Células tronco e endodontia regenerativa / Stem cells and regenerative endodontics

Desde o incremento das pesquisas das células-tronco em 1961, por cientistas canadenses, os avanços em estudos, pesquisas e o desenvolvimento de novos tratamentos com esse tipo de recurso se mostram promissores. O uso de células-tronco é uma grande aposta tanto para a medicina quanto para a odontologia regenerativa. Os tratamentos com essa terapia podem oferecer mais qualidade de vida para as pessoas. O potencial dessas células tão especiais se encontra em duas características peculiares: elas são capazes de se multiplicarem e de se diferenciarem em outros tipos de células, como de tecidos, cartilagens e neurônios. É dessa maneira que elas têm um papel fundamental para estudos e tratamentos relacionados à regeneração. O uso de células-tronco na Odontologia torna possível diferentes processos odontológicos que oferecem mais qualidade de vida ao paciente. Isso porque fatores como defeitos genéticos, hábitos nocivos, cáries dentárias e perdas precoces dos dentes contribuem com a perda de dentes ao longo da vida. No início do século XXI, por volta dos anos de 2005, 2006, pesquisadores começaram a publicar em revistas internacionais da área uma nova técnica baseada no uso de célulastronco existentes no osso de sustentação dos dentes e na articulação dento alveolar. Esta técnica, chamada de Revascularização, promove o aparecimento de um novo tecido pulpar sadio, devolvendo ao dente sua vitalidade e higidez(AU)

Since the increase in stem cell research in 1961 by Canadian scientists, advances in studies, research and the development of new treatments with this type of resource have shown promise. The use of stem cells is a big bet for both medicine and regenerative dentistry. Treatments with this therapy can offer more quality of life for people. The potential of these very special cells lies in two peculiar characteristics: they are able to multiply and differentiate into other types of cells, such as tissues, cartilage and neurons. It is in this way that they play a key role for studies and treatments related to regeneration. The use of stem cells in dentistry makes possible different dental processes that offer more quality of life to the patient. That's because factors such as genetic defects, harmful habits, tooth decay, and early tooth loss all contribute to lifelong tooth loss. At the beginning of the twenty-first century, around the years 2005, 2006, researchers began to publish in international journals of the area a new technique based on the use of existing stem cells in the supporting bone of the teeth and in the alveolar tooth joint. This technique, called Revascularization, promotes the appearance of a new healthy pulp tissue, returning to the tooth its vitality and hygiene(AU)

Temporal evolution of postsurgical bone repair in a rabbit model: A [99mTc]Tc-MDP scintigraphic study

Abstract Bone regeneration is crucial for repairing bone tissue following various injuries. Research techniques that enable the study of metabolic changes in bone tissue under different conditions are important for understanding bone repair and remodeling. This study used bone scintigraphy to evaluate osteogenesis secondary to osteotomy in a preclinical model of New Zealand rabbits. For this purpose, we conducted a longitudinal, prospective, case-control study in which scintigraphic variables were measured in both the right forearm (case-operated) and the left forearm (control - non-operated). The study sample consisted of 10 rabbits subjected to osteotomy, followed by a 12-week postoperative evaluation period, divided into six imaging stages at 1, 2, 3, 4, 8, and 12 weeks. We observed that the operated forearm showed significantly higher external radiation than the control side, using the pinhole collimator, denoting an increase in the biodistribution and tropism of the radiopharmaceutical to the operated forearm. Among the three evaluated time points, osteoblastic activity was highest in the second week and presented a significant decline in the 8th and 12th weeks, denoting regeneration and resolution of the surgical injury; the control forearm was also influenced by the inactivity imposed by the operated forearm. This fact was notably evidenced by the reduction in the metabolic activity of osteoblasts in the left forearm. Our study suggested that bone scintigraphy was sensitive enough to semi-quantitatively differentiate the metabolic activity of osteoblasts in the operated forearm in the three temporal landmarks evaluated in the study.

Demineralized freeze-dried bone allograft with/without i-Platelet-rich fibrin in 3 wall intrabony defects

Demineralized freeze-dried bone allograft (DFDBA) contains bone morphogenetic proteins (BMPs), hence is osteoinductive. Autologous platelet concentrates exhibit a higher quantity of growth factors. Both these biomaterials aid in bone regeneration when placed in three-wall intrabony defects. However, their efficacy when used alone and in conjugation is not clear. Aim: To assess clinical and radiographic efficacy of injectable platelet-rich fibrin (i-PRF) with microsurgical access flap in the treatment of three-wall intrabony defects in chronic periodontitis patients. Methods: Thirty sites with three-wall intrabony defects were randomly assigned to control and test group by computer generated method. The test group obtained i-PRF mixed with DFDBA while the control group received only DFDBA. Clinical parameters such as site-specific Plaque index (PI), Radiographic intrabony defect depth (IBDD), modified- Sulcular bleeding index (mSBI), Clinical attachment level (CAL), and Probing pocket depth (PPD) were measured at baseline, three and six months. Results: Intragroup comparison within the control group and test group exhibited statistically highly significant variation of mean PI, mSBI, PPD, CAL, and IBDD score from baseline to 3 months and from 3-6 months (p<0.001). However, intergroup comparison demonstrated no statistically significant variation of mean IBDD at all 3 intervals (p>0.05). Conclusion: i-PRF combined with DFDBA enhanced the radiographic and clinical parameters as opposed to DFDBA alone. The role of i-PRF is promising in its capacity for easy obtainability and increased potential to aid in regeneration

Clinical and radiographic evaluation of Bio-Oss granules and Bio-Oss Collagen in the treatment of periodontal intrabony defects: a retrospective cohort study

Abstract Objective This retrospective study aimed to analyze the clinical efficacy of two regenerative surgical methods — Bio-Oss granules combined with barrier membranes and Bio-Oss Collagen alone — and to help clinicians achieve better periodontal regeneration outcomes in the specific periodontal condition. Methodology Patients who underwent periodontal regeneration surgery from January 2018 to April 2022 were retrospectively screened, and their clinical and radiographic outcomes at 6 months postoperatively were analyzed. The probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), gingival recession (GR), distance from the cemento-enamel junction to the bottom of the bone defect (CEJ-BD), and depth of intrabony defects (INFRA) were recorded before the operation (T0) and 6 months after it (T1), and subsequently compared. Results In total, 143 patients were included — 77 were placed in the Bio-Oss group and 66 were placed in the Bio-Oss Collagen group. All indicators, including PD and CAL at T1, showed significant differences compared to baseline, for both groups (P<0.001). PD reduction was greater in the group receiving the Bio-Oss Collagen treatment (P=0.042). Furthermore, in cases when the baseline PD range was 7-11 mm and the age range was 35-50 years, PD reduction was more significant for patients receiving the Bio-Oss Collagen treatment (P=0.031, 0.023). A linear regression analysis indicated that postoperative PD and CAL were positively correlated with baseline values, and that the efficacy tended to decrease with increasing age. Conclusion Both the use of Bio-Oss Collagen alone and the use of Bio-Oss granules combined with barrier membranes resulted in significant effects in the treatment of periodontal intrabony defects. The Bio-Oss Collagen treatment generated more improvements in PD than the Bio-Oss granules combined with barrier membranes, particularly within the baseline PD range of 7-11 mm and the 35-50 years age group. Additionally, age was the main factor influencing the effectiveness of regenerative surgery for intrabony defects: older individuals exhibited fewer improvements.

Cobalt Chloride as a Hypoxia Mimicking Agent Induced HIF-1α and mTOR Expressions of Human Umbilical Cord Mesenchymal Stem Cells

ABSTRACT Objective: To assess the effects of cobalt chloride (CoCl2) as a hypoxia mimicking agent on human umbilical cord mesenchymal stem cells (hUCMSCs) expression of HIF-1α and mTOR for use in regenerative dentistry. Material and Methods: Human umbilical cord mesenchymal stem cells were isolated and then cultured. The characteristics of stemness were screened and confirmed by flow cytometry. The experiment was conducted on hypoxia (H) and normoxia (N) groups. Each group was divided and incubated into 24-, 48-, and 72-hours observations. Hypoxic treatment was performed using 100 µM CoCl2 on 5th passage cells in a conventional incubator (37°C; 5CO2). Then, immunofluorescence of HIF-1α and mTOR was done. Data was analyzed statistically using One-way ANOVA and Tukey's HSD. Results: Significant differences were found between normoxic and hypoxic groups on HIF-1α (p=0.015) and mTOR (p=0.000) expressions. The highest HIF-1α expression was found at 48 hours in the hypoxia group, while for mTOR at 24 hours in the hypoxia group. Conclusion: Hypoxia using cobalt chloride was able to increase human umbilical cord mesenchymal stem cells expression of HIF-1α and mTOR.

Endometrial mesenchymal stromal/stem cells improve regeneration of injured endometrium in mice

BACKGROUND: The monthly regeneration of human endometrial tissue is maintained by the presence of human endometrial mesenchymal stromal/stem cells (eMSC), a cell population co-expressing the perivascular markers CD140b and CD146. Endometrial regeneration is impaired in the presence of intrauterine adhesions, leading to infertility, recurrent pregnancy loss and placental abnormalities. Several types of somatic stem cells have been used to repair the damaged endometrium in animal models, reporting successful pregnancy. However, the ability of endometrial stem cells to repair the damaged endometrium remains unknown. METHODS: Electrocoagulation was applied to the left uterine horn of NOD/SCID mice causing endometrial injury. Human eMSC or PBS was then injected into the left injured horn while the right normal horn served as controls. Mice were sacrificed at different timepoints (Day 3, 7 and 14) and the endometrial morphological changes as well as the degree of endometrial injury and repair were observed by histological staining. Gene expression of various inflammatory markers was assessed using qPCR. The functionality of the repaired endometrium was evaluated by fertility test. RESULTS: Human eMSC successfully incorporated into the injured uterine horn, which displayed significant morphological restoration. Also, endometrium in the eMSC group showed better cell proliferation and glands formation than the PBS group. Although the number of blood vessels were similar between the two groups, gene expression of VEGF-α significantly increased in the eMSC group. Moreover, eMSC had a positive impact on the regeneration of both stromal and epithelial components of the mouse endometrium, indicated by significantly higher vimentin and CK19 protein expression. Reduced endometrial fibrosis and down-regulation of fibrosis markers were also observed in the eMSC group. The eMSC group had a significantly higher gene expression of anti-inflammatory factor Il-10 and lower mRNA level of pro-inflammatory factors Ifng and Il-2, indicating the role of eMSC in regulation of inflammatory reactions. The eMSC group showed higher implantation sites than the PBS group, suggesting better endometrial receptivity with the presence of newly emerged endometrial lining. CONCLUSIONS: Our findings suggest eMSC improves regeneration of injured endometrium in mice.

Research advances on stem cell-based treatments in animal studies and clinical trials of lymphedema / 中国修复重建外科杂志

OBJECTIVE@#To summarize the progress of the roles and mechanisms of various types of stem cell-based treatments and their combination therapies in both animal studies and clinical trials of lymphedema.@*METHODS@#The literature on stem cell-based treatments for lymphedema in recent years at home and abroad was extensively reviewed, and the animal studies and clinical trials on different types of stem cells for lymphedema were summarized.@*RESULTS@#Various types of stem cells have shown certain effects in animal studies and clinical trials on the treatment of lymphedema, mainly through local differentiation into lymphoid endothelial cells and paracrine cytokines with different functions. Current research focuses on two cell types, adipose derived stem cells and bone marrow mesenchymal stem cells, both of which have their own advantages and disadvantages, mainly reflected in the therapeutic effect of stem cells, the difficulty of obtaining stem cells and the content in vivo. In addition, stem cells can also play a synergistic role in combination with other treatments, such as conservative treatment, surgical intervention, cytokines, biological scaffolds, and so on. However, it is still limited to the basic research stage, and only a small number of studies have completed clinical trials.@*CONCLUSION@#Stem cells have great transformation potential in the treatment of lymphedema, but there is no unified standard in the selection of cell types, the amount of transplanted cells, and the timing of transplantation.

Reconstruction of rat calvarial defects utilizing an ultraviolet-cured hydrogel loaded with bone marrow mesenchymal stem cells / 口腔疾病防治

Objective@#To investigate the osteogenic properties of a methacrylated gelatin (GelMA) / bone marrow mesenchymal stem cells (BMSCs) composite hydrogel applied to the skull defect area of rats and to provide an experimental basis for the development of bone regeneration biomaterials.@*Methods@#This study was approved by the Animal Ethics Committee of Nanjing University. A novel photocurable composite biohydrogel was developed by constructing photoinitiators [lthium phenyl (2,4,6-trimethylbenzoyl) phosphinate, LAP], GelMA, and BMSCs. The surface morphology and elemental composition of the gel were examined using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). The compressive strength of the gel was evaluated using an electronic universal testing machine. After in vitro culture for 1, 2, and 5 days, the proliferation of the BMSCs in the hydrogels was assessed using a CCK-8 assay, and their survival and morphology were examined through confocal microscopy. A 5 mm critical bone deficiency model was generated in a rat skull. The group receiving composite hydrogel treatment was referred to as the GelMA/BMSCs group, whereas the untreated group served as the control group. At the 4th and 8th weeks, micro-CT scans were taken to measure the bone defect area and new bone index, while at the 8th week, skull samples from the defect area were subjected to H&E staining, van Gieson staining, and Goldner staining to evaluate the quality of bone regeneration and new bone formation.@*Results@#SEM observed that the solidified GelMA showed a 3D spongy gel network with uniform morphology, the porosity of GelMA was 73.41% and the pore size of GelMA was (28.75 ± 7.13) μm. EDX results showed that C and O were evenly distributed in the network macroporous structure of hydrogel. The hydrogel compression strength was 152 kPa. On the 5th day of GelMA/BMSCs culture, the cellular morphology transitioned from oval to spindle shaped under microscopic observation, accompanied by a significant increase in cell proliferation (159.4%, as determined by the CCK-8 assay). At 4 weeks after surgery, a 3D reconstructed micro-CT image revealed a minimal reduction in bone defect size within the control group and abundant new bone formation in the GelMA/BMSCs group. At 8 weeks after surgery, no significant changes were observed in the control group's bone defect area, with only limited evidence of new bone growth; however, substantial healing of skull defects was evident in the GelMA/BMSCs group. Quantitative analysis at both the 4- and 8-week examinations indicated significant improvements in the new bone volume (BV), new bone volume/total bone volume (BV/TV), bone surface (BS), and bone surface/total bone volume (BS/TV) in the GelMA/BMSCs group compared to those in the control group (P<0.05). Histological staining showed continuous and dense formation of bone tissue within the defects in the GelMA/BMSCs group and only sporadic formation of new bone, primarily consisting of fibrous connective tissue, at the defect edge in the control group.@*Conclusion@#Photocuring hydrogel-based stem cell therapy exhibits favorable biosafety profiles and has potential for clinical application by inducing new bone formation and promoting maturation within rat skull defects.

Effect of Fuzheng Huayu prescription on hepatocyte extinction and regeneration in a mouse model of liver cirrhosis / 临床肝胆病杂志

ObjectiveTo investigate the effect of Fuzheng Huayu prescription on hepatocyte extinction and regeneration in fibrotic liver and its mechanism of action in promoting hepatocyte regeneration. MethodsMice were given intraperitoneal injection of CCl4 for 6 weeks to establish a model of liver cirrhosis， and there were 10 mice in the model group， 10 in the sorafenib group， 10 in the Fuzheng Huayu prescription group， and 9 in the normal control group. Since week 4 of modeling， the mice in the Fuzheng Huayu prescription group and the sorafenib group were given the corresponding drug by gavage at a dose of 4.8 g/kg and 4 mg/kg， respectively， for three consecutive weeks， and those in the normal group and the model group were given an equal volume of sodium carboxymethyl cellulose. Serum liver function parameters were measured； the METAVIR scoring system was used to evaluate liver inflammation and fibrosis stage； Sirius Red staining and hydroxyproline （Hyp） content in liver tissue were used to evaluate collagen deposition； immunohistochemistry was used to measure the protein expression levels of type IV collagen， CD31， CD32b， Ki67， CyclinD1， glutamine synthetase， Wnt2， and HGF， and Western blot was used to measure the expression levels of Wnt2， LRP6， β-catenin， p-β-catenin， and CyclinD1 in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group， the Fuzheng Huayu prescription group and the sorafenib group showed the following changes： significant reductions in the serum levels of alanine aminotransferase and aspartate aminotransferase and the content of Hyp in liver tissue （all P<0.01）； a significant reduction in METAVIR score； significant reductions in the expression levels of type Ⅳ collagen and CD31 （all P<0.05） and a significant increase in the expression level of CD32b （P<0.01）； significant reductions in the number of parenchymal extinction lesions and significant increases in the expression levels of Ki67 and CyclinD1 in liver tissue （all P<0.01）； significant increases in the protein expression levels of Wnt2， LRP6， β-catenin， and CyclinD1 and a significant reduction in the protein expression level of p-β-catenin （all P<0.05）； significant increases in the number of cells stained positive for both CD32b and Wnt2. ConclusionFuzheng Huayu prescription can inhibit hepatic sinusoidal capillarization， improve the Wnt2 exocrine function of liver sinusoidal endothelial cells， activate the Wnt/β-catenin signaling pathway associated with hepatocyte regeneration， and finally reverse liver cirrhosis.

3D printed Mg-incorporated polycaprolactone scaffolds for repairing rat skull defects / 口腔疾病防治

Objective@#To evaluate the bone repair effect of 3D-printed magnesium (Mg)-loaded polycaprolactone (PCL) scaffolds in a rat skull defect model.@*Methods@#PCL scaffolds mixed with Mg microparticles were prepared by using 3D printing technology, as were pure PCL scaffolds. The surface morphologies of the two scaffolds were observed by scanning electron microscopy (SEM), and the surface elemental composition was analyzed via energy dispersive spectroscopy (EDS). The physical properties of the scaffolds were characterized through contact angle measurements and an electronic universal testing machine. This study has been reviewed and approved by the Ethics Committee. A critical size defect model was established in the skull of 15 Sprague-Dawley (SD) rats, which were divided into the PCL group, PCL-Mg group, and untreated group, with 5 rats in each group. Micro-CT scanning was performed to detect and analyze skull defect healing at 4 and 8 weeks after surgery, and samples from the skull defect area and major organs of the rats were obtained for histological staining at 8 weeks after surgery.@*Results@#The scaffolds had a pore size of (480 ± 25) μm, a fiber diameter of (300 ± 25) μm, and a porosity of approximately 66%. The PCL-Mg scaffolds contained 1.0 At% Mg, indicating successful incorporation of Mg microparticles. The contact angle of the PCL-Mg scaffolds was 68.97° ± 1.39°, indicating improved wettability compared to that of pure PCL scaffolds. Additionally, compared with that of pure PCL scaffolds, the compressive modulus of the PCL-Mg scaffolds was (57.37 ± 8.33) MPa, demonstrating enhanced strength. The PCL-Mg group exhibited the best bone formation behavior in the skull defect area compared with the control group and PCL group at 4 and 8 weeks after surgery. Moreover, quantitative parameters, such as bone volume (BV), bone volume/total volume (BV/TV), bone surface (BS), bone surface/total volume (BS/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N) and bone mineral density (BMD), of skull defects were better than those in the other groups, indicating the best bone regeneration effect. H&E, Goldner, and VG staining revealed more mineralized new bone formation in the PCL-Mg group than in the other groups, and H&E staining of the major organs revealed good biosafety of the material.@*Conclusion@#PCL-Mg scaffolds can promote the repair of bone defects and have clinical potential as a new scaffold material for the repair of maxillofacial bone defects.

Phosphatidic acid-enabled MKL1 contributes to liver regeneration: Translational implication in liver failure

Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner

Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.

Stem Cell-Based Hair Cell Regeneration and Therapy in the Inner Ear / 神经科学通报·英文版

Hearing loss has become increasingly prevalent and causes considerable disability, thus gravely burdening the global economy. Irreversible loss of hair cells is a main cause of sensorineural hearing loss, and currently, the only relatively effective clinical treatments are limited to digital hearing equipment like cochlear implants and hearing aids, but these are of limited benefit in patients. It is therefore urgent to understand the mechanisms of damage repair in order to develop new neuroprotective strategies. At present, how to promote the regeneration of functional hair cells is a key scientific question in the field of hearing research. Multiple signaling pathways and transcriptional factors trigger the activation of hair cell progenitors and ensure the maturation of newborn hair cells, and in this article, we first review the principal mechanisms underlying hair cell reproduction. We then further discuss therapeutic strategies involving the co-regulation of multiple signaling pathways in order to induce effective functional hair cell regeneration after degeneration, and we summarize current achievements in hair cell regeneration. Lastly, we discuss potential future approaches, such as small molecule drugs and gene therapy, which might be applied for regenerating functional hair cells in the clinic.

Bioceramic scaffolds with two-step internal/external modification of copper-containing polydopamine enhance antibacterial and alveolar bone regeneration capability / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Magnesium-doped calcium silicate (CS) bioceramic scaffolds have unique advantages in mandibular defect repair; however, they lack antibacterial properties to cope with the complex oral microbiome. Herein, for the first time, the CS scaffold was functionally modified with a novel copper-containing polydopamine (PDA(Cu2+‍)) rapid deposition method, to construct internally modified (*P), externally modified (@PDA), and dually modified (*P@PDA) scaffolds. The morphology, degradation behavior, and mechanical properties of the obtained scaffolds were evaluated in vitro. The results showed that the CS*P@PDA had a unique micro-/nano-structural surface and appreciable mechanical resistance. During the prolonged immersion stage, the release of copper ions from the CS*P@PDA scaffolds was rapid in the early stage and exhibited long-term sustained release. The in vitro evaluation revealed that the release behavior of copper ions ascribed an excellent antibacterial effect to the CS*P@PDA, while the scaffolds retained good cytocompatibility with improved osteogenesis and angiogenesis effects. Finally, the PDA(Cu2+)-modified scaffolds showed effective early bone regeneration in a critical-size rabbit mandibular defect model. Overall, it was indicated that considerable antibacterial property along with the enhancement of alveolar bone regeneration can be imparted to the scaffold by the two-step PDA(Cu2+) modification, and the convenience and wide applicability of this technique make it a promising strategy to avoid bacterial infections on implants.

Research progress on dedifferentiated fat cells and their application in oral and maxillofacial bone tissue engineering / 口腔疾病防治

@#The identification of suitable seed cells represents a critical scientific problem to be solved in the field of oral and maxillofacial bone tissue regeneration. The application of adipose-derived stem cells (ASCs) in tissue and organ repair and regeneration has been studied extensively. In recent years, dedifferentiated fat (DFAT) cells have also shown broad application prospects in the field of bone tissue engineering. DFAT cells express stem cell-related markers and have the potential to differentiate into adipocytes, osteoblasts, chondrocytes, nerve cells, cardiomyocytes and endothelial cells. In addition, DFAT cells also have the advantages of minimally invasive acquisition, strong proliferation and high homogeneity. Currently, all studies involving the application of DFAT cells in scaffold-based and scaffold-free bone tissue engineering can confirm their effectiveness in promoting bone regeneration. However, cytological research still faces some challenges, including relatively low cell culture purity, unclear phenotypic characteristics and undefined dedifferentiation mechanisms. It is believed that with the continuous development and improvement of isolation, culture, identification and directional induction of osteogenic differentiation methods, DFAT cells are expected to become excellent seed cells in the field of oral and maxillofacial bone tissue engineering in the future.

Research progress on cemental tears in terms of clinical diagnosis and treatment / 口腔疾病防治

@#A cemental tear is defined as an incomplete or complete detachment of the cementum along the dentino-cemental junction (CDJ) or the incremental line within the body of the cementum, which can also involve part of the root dentine adjacent to the cementum. The pathogenesis of cemental tears is not fully elucidated. From the literature review, possible predisposing factors were identified, including tooth type, sex, age, periodontitis, previous periodontal treatment or root canal treatment, history of dental trauma, and occlusal trauma or excessive occlusal force. The morphology of cemental tears can be either piece-shaped or U-shaped, which usually contributes to periodontal and periapical breakdown. Clinically, cemental tears have a unitary periodontal pocket and present with symptoms mimicking localized periodontitis, apical periodontitis, and vertical root fractures. Imaging examination is of great significance for the clinical diagnosis of cemental tears, which often manifest as thin ‘prickle-like’ radiopaque masses located longitudinally adjacent to the affected root surface. Exploratory surgery is needed in some cases. Although intraoperative cemental fragments and cemental lines on the root surface can assist in the diagnostic process, histopathology examination is the gold standard for the diagnosis of cemental tears. The treatment methods vary depending on the timing of the correct diagnosis and the clinical or radiological manifestations. With the development of regenerative biomaterials and the development of intentional replantation, an increasing number of affected teeth can survive for a long time. The aim of this review is to systematically describe the biological basis and predisposing factors, clinical features, radiographic and histological characteristics, diagnosis and clinical management of cemental tears, and treatment outcomes to help make a clear diagnosis and develop a personalized treatment plan.

The applications of the plasma matrix in the treatments of dental pulp and periapical diseases / 口腔疾病防治

@#The plasma matrix is a kind of autologous blood conduct. It has been widely used in maxillofacial tissue regeneration, skin cosmetology and some other fields. Recently, to preserve the dental pulp as well as the teeth, pulp regeneration therapy and apical surgery have become increasingly important as well as the applications of bioactive materials. As a kind of autologous bioactive material, the plasma matrix has some natural advantages as it is easy to obtain and malleable. The plasma matrix can be used in the following cases: ①pulp revascularization of young permanent teeth with open apical foramina that cannot stimulate apical bleeding; ② apical barrier surgery with bone defects and large area perforation repair with bone defects or root sidewall repair surgery; ③ apical surgeries of teeth with large area of apical lesions, with or without periodontal diseases. The plasma matrix is a product derived from our blood, and there are no obvious contraindications for its use. Several systematic reviews have shown that the plasma matrix can effectively promote the regenerative repair of dental pulp in patients with periapical diseases. However, the applications of plasma matrix are different because its characteristics are affected by different preparation methods. In addition, there is still a lack of long-term clinical researches on the plasma matrix, and the histological evidences are difficult to obtain, so a large number of in vitro and in vivo experimental studies are still needed. This article will describe the applications of different kinds of plasma matrix for dental pulp regeneration and bone tissue regeneration in apical surgeries to provide references for clinicians in indication selection and prognosis evaluation.

Research progress on immunomodulatory properties of periodontal ligament stem cells / 口腔疾病防治

@#Periodontal ligament stem cells (PDLSCs) have the potential for multidirectional differentiation and are the preferred seed cells for periodontal tissue regeneration. In recent years, a large number of studies have confirmed that PDLSCs also possess broad immunomodulatory properties. Therefore, in-depth exploration of their specific molecular mechanisms is of great significance for the treatment of periodontitis. The aim of this paper is to summarize the research progress on the regulation of PDLSCs on various immune cells and the effect of the inflammatory environment on the immune characteristics of PDLSCs to provide an important theoretical basis for the allotransplantation of PDLSCs and improve the therapeutic effect of periodontal tissue regeneration. Studies have shown that PDLSCs possess a certain degree of immunosuppressive effect on both innate and acquired immune cells, and inflammatory stimulation may lead to the impairment of the immunoregulatory properties of PDLSCs. However, current studies are mainly limited to in vitro cell tests and lack in-depth studies on the immunomodulatory effects of PDLSCs in vivo. In vivo studies based on cell lineage tracing and conditional gene knockout technology may become the main directions for future research.

Uso de L-PRF en defectos infraóseos de pacientes con estadios avanzados de periodontitis / Use of L-PRF in intrabone defects in patients with advanced stages of periodontitis

Objetivo: El propósito de este estudio fue observar el efecto del uso de L-PRF en defectos infraoseos de pacientes con periodontitis en estadios avanzados. Métodos: Se incluyeron 32 defectos infraoseos de 12 pacientes con diagnóstico de Periodontitis estadio III y IV (Workshop 2018). Se realizó raspaje a campo abierto con colocación de membrana de L-PRF. Se incluyeron defectos infraóseos de 1-2-3 paredes y cráter óseo. Se registró la profundidad de sondaje (PS), nivel de inserción clínica (NIC), índice de placa (IP) e índice de sangrado (IS). Se realizaron radiografías periapicale digitales antes de la cirugía y al cuarto mes para observar el llenado óseo. Resultados: De los 32 defectos el 75 % mostró disminución de la profundidad de sondaje (PS) y el 66 % mejoro el nivel de inserción clínica (NIC). Se realizó un análisis de correlación pre y posquirúrgico en PS: MV (p = 0,02), MP/L (p = 0,00), DP/L (p = 0,00) y V (p =0,00). El porcentaje de llenado óseo fue de 62,96 % (DS± 3,88). Conclusiones: La mayoría de los defectos infraóseos mostraron radiográficamente llenado óseo parcial o total con el uso de membranas L-PRF. Además, se mejoraron los parámetros clínicos de profundidad de sondaje y nivel de inserción clínica.

Objective: The purpose of this study was to observe the effect of L-PRF (Leuko- cyte-Platelet Rich Fibrin) usage in intraosseous defects in patients with advanced-stages of periodontitis. Methods: Thirty-two intraosseous defects in 12 patients diagnosed with stage III and IV periodontitis (Workshop 2018) were included in the study. Open flap debridement was performed with the placement of L-PRF membranes. Included defects consisted of 1-2-3 wall defects and osseous craters. Parameters such as probing depth (PD), clinical attachment level (CAL), plaque index (PI), and bleeding index (BI) were recorded. Digital periapical radiographs were taken before surgery and at the fourth month to assess bone fill. Results: Out of the 32 defects, 75% showed a reduction in probing depth (PD), and 66% showed improvement in clinical attachment level (CAL). Pre- and post-surgical correlation analysis was performed for PD: MV (p = 0.02), PI/L (p = 0.00), BI/L (p = 0.00), and CAL (p = 0.00). The percentage of bone fill was 62.96% (±3.88 SD). Conclusion: The majority of intraosseous defects exhibited partial or complete radiographic bone fill with the use of L-PRF membranes. Furthermore, clinical parameters such as probing depth and clinical attachment level improved.

Preservação óssea alveolar pós exodontia: objetivos, opções técnicas, vantagens e desvantagens / Alveolar bone preservation after tooth extraction: objectives, technical options, advantages and disadvantages

A extração do elemento dentário promove uma série de eventos biológicos que resultam no colapso da estrutura alveolar, ocasionando a perda óssea volumétrica na região de extração. Preservar esse alvéolo dentário é imprescindível para uma boa reabilitação dentária do paciente. Objetivo: Realizar uma revisão de literatura abordando os objetivos, opções técnicas, vantagens e desvantagens da preservação óssea alveolar pós extração. Materiais e métodos: Foi feita uma revisão de literatura utilizando as bases de dados Biblioteca Virtual em Saúde (BVS), PubMed e Google acadêmico, usando os descritores "extração dentária", "perda do osso alveolar", "regeneração óssea". Foram incluídos 34 artigos. Resultados: A preservação alveolar pós extração começa desde a realização de uma técnica cirúrgica menos invasiva até a colocação de enxertos do tipo autógenos, alógenos, xenógenos, aloplásticos e biomateriais promotores de cicatrização e reparação tecidual. Conclusão: Existe na literatura atual uma vasta gama de textos científicos que abordam técnicas de preservação alveolar pós exodontia, com distintas respostas teciduais. Todavia, nenhum biomaterial listado nesta revisão contém todas as características que proporcionam regeneração completa do osso alveolar após exodontia(AU)

The extraction of the dental element promotes a series of biological events that results in the collapse of the alveolar structure, causing volumetric bone loss in the region of extraction. Preserving this dental alveolus is essential for a good dental rehabilitation of the patient. Objective: To conduct a literature review addressing the objectives, technical options, advantages and disadvantages of post-extraction alveolar bone preservation. Materials and methods: A literature review was carried out using the Virtual Health Library (VHL), PubMed and academic Google databases, using the descriptors "tooth extraction", "alveolar bone loss", "bone regeneration". 34 articles were included. Results: Post-extraction alveolar preservation starts from the performance of a less invasive surgical technique to the placement of autogenous, allogeneic, xenogeneic, alloplastic and biomaterials that promote healing and tissue repair. Conclusion: There´s is a wide range of scientific texts in the current literature that address post-extraction alveolar preservation techniques with different tissue responses. However, none of the biomaterials listed in this review contain all the characteristics that provide complete regeneration of alveolar bone after extraction(AU)