Impact of Collared Peccaries Dycotiles tajacu (Artiodactyla: Tayassuidae) on understory vegetation in the tropical rainforest of the Nogal-La Selva Biological Corridor, Costa Rica / Impacto del pecarí de collar, Dycotiles tajacu (Artiodactyla: Tayassuidae) en la vegetación del sotobosque del bosque tropical húmedo del Corredor Biológico Local Nogal-La Selva, Costa Rica

Abstract Introduction: Evidence suggests that herbivores, such as peccaries, shape vegetation structure and diversity through predation, trampling, dispersal, and rooting behavior. Objective: To evaluate the impact of peccaries (Dycotiles tajacu) on the understory vegetation of the tropical rainforest in the Nogal-La Selva Local Biological Corridor, Costa Rica, comparing a site with the absence of peccaries to another with the presence of these animals. Methodology: From June to November 2021, 20 experimental exclusions and 20 free access plots, each measuring 2 m2 were used to quantify herbivory, the number of leaf blades, damaged leaves, healthy leaves, sapling height, and fallen biomass at both sites. Results: A higher sapling density was found in the Nogal Reserve, but a lower sapling diversity, while in La Selva there was a higher sapling diversity, but a lower density of seedlings. Herbivory and sapling height in La Selva exceeded those in Nogal. The exclusion of peccaries reduced seedling damage but did not affect the dynamics of fallen biomass. Conclusion: For the design, implementation, and evaluation of the effectiveness of biological corridors, it is crucial to consider plant-animal interactions to enhance the flow of ecological processes through functional and structural connectivity, analyzed from interactions such as those presented in this paper.

Resumen Introducción: Existe evidencia que herbívoros, como los saínos, dan forma a la estructura y diversidad de la vegetación a través del comportamiento de depredación, pisoteo, dispersión y enraizamiento. Objetivo: Evaluar el impacto de los saínos (Dycotiles tajacu) en la vegetación del sotobosque del bosque tropical húmedo en el Corredor Biológico Local Nogal-La Selva, Costa Rica, en un sitio con ausencia y en otro con presencia de saínos. Métodos: De junio a noviembre de 2021 se utilizaron 20 exclusiones experimentales y 20 parcelas de acceso libre de 2 m2, se cuantifico la herbivoría, número de láminas foliares, hojas dañadas, hojas sanas, altura de brinzales y biomasa caída en ambos sitios. Resultados: Se encontró una mayor densidad de brinzales en Reserva Nogal pero una menor diversidad, contrario en La Selva donde se encontró una mayor diversidad de brinzales, pero una menor densidad de plántulas. La herbivoría y la altura de brinzales en La Selva fue mayor que en Nogal. La exclusión de los saínos disminuyó el daño a las plántulas, pero no afectó la dinámica de la biomasa caída. Conclusión: Es necesario contemplar para el diseño, implementación y evaluación de la efectividad de corredores biológicos, las interacciones planta-animal, para potencializar el flujo de procesos ecológicos mediante la conectividad funcional y estructural, analizada a partir de interacciones como las presentadas en este trabajo.

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)

Injertos Óseos en Quistes de los Maxilares. Reporte de un Caso

Los quistes de los maxilares son las lesiones óseas más comunes en la región maxilofacial. La enucleación de las lesiones y el cierre primario de los defectos, son en conjunto, el tratamiento óptimo hoy en día. En algunas ocasiones el defecto óseo resultante puede ser de un tamaño tan grande que afecta la estabilidad de dientes vecinos, comprometa la indemnidad del hueso o produce un retraso cicatrizal que incluso puede impedir una regeneración ósea completa. Se considera que esta falta de regeneración expone al paciente a riesgos de infección tardía, retraso de los tratamientos rehabilitadores en zonas de alta demanda estética y pérdida de vitalidad dentaria. Para disminuir el riesgo de alteraciones en la regeneración ósea completa de cavidades quísticas, se ha propuesto la posibilidad de que tras la enucleación del quiste se rellenen estos defectos con injertos óseos u otras técnicas de preservación alveolar para favorecer la cicatrización. Teóricamente el uso de estos injertos mejora la calidad y disminuye el tiempo de cicatrización ósea, permitiendo que el paciente recupere rápidamente las funciones habituales del componente dentoalveolar, acortando el periodo de cuidados postoperatorios que restringen la alimentación, los deportes o la rehabilitación oral. El actual trabajo tiene como objetivo realizar una revisión de la literatura respecto a los beneficios del uso de injertos óseos en el tratamiento quirúrgico de los quistes maxilares y presentar un caso clínico con los detalles quirúrgicos de esta técnica.

Jaw cysts are the most common bone lesions in the maxillofacial region. Enucleation of the lesions along with the primary closure of the defects are the optimal treatment nowadays. On some occasions, the resulting bone defect can be so large that it affects the stability of neighboring teeth, compromises the integrity of the bone, or produces a delayed healing that can even prevent complete bone regeneration. It is considered that the lack of regeneration exposes the patient to risk of infection, delay of rehabilitation treatments in areas of high aesthetic demand and loss of dental vitality. To reduce the risk of alterations in complete bone regeneration of cystic cavities, the possibility of filling these defects with bone grafts or other alveolar preservation techniques to promote healing, has been proposed after cyst enucleation. Theoretically, the use of these grafts improves the quality and decreases the bone healing time, allowing the patient to quickly recover the usual functions of the dentoalveolar component, limiting the period of postoperative care that restricts eating, sports or oral rehabilitation. The present work aims to carry out a review of the literature regarding the benefits of the use of bone grafts in the surgical treatment of maxillary cysts and to present a clinical case with the surgical details of this technique.

Fibrina rica en plaquetas como parte de la regeneración tisular en procedimientos quirúrgicos odontológicos / Platelet-rich fibrin as part of tissue regeneration in dental surgical procedures

Uno de los mejores biomateriales usados en odontología es la fibrina rica en plaquetas (PRF), es un concentrado plaquetario de segunda generación que se obtiene a partir de la centrifugación de sangre autóloga y no necesita aditivos. El presente documento busca determinar la eficacia del uso del PRF como parte de la regeneración de tejidos en procedimientos quirúrgicos odontológicos, tomando como base la literatura publicada en PubMed, Elsevier y Semantic Scholar entre 2018 y 2023, la búsqueda de artículos científicos fue ejecutada empleando las palabras clave platalet rich fibrin, regeneration, dentistry, blood buffy coat. La evidencia científica muestra que el PRF puede ser usado en su forma de membrana, gel, tapón, solo o combinado con otro biomaterial para conseguir propiedades biológicas exclusivas que promueven la regeneración y cicatrización mientras reduce los efectos adversos de los procedimientos quirúrgicos. Un ensayo clínico refirió la curación de alvéolos post exodoncia atraumática, y comprobó que la cicatrización con PRF muestra un índice de curación más alto en comparación con el grupo control. El sustento biológico de su eficacia radica en su capacidad para proliferar células que promueven la angiogénesis, osteogénesis y diferenciación celular, es decir, el reparo de tejidos lesionados. Todo esto nos permite llegar a la conclusión de que el PRF representa una alternativa viable y eficaz en procesos de regeneración de tejidos en procedimientos quirúrgicos odontológicos.

One of the best biomaterials used in dentistry is platelet-rich fibrin (PRF). It is a second-generation platelet concentrate obtained by centrifugation of autologous blood and requires no additives. The aim of this article is to determine the effectiveness of using PRF for tissue regeneration in dental surgery. The methodology used consists of a descriptive search of scientific articles that employ or study PRF as a biomaterial for tissue healing in the dental field and are available on PubMed, Elsevier, and Semantic Scholar. The literature shows that PRF can be used as a membrane, gel, cap form, alone or combined with other biomaterials to achieve unique biological properties that promote regeneration and healing while reducing the adverse effects of surgical procedures. For example, a clinical trial demonstrated healing of post-traumatic alveolar exodontia, proving that healing with PRF had a higher healing rate than in the control group. The biological basis of PRF's efficacy lies in its ability to proliferate cells that promote angiogenesis, osteogenesis, and cellular differentiation, and thus repair damaged tissue. All this leads us to conclude that PRF represents a viable and effective alternative in tissue regeneration processes in dental surgery procedures.

Fibroma ameloblástico mandibular: caso clínico / Fibroblastic fibroma mandibular: a clinical case

El fibroma ameloblástico (FA) se describe como una neoplasia benigna de origen odontogénico mixto que suele presentarse entre la primera y segunda década de vida, frecuentemente en los molares permanentes inferiores. Por lo general es asintomático, pero las lesiones de gran tamaño suelen acompañarse con dolor e inflamación. Su tratamiento por lo regular es conservador. Se describe el caso de un fibroma ameloblástico en un paciente de 13 años de edad, que involucraba cuerpo y ángulo mandibular izquierdo, tratado de manera conservadora, se realiza extirpación del tumor, regeneración ósea guiada y rehabilitación con implante dental (AU)

Ameloblastic fibroma (AF) is described as a benign neoplasm of mixed odontogenic origin that usually presents between the first and second decade of life, frequently in lower permanent molars. It is usually asymptomatic, but large lesions are usually accompanied by pain and inflammation. His treatment is generally conservative. The clinical case of an ameloblastic fibroma in a 13-year-old patient is described, involving the left mandibular body and angle, treated conservatively, tumor removal, guided bone regeneration and rehabilitation with dental implants are performed (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.

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.

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.

Validação biológica de grânulos de vidro bioativas (compostos por biovidro 45S5): estudo in vitro e in vivo / Biological validation of bioactive glass granules (composed of 45S5 bioglass): in vitro and in vivo study

O tecido ósseo, embora tenha a capacidade de regeneração, é limitado em sua eficácia diante de defeitos críticos que impedem a regeneração natural. Dessa forma, materiais como a hidroxiapatita (HA) têm sido considerados promissores na engenharia de tecido ósseo. Contudo, apesar de sua ampla utilização, a hidroxiapatita apresenta desvantagens, como a taxa de reabsorção e remodelação lenta. Em contraste, o biovidro 45S5 se destaca por sua biocompatibilidade, propriedades bioativas e degradabilidade. Este estudo objetivou avaliar o comportamento biológico in vitro e in vivo de grânulos de vidro bioativas de biovidro 45S5 fabricadas pelo método de fusão. Os biovidros foram caracterizados por meio da difração de raios X (DRX), espectroscopia de infravermelho por transformação de Fourier (FTIR), calorimetria diferencial de varredura (DSC) e espectrometria de emissão óptica com plasmas indutivamente acoplados (ICP OES). Em seguida, foi realizado o estudo in vitro, utilizando células osteoblásticas isoladas de fêmures de ratos, que foram submetidas a análise da morfologia celular (MEV), viabilidade celular (MTT), conteúdo de proteína total (PT), atividade de fosfatase alcalina (ALP) e formação de nódulos de mineralização. No estudo in vivo, foram realizados defeitos ósseos críticos de 7 mm na tíbia de coelhos da raça New Zealand, que foram divididos em dois grupos (n=6) de acordo com o material de preenchimento: hidroxiapatita comercial (HA) e biovidro 45S5 (BG45S5). Após 2, 8 e 12 semanas, os animais foram eutanasiados e as peças ósseas foram submetidas as análises histológicas e histomorfométricas. Os dados foram submetidos ao teste de normalidade Shapiro-Wilk (p=0,05) e quando normais realizamos o teste t de student e quando não normais realizamos o teste de Mann-Whitney. Os resultados dos testes físico-químicos mostraram sucesso na produção do novo biomaterial. Nos testes in vitro, observou-se que o grupo BG45S5 não apresentou citotoxicidade e mostrou-se promissor com diferença estatisticamente significante em relação ao grupo hidroxiapatita comercial (p=0.0263). Nos testes de PT, ALP e nódulos de mineralização, os grupos não apresentaram diferença estatística entre eles (p<0,05). Contudo, o grupo BG45S5 mostrou-se promissor em relação aos outros grupos. Na análise histológica, ambos os grupos apresentaram neoformação óssea nos defeitos após 2, 8 e 12 semanas. Na histomorfometria, observou-se que os grupos BG45S5 e HA apresentaram maior área de neoformação óssea em 12 semanas. Houve diferença estatisticamente significante entre os grupos no tempo de 2 semanas, com maior neoformação para o grupo BG45S5. Apesar dos resultados promissores do grupo BG45S5, não houve diferença estatisticamente significativa entre os grupos (p<0,05) nos tempos de 8 e 12 semanas. Em resumo, os resultados evidenciaram o sucesso na produção do biomaterial sintético e o potencial do biomaterial BG45S5 como um material promissor para tratamento de defeitos ósseos críticos. (AU)

Bone tissue, despite its capacity of regeneration, is limited in its effectiveness when faced with critical defects that prevent natural regeneration. Therefore, materials such as hydroxyapatite (HA) have been considered promising in bone tissue engineering. However, despite its wide use, hydroxyapatite has disadvantages, such as slow resorption and remodeling rates. In contrast, 45S5 bioglass stands out for its biocompatibility, bioactive properties and degradability. This study aimed to evaluate the in vitro and in vivo biological behavior of bioactive 45S5 bioglass beads manufactured by the melt quenched method. The bioglasses were characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and inductively coupled plasma optical emission spectrometry (ICP OES). Following this, an in vitro study was conducted using osteoblastic cells isolated from rat femurs, which were subjected to analysis of cell morphology (SEM), cell viability (MTT), total protein content (TP), alkaline phosphatase activity (ALP) and mineralization nodule formation. In the in vivo study, critical bone defects of 7 mm were created in the tibia of New Zealand rabbits, which were divided into two groups (n=6) according to the filling material: commercial hydroxyapatite (HA) and bioactive glass 45S5 (BG45S5). After 2, 8, and 12 weeks, the animals were euthanized and the bone pieces were subjected to histological and histomorphometric analyses. Data were subjected to the Shapiro-Wilk normality test (p=0.05), and when normal, we performed the Student's t-test, and when non-normal, we performed the Mann-Whitney test. The results of the physicochemical tests showed success in the production of the new biomaterial. In the in vitro tests, it was observed that the BG45S5 group did not present cytotoxicity and showed promise with a statistically significant difference compared to the commercial hydroxyapatite group (p=0.0263). In the TP, ALP and mineralization nodule tests, the groups showed no statistical difference between them (p<0.05). However, the BG45S5 group showed promise compared to the other groups. In the histological analysis, both groups showed new bone formation in the defects after 2, 8, and 12 weeks. In the histomorphometric analysis, it was observed that the BG45S5 and HA groups presented a larger area of new bone formation at 12 weeks. There was a statistically significant difference between the groups at 2 weeks, with greater new formation for the BG45S5 group. Despite the promising results of the BG45S5 group, there was no statistically significant difference between the groups (p<0.05) at 8 and 12 weeks. In summary, the results evidenced the successful production of the synthetic biomaterial and the potential of the BG45S5 bioglass as a promising material for treating critical bone defect.(AU)

Long-term outcomes of modified transcanalicular diode laser dacryocystorhinostomy

ABSTRACT Purpose: The purpose of this study is to assess the long-term outcomes of modified transcanalicular diode laser dacryocystorhinostomy in a large cohort of patients affected by primary acquired nasolacrimal duct obstruction. Methods: This study, conducted from January 17 to June 2022, encompassed 141 patients (159 procedures) who underwent modified transcanalicular diode laser dacryocystorhinostomy (MT-DCR). The procedure employed an 810-nm diode laser. Patients were monitored for at least a year after the intervention. Anatomical success was determined by ostium patency upon irrigation, while functional success referred to epiphora resolution. Parameters studied included patient demographics, procedure duration, complications, and both anatomical and functional success. Statistical analysis was performed using the Statistical Package for the Social Sciences software, with results considered significant at a 95% confidence interval (p≤0.05). Results: A total of 159 lacrimal drainage systems (141 patients: 112 women and 29 men) were included in this study. Among them, 18 underwent bilateral procedures. The average patient age was 58 years (range: 34-91 years), and the average surgical duration was 24 minutes (range: 18-35 minutes). One year after the surgery, MT-DCR exhibited anatomical and functional success rates of 84.9% (135/159) and 83% (132/159), respectively. Conclusion: MT-DCR achieved an anatomical success rate of 84.9%, reflecting an excellent outcome. However, further extensive studies with larger sample sizes and longer follow-up periods are necessary to substantiate these findings.

A new hydroxyapatite-alginate-gelatin biocomposite favor bone regeneration in a critical-sized calvarial defect model

Abstract This study aimed to evaluate the osteogenic potential of hydroxyapatite (HA), Alginate (Alg), and Gelatine (Gel) composite in a critical-size defect model in rats. Twenty-four male rats were divided into three groups: a negative control with no treatment (Control group), a positive control treated with deproteinized bovine bone mineral (DBBM group), and the experimental group treated with the new HA-Alg-Gel composite (HA-Alg-Gel group). A critical size defect (8.5mm) was made in the rat's calvaria, and the bone formation was evaluated by in vivo microcomputed tomography analysis (µCT) after 1, 15, 45, and 90 days. After 90 days, the animals were euthanized and histological and histomorphometric analyses were performed. A higher proportion of mineralized tissue/biomaterial was observed in the DBBM group when compared to the HA-Alg-Gel and Control groups in the µCT analysis during all analysis periods. However, no differences were observed in the mineralized tissue/biomaterial proportion observed on day 1 (immediate postoperative) in comparison to later periods of analysis in all groups. In the histomorphometric analysis, the HA-Alg-Gel and Control groups showed higher bone formation than the DBBM group. Moreover, in histological analysis, five samples of the HA-Alg-Gal group exhibited formed bone spicules adjacent to the graft granules against only two of eight samples in the DBBM group. Both graft materials ensured the maintenance of defect bone thickness, while a tissue thickness reduction was observed in the control group. In conclusion, this study demonstrated the osteoconductive potential of HA-Alg-Gel bone graft by supporting new bone formation around its particles.

Resumo Este estudo teve como objetivo avaliar o potencial osteogênico de um compósito de hidroxiapatita (HA), alginato (Alg) e gelatina (Gel) em um modelo de defeito de tamanho crítico em ratos. Vinte e quatro ratos machos foram divididos em três grupos: um controle negativo sem tratamento (grupo controle), um controle positivo tratado com osso bovino desproteinizado (grupo DBBM) e o grupo experimental tratado com o novo compósito HA-Alg-Gel (grupo HA-Alg-Gel). Um defeito de tamanho crítico (8,5mm) foi feito na calvária dos ratos, e a formação óssea foi avaliada por análise de microtomografia computadorizada in vivo (µCT) após 1, 15, 45 e 90 dias. Após 90 dias, os animais foram eutanasiados e análises histológicas e histomorfométricas foram realizadas. Uma maior proporção de tecido mineralizado/biomaterial foi observada no grupo DBBM quando comparado aos grupos HA-Alg-Gel e controle na análise de µCT durante todos os períodos de análise. Entretanto, não foram observadas diferenças na proporção tecido mineralizado/biomaterial no dia 1 (pós-operatório imediato) em relação aos períodos posteriores de análise em todos os grupos. Na análise histomorfométrica, os grupos HA-Alg-Gel e controle apresentaram maior formação óssea do que o grupo DBBM. Além disso, na análise histológica, cinco amostras do grupo HA-Alg-Gal exibiram espículas ósseas formadas adjacentes aos grânulos do enxerto contra apenas duas das oito amostras do grupo DBBM. Ambos os materiais de enxerto garantiram a manutenção da espessura óssea do defeito, enquanto uma redução da espessura do tecido foi observada no grupo controle. Em conclusão, este estudo demonstrou o potencial osteocondutor do enxerto ósseo de HA-Alg-Gel, promovendo a formação de osso novo ao redor das suas partículas.