering opportunities for further research.

Objectives: This study investigated the impact of micro-computed tomography (micro-CT)-based voxel size on the analysis of material/dentin interface voids and thickness of different endodontic cements., Materials and Methods: Following root-end resection and apical preparation, maxillary premolars were filled with mineral trioxide aggregate (MTA), Biodentine, and intermediate restorative material (IRM) ( n = 24). The samples were scanned using micro-CT (SkyScan 1272; Bruker) and the cement/dentin interface and thickness of materials were evaluated at voxel sizes of 5, 10, and 20 µm. Analysis of variance and the Tukey test were conducted, and the degree of agreement between different voxel sizes was evaluated using the Bland and Altman method ( p < 0.05)., Results: All materials showed an increase in thickness from 5 to 10 and 20 µm ( p < 0.05). When evaluating the interface voids, materials were similar at 5 µm ( p > 0.05), while at 10 and 20 µm Biodentine showed the lowest percentage of voids ( p < 0.05). A decrease in the interface voids was observed for MTA and IRM at 20 µm, while Biodentine showed differences among all voxel sizes ( p < 0.05). The Bland-Altman plots for comparisons among voxel sizes showed the largest deviations when comparing images between 5 and 20 µm., Conclusions: Voxel size had an impact on the micro-CT evaluation of thickness and interface voids of endodontic materials. All cements exhibited an increase in thickness and a decrease in the void percentage as the voxel size increased, especially when evaluating images at 20 µm., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2022. The Korean Academy of Conservative Dentistry.)

The aim of this study was to compare the efficacy of UAI with ESI, sonic activation with Eddy ® and syringe irrigation in removing debris, and dentin removal during canal irrigation. Twenty-four mandibular molars containing isthmus type V and with a mean curvature of 32.5° were instrumented and divided into three groups for final irrigation: UAI with ESI, sonic activation with Eddy and syringe irrigation. The samples were scanned in a SkyScan 1172 micro-CT device for pre-, post-instrumentation and post-irrigation images and analysis of dentin removal. Statistical analysis was performed using Wilcoxon, Kruskal-Wallis and Dunn tests. UAI and sonic activation significantly improved debris removal (P < 0.05). No significant difference was observed regarding dentin removal between the groups (P > 0.05), although higher values were found for UAI. Sonic activation with Eddy ® showed to be an effective and safe device since it was able to remove debris without causing damage to the canal walls., (© 2021 Australian Society of Endodontology Inc.)

Introduction: The aim of this nonrandomized, multicenter controlled clinical trial was to evaluate the impact of leukocyte-platelet-rich fibrin (LPRF) on regenerative endodontic procedures (REPs) of immature permanent teeth in terms of periapical bone healing (PBH) and further root development (RD)., Methods: Healthy patients between 6-25 years with an inflamed or necrotic immature permanent tooth were included and divided between the test (= REP + LPRF) and control (= REP-LPRF) group depending on their compliance and the clinical setting (university hospital or private practice). After receiving REP ± LPRF, the patients were recalled after 3, 6, 12, 24, and 36 months. At each recall session, the teeth were clinically and radiographically (by means of a periapical radiograph [PR]) evaluated. A cone-beam computed tomographic (CBCT) imaging was taken preoperatively and 2 and 3 years postoperatively. PBH and RD were quantitatively and qualitatively assessed., Results: Twenty-nine teeth with a necrotic pulp were included, from which 23 (9 test and 14 control) were analyzed. Three teeth in the test group had a flare-up reaction in the first year after REP. Except for 2 no shows, all the analyzed teeth survived up to 3 years after REP, and, in case of failure, apexification preserved them. Complete PBH was obtained in 91.3% and 87% of the cases based on PR qualitative and quantitative evaluation, respectively, with no significant difference between the groups with respect to the baseline. The PR quantitative change in RD at the last recall session with respect to the baseline was not significant (all P values > .05) in both groups. The qualitative assessment of the type of REP root healing was nonuniform. In the test group, 55.6% of the teeth presented no RD and no apical closure. Only 50% of the 14 teeth assessed with CBCT imaging presented complete PBH. Regarding volumetric measurements on RD 3 years after REP for the change with respect to the baseline in root hard tissue volume, mean root hard tissue thickness, and apical area, the control group performed significantly in favor of RD than the test group (P = .03, .003, and 0.05 respectively). For the volumetric change 3 years after REP with respect to the baseline in root length and maximum root hard tissue thickness, no significant difference (P = .72 and .4, respectively) was found between the groups. The correlation between the PR and CBCT variables assessing RD was weak (root lengthening) to very weak (root thickening)., Conclusions: REP-LPRF seems to be a viable treatment option to obtain PBH and aid further RD of necrotic immature permanent teeth. Caution is needed when evaluating REP with PR., (Copyright © 2021 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)