Estudo histológico e imunohistoquímico da degeneração da região central da cartilagem de Meckel na mandíbula em desenvolvimento de ratos / Histological and immunohistochemical study of the degeneration of the central region of Meckel's cartilage in the developing mandible of rats

A cartilagem de Meckel é uma estrutura transitória embrionária presente durante os estágios iniciais da formação da mandíbula, localizada em toda sua extensão e dividida em três porções, anterior, intermediária e posterior. O enfoque deste trabalho foi direcionado à elucidação do destino final da porção intermediária por meio de um estudo temporal sequenciado. Por isso, foi investigado a presença de células de reabsorção e a presença de fibras colágenas, bem como da proteína óssea osteopontina (OPN) na cartilagem de Meckel na região do germe do 1º molar inferior e no seu entorno. Foram utilizados fetos de ratos Wistar em períodos gestacionais pré-estabelecidos, G18 a G21 (grupos de dias intrauterinos), bem como P0 e P1 (recém-nascidos) para remoção das cabeças. Em sequência, os espécimes foram fixados em solução de formaldeído 4% + glutaraldeído 0,1% com tampão fosfato 0,1M, descalcificados em EDTA 4,13%, desidratados em concentrações crescentes de etanol e incluídos em parafina. As amostras foram coradas em hematoxilina e eosina (HE) e tricrômico de Mallory para análise histológica. Adicionalmente, os grupos G19 a P0 foram submetidos à reação histoquímica de TRAP para determinação da presença de células clásticas. Além disso, os grupos G21 e P0 (dia do nascimento) passaram por reações de imunomarcação para análise da expressão de OPN. Foi observado a degeneração gradual da cartilagem com a observação de mudanças estruturais, a justaposição de células clásticas na superfície da cartilagem por reação histoquímica TRAP a partir do G21, o aparecimento de colágeno tipo I nas fases terminais da degeneração, assim como a marcação positiva para a osteopontina na superfície de G21 e em todo o remanescente da cartilagem de Meckel no grupo P0. O estudo apontou um processo de degeneração da cartilagem com evidências de formação de matriz mineralizada de natureza óssea, a qual foi reabsorvida por células clásticas, sugerindo a ossificação da porção intermediária da cartilagem de Meckel.

Manga traqueal cartilaginosa. Reporte de dos casos / Tracheal cartilaginous sleeve. Report of two cases

La manga traqueal cartilaginosa es una malformación de la vía aérea donde no se distinguen anillos traqueales. Un segmento continuo de cartílago se extiende desde el cricoides, pudiendo llegar hasta los bronquios principales. Está asociada a síndromes de craneosinostosis con la mutación FGFR2, además de muertes prematuras por oclusión de la tráquea con tapones mucosos. Se presenta el curso clínico de pacientes portadores de manga traqueal cartilaginosa en el contexto de una malformación craneofacial. Caso 1. Masculino, al nacer hipoplasia del tercio medio facial. Polisomnografía: índice de apnea/hipopnea de 37,7/hr. Laringotraqueobroncoscopía (LTBC): tráquea sin anillos cartilaginosos desde cricoides hasta bronquios fuentes. Se indica traqueostomía. Caso 2. Masculino, al nacer cráneo en trébol. Poligrafía: Síndrome de apnea/hipopnea obstructiva del sueño (SAHOS) leve. Revisión vía aérea: desde subglotis hasta bronquios principales se extiende tráquea en manga. Se indica traqueostomía. En el contexto de una craneosinostosis en niños, especialmente con mutación FGFR2, creemos necesario realizar una LTBC en búsqueda de manga traqueal, ya que si es diagnosticada se debe recomendar traqueostomía, mejorando su expectativa de vida. Si la indicación de traqueostomía fuese por SAHOS, es obligatoria una LTBC preoperatoria, para evitar el no tener referencias anatómicas en el proceso.

A tracheal cartilaginous sleeve is a malformation of the airway in which the tracheal rings are indistinguishable. A continuous segment of cartilage extends from the cricoid, and it may reach all the way to the main bronchi. It is associated with various craniosynostosis syndromes with the FGFR2 mutation, in addition to premature deaths due to occlusions caused by mucus plugs in the trachea. Here we present the clinical course of patients who suffer from Tracheal Cartilaginous Sleeve in the context of a craniofacial malformation. First case. Male, presenting at birth a midfacial hypoplasia. Polysomnography: presents a 37,7/h index of apnea/hypopnea. Laryngotracheobronchoscopy (LTB): trachea is without cartilaginous rings from the cricoid to the main bronchi. A tracheostomy is indicated. Second case. Male, cloverleaf skull at birth. Polysomnography: Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS) non-severe degree. Revision of the airway: the trachea in sleeve extends from the subglottis to the main bronchi. A tracheostomy is indicated. In the context of craniosynostosis in children, especially with FGFR2 mutation, we believe it is necessary to do an LTB in the search of a tracheal sleeve, since if it is diagnosed a tracheostomy must be indicated, to better the life expectancy of the patient. If the tracheostomy indication comes from an OSAHS, a preoperatory LTB is obligatory to avoid not having anatomical references during the procedure.

Systematic evaluation of the incidence of the knee donor area after autobone cartilage mosaic xentoplasty / 中国骨伤

OBJECTIVE@#To provide an overview of the incidence of knee donor -site morbidity after autologous osteochondral mosaicplasty.@*METHODS@#A comprehensive search was conducted in PubMed, EMbase, Wanfang Medical Network, and CNKI databases from January 2010 to April 20, 2021. Relevant literature was selected based on predefined inclusion and exclusion criteria, and data were evaluated and extracted. The correlation between the number and size of transplanted osteochondral columns and donor-site morbidity was analyzed.@*RESULTS@#A total of 13 literatures were included, comprising a total of 661 patients. Statistical analysis revealed an incidence of knee donor-site morbidity at 8.6% (57/661), with knee pain being the most common complaint, accounting for 4.2%(28/661). There was no significant correlation between the number of osteochondral columns and postoperative donor-site incidence (P=0.424, N=10), nor between the diameter size of osteochondral columns and postoperative donor-site incidence(P=0.699, N=7).@*CONCLUSION@#Autologous osteochondral mosaicplasty is associated with a considerable incidence of knee donor-site morbidity, with knee pain being the most frequent complaint. There is no apparent correlation between donor-site incidence and the number and size of transplanted osteochondral columns. Donors should be informed about the potential risks.

Effectiveness of anterior cruciate ligament reconstruction with personalized femoral locator based on apex of deep cartilage / 中国修复重建外科杂志

OBJECTIVE@#To investigate the effectiveness of anterior cruciate ligament (ACL) reconstruction assisted by personalized femoral locator based on the apex of deep cartilage (ADC) combined with patient imaging data.@*METHODS@#Between January 2021 and January 2022, a total of 40 patients with primary ACL rupture were selected and randomly divided into study group (ACL reconstruction assisted by personalized femoral locator based on ADC) and control group (ACL reconstruction assisted by intraoperative fluoroscopy and traditional femoral locator), with 20 cases in each group. There was no significant difference in gender, age, body mass index, affected side, cause of injury, and preoperative International Knee Documentation Committee (IKDC) score, Lyshlom score, and Tegner score between the two groups ( P>0.05). IKDC score, Lyshlom score, and Tegner score were used to evaluate the functional recovery of the affected knee before operation and at 3, 6, and 12 months after operation. CT scan and three-dimensional reconstruction were performed before and after operation to measure the horizontal distance from ADC to the anterior cartilage margin (L) and the horizontal distance from ADC to the center of the femoral canal (I), and the anteroposterior position of the bone canal (R) was calculated by I/L; the distance from the center to the distal cartilage margin (D) was measured on the two-dimensional cross section; the R value and D value were compared between the two groups.@*RESULTS@#The operation time of the study group was significantly less than that of the control group [ MD=-6.90 (-8.78, -5.03), P<0.001]. The incisions of the two groups healed by first intention, and no complication such as intra-articular infection, nerve injury, and deep vein thrombosis of lower limbs occurred. There was no significant difference in the R value and D value between the preoperative simulated positioning and the actual intraoperative positioning in the study group [ MD=0.52 (-2.85, 3.88), P=0.758; MD=0.36 (-0.39, 1.11), P=0.351]. There was no significant difference in the actual intraoperative positioning R value and D value between the study group and the control group [ MD=1.01 (-2.57, 4.58), P=0.573; MD=0.24 (-0.34, 0.82), P=0.411]. The patients in both groups were followed up 12-13 months (mean, 12.4 months). The IKDC score, Lysholm score, and Tegner score of the two groups increased gradually with time, and there were significant differences between pre- and post-operation ( P<0.05). There was no significant difference in the scores between the two groups at each time point after operation ( P>0.05).@*CONCLUSION@#The personalized femoral locator based on ADC can accurately assist the femoral tunnel positioning in ACL reconstruction, which can shorten the operation time when compared with traditional surgical methods, and achieve satisfactory early effectiveness.

Three-dimensional kinematic analysis of knee joint after anterior cruciate ligament reconstruction with personalized femoral positioner based on apex of deep cartilage / 中国修复重建外科杂志

OBJECTIVE@#To investigate the changes of knee joint kinematics after anterior cruciate ligament (ACL) reconstruction assisted by personalized femoral positioner based on the apex of deep cartilage (ADC).@*METHODS@#Between January 2021 and January 2022, a total of 40 patients with initial ACL rupture who met the selection criteria were randomly divided into the study group (using the personalized femoral positioner based on ADC design to assist ACL reconstruction) and the control group (not using the personalized femoral positioner to assist ACL reconstruction), with 20 patients in each group. Another 20 volunteers with normal knee were collected as a healthy group. There was no significant difference in gender, age, body mass index, and affected side between groups ( P>0.05). Gait analysis was performed at 3, 6, and 12 months after operation using Opti _ Knee three-dimensional knee joint motion measurement and analysis system, and the 6 degrees of freedom (flexion and extension angle, varus and valgus angle, internal and external rotation angle, anteroposterior displacement, superior and inferior displacement, internal and external displacement) and motion cycle (maximum step length, minimum step length, and step frequency) of the knee joint were recorded. The patients' data was compared to the data of healthy group.@*RESULTS@#In the healthy group, the flexion and extension angle was (57.80±3.45)°, the varus and valgus angle was (10.54±1.05)°, the internal and external rotation angle was (13.02±1.66)°, and the anteroposterior displacement was (1.44±0.39) cm, the superior and inferior displacement was (0.86±0.20) cm, and the internal and external displacement was (1.38±0.39) cm. The maximum step length was (51.24±1.29) cm, the minimum step length was (45.69±2.28) cm, and the step frequency was (12.45±0.47) step/minute. Compared with the healthy group, the flexion and extension angles and internal and external rotation angles of the patients in the study group and the control group decreased at 3 months after operation, and the flexion and extension angles of the patients in the control group decreased at 6 months after operation, and the differences were significant ( P<0.05); there was no significant difference in the other time points and other indicators when compared with healthy group ( P>0.05). In the study group, the flexion and extension angles and internal and external rotation angles at 6 and 12 months after operation were significantly greater than those at 3 months after operation ( P<0.05), while there was no significant difference in the other indicators at other time points ( P>0.05). There was a significant difference in flexion and extension angle between the study group and the control group at 6 months after operation ( P<0.05), but there was no significant difference of the indicators between the two groups at other time points ( P>0.05).@*CONCLUSION@#Compared with conventional surgery, ACL reconstruction assisted by personalized femoral positioner based on ADC design can help patients achieve more satisfactory early postoperative kinematic results, and three-dimensional kinematic analysis can more objectively and dynamically evaluate the postoperative recovery of knee joint.

Applicatoin of chitosan-based hydrogel in oral tissue engineering / 中南大学学报(医学版)

Pulpitis, periodontitis, jaw bone defect, and temporomandibular joint damage are common oral and maxillofacial diseases in clinic, but traditional treatments are unable to restore the structure and function of the injured tissues. Due to their good biocompatibility, biodegradability, antioxidant effect, anti-inflammatory activity, and broad-spectrum antimicrobial property, chitosan-based hydrogels have shown broad applicable prospects in the field of oral tissue engineering. Quaternization, carboxymethylation, and sulfonation are common chemical modification strategies to improve the physicochemical properties and biological functions of chitosan-based hydrogels, while the construction of hydrogel composite systems via carrying porous microspheres or nanoparticles can achieve local sequential delivery of diverse drugs or bioactive factors, laying a solid foundation for the well-organized regeneration of defective tissues. Chemical cross-linking is commonly employed to fabricate irreversible permanent chitosan gels, and physical cross-linking enables the formation of reversible gel networks. Representing suitable scaffold biomaterials, several chitosan-based hydrogels transplanted with stem cells, growth factors or exosomes have been used in an attempt to regenerate oral soft and hard tissues. Currently, remarkable advances have been made in promoting the regeneration of pulp-dentin complex, cementum-periodontium-alveolar bone complex, jaw bone, and cartilage. However, the clinical translation of chitosan-based hydrogels still encounters multiple challenges. In future, more in vivo clinical exploration under the conditions of oral complex microenvironments should be performed, and the combined application of chitosan-based hydrogels and a variety of bioactive factors, biomaterials, and state-of-the-art biotechnologies can be pursued in order to realize multifaceted complete regeneration of oral tissue.

Salvianolic acid A contributes to cartilage endplate cell restoration by regulating miR-940 and miR-576-5p / 中国骨伤

OBJECTIVE@#To investigate whether Salvianolic acid A (SAA) can restore cartilage endplate cell degeneration of intervertebral discs and to identify the mechanism via regulation of micro-RNA.@*METHODS@#Cartilage endplate cells were isolated from lumbar intervertebral disc surgical samples and were treated with serum containing a series of concentrations of SAA (2, 5, and 10 ?M) for 24, 48, and 72 h to identify a proper dose and treatment time of SAA. The effect SAA on interlenkin-1β (IL-1β)-induced extracellular matrix degradation of cartilage endplate cells were analyzed by Alcian blue staining and assessment of the expression levels of ADAMTS-5, MMP3 and Col2a1. Further, the potential target miRNAs were preliminarily screened by micro-RNA sequencing combining qRT-PCR and Western blot, and then, the miRNAs mimics and inhibitors were used to verify the regulatory effect of SAA on potential target miRNAs.@*RESULTS@#The 10 μM SAA treatment for 48 h significantly enhanced the viability of cartilage endplate cells, and increased Col2a1 expression and glycosaminoglycan accumulation that were repressed by IL-1β, and reduced the effect of IL-1β on ADAMTS-5, and MMP3. Screening analysis based on micro-RNA sequencing and Venny analysis identified the downstream micro-RNAs, including miR-940 and miR-576-5p. Then, the miR-940-mimic or miR-576-5p-mimic were transfected into CEPCs. Compared with the SAA group, the expression of ADAMTS-5 and MMP3 increased significantly and the expression of COL2A1 obviously decreased after overexpression of miR-940 or miR-576-5p in CEPCs.@*CONCLUSION@#Salvianolic acid A attenuated the IL-1β-induced extracellular matrix degradation of cartilage endplate cells by targeting regulate the miR-940 and the miR-576-5p.

Bone/cartilage immunomodulating hydrogels: construction strategies and applications / 中国修复重建外科杂志

OBJECTIVE@#To review the research progress in the construction strategy and application of bone/cartilage immunomodulating hydrogels.@*METHODS@#The literature related to bone/cartilage immunomodulating hydrogels at home and abroad in recent years was reviewed and summarized from the immune response mechanism of different immune cells, the construction strategy of immunomodulating hydrogels, and their practical applications.@*RESULTS@#According to the immune response mechanism of different immune cells, the biological materials with immunoregulatory effect is designed, which can regulate the immune response of the body and thus promote the regeneration of bone/cartilage tissue. Immunomodulating hydrogels have good biocompatibility, adjustability, and multifunctionality. By regulating the physical and chemical properties of hydrogel and loading factors or cells, the immune system of the body can be purposively regulated, thus forming an immune microenvironment conducive to osteochondral regeneration.@*CONCLUSION@#Immunomodulating hydrogels can promote osteochondral repair by affecting the immunomodulation process of host organs or cells. It has shown a wide application prospect in the repair of osteochondral defects. However, more data support from basic and clinical experiments is needed for this material to further advance its clinical translation process.

Primary cilia support cartilage regeneration after injury / 国际口腔科学杂志·英文版

In growing children, growth plate cartilage has limited self-repair ability upon fracture injury always leading to limb growth arrest. Interestingly, one type of fracture injuries within the growth plate achieve amazing self-healing, however, the mechanism is unclear. Using this type of fracture mouse model, we discovered the activation of Hedgehog (Hh) signaling in the injured growth plate, which could activate chondrocytes in growth plate and promote cartilage repair. Primary cilia are the central transduction mediator of Hh signaling. Notably, ciliary Hh-Smo-Gli signaling pathways were enriched in the growth plate during development. Moreover, chondrocytes in resting and proliferating zone were dynamically ciliated during growth plate repair. Furthermore, conditional deletion of the ciliary core gene Ift140 in cartilage disrupted cilia-mediated Hh signaling in growth plate. More importantly, activating ciliary Hh signaling by Smoothened agonist (SAG) significantly accelerated growth plate repair after injury. In sum, primary cilia mediate Hh signaling induced the activation of stem/progenitor chondrocytes and growth plate repair after fracture injury.

Fibrocartilaginous mesenchymoma: a clinicopathological analysis of four cases / 中华病理学杂志

Objective: To investigate the clinical, radiological, histological and molecular features and the differential diagnosis of fibrocartilaginous mesenchymoma (FM). Methods: Four cases of FM diagnosed in the Department of Pathology, the Sixth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine from 2020 to 2022 were analyzed. Related literature was also reviewed. Results: Case 1 was a 10-year-old girl with bone destruction in the sacrum and L5 articular processes revealed by CT scan. Case 2 was a 7-year-old girl with an aggressive lesion in her right distal ulna. Case 3 was an 11-year-old boy with a lesion in the metaphysis of his left proximal tibia. Case 4 was an 11-year-old boy with bone destruction in the distal portion of a radius. Microscopically, the four tumors all consisted of numerous spindle cells, hyaline cartilage nodules, and bone trabeculae. The hypocellular to moderately cellular spindle cell component contained elongated cells with slightly hyperchromatic, mildly atypical nuclei arranged in bundles or intersecting fascicles. Benign-appearing cartilaginous nodules of various sizes and shapes were scattered throughout the tumors. There were areas mimicking epiphyseal growth-plate characterized by chondrocytes arranged in parallel columns and areas of enchondral ossification. The stroma was rich in mucus in case 1. Mutation of GNAS and IDH1/IDH2 and amplification of MDM2 gene were not found in any of the three tested cases. Conclusions: FM is very rare and tends to affect young patients. It most frequently occurs in the metaphysis of long tubular bones, followed by the iliac-pubic bones and vertebrae. FM is characterized by a mixed population of spindle cells, hyaline cartilage nodules and trabeculae of bone, without specific immunophenotypes and molecular alternations. As a borderline, locally aggressive neoplasm, surgical removal with a wide margin is generally the treatment of choice for FM.

Effect of glycosaminoglycans with different degrees of sulfation on chondrogenesis / 华西口腔医学杂志

OBJECTIVES@#This study aims to investigate the effects and mechanisms of chondroitin sulfate (CS), dermatan sulfate (DS), and heparin (HEP) on chondrogenesis of murine chondrogenic cell line (ATDC5) cells and the maintenance of murine articular cartilage in vitro.@*METHODS@#ATDC5 and articular cartilage tissue explant were cultured in the medium containing different sulfated glycosaminoglycans. Cell proliferation, differentiation, cartilage formation, and mechanism were observed using cell proliferation assay, Alcian blue staining, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blot, respectively.@*RESULTS@#Results showed that HEP and DS primarily activated the bone morphogenetic protein (BMP) signal pathway, while CS primarily activated the protein kinase B (AKT) signal pathway, further promoted ATDC5 cell proliferation and matrix production, and increased Sox9, Col2a1, and Aggrecan expression.@*CONCLUSIONS@#This study investigated the differences and mechanisms of different sulfated glycosaminoglycans in chondrogenesis and cartilage homeostasis maintenance. HEP promotes cartilage formation and maintains the normal state of cartilage tissue in vitro, while CS plays a more effective role in the regeneration of damaged cartilage tissue.

Exposure to endocrine disruptors and alterations in mineralized tissues: a narrative review / Exposición a disruptores endocrinos y alteraciones en tejidos mineralizados: revisión narrativa

Background: Endocrine Disrupting Chemicals (EDCs) would cause alterations in organs/systems of exposed individuals or their progeny. Objetive: To identify and analyze the main published findings on the effects of exposure to EDCs on teeth, cartilage, and bone. Material and Methods: Two databases were analyzed: Medline and Web of Science. Only observational studies analyzing the effect of EDCs on mineralized tissues published since 2006 were included in the study. Results: 25 articles were selected, most of them involving EDCs pesticides, plasticizers, or personal care products, highlighting organochlorine compounds, bisphenols, phthalates, dioxins, parabens, and perfluoroalkyls. Thirty-six per cent of the studies reported an accumulation of EDCs in teeth or bones, while 64% reported alterations in their development or morphology, mainly at the bone level, primarily affecting their mineral density and size, as well as that of the bones of exposed individuals or their progeny. The type of effect observed was related to the EDCs analyzed, and it seemed to depend on variables such as age, sex, ethnicity/race, and even the metabolic status of the individuals in the different species analyzed. No evidence associated with effects on cartilage was found. Conclusion: EDCs in the environment, at work, or at home, under different exposure routes, are capable of accumulating in teeth and bone, particularly affecting the latter. It is necessary to study the effect of EDCs on mineralized tissues in agro-industrial areas, especially on teeth.

Antecedentes: Los Químicos Disruptores Endocrinos (EDCs) causarían alteraciones en órganos/sistemas de individuos expuestos, o su progenie. Objetivo: Identificar y analizar los principales hallazgos publicados sobre el efecto de la exposición a EDCs en dientes, cartílago y hueso. Material y Métodos: Se analizaron dos bases de datos: Medline y Web of Science, incluyendo solo estudios observacionales publicados desde el 2006, analizando el efecto de los EDCs sobre tejidos mineralizados. Resultados:25 artículos fueron seleccionados, siendo la mayoría de los EDCs pesticidas, plastificantes o productos de cuidado personal, destacando los compuestos Organo-clorados, Bisfenoles, Ftalatos, Dioxinas, Parabenos y los Perfluoroalquilos. Un 36% de los estudios reportaron un acúmulo de EDCs en dientes o huesos, mientras que un 64% informaron de alteraciones en su desarrollo o morfología, particularmente a nivel de huesos, afectando principalmente su densidad mineral y su tamaño, así como el de los individuos expuestos o su progenie. El tipo de efecto observado tuvo relación con el EDCs analizado, pareciendo depender de variables tales como edad, sexo, etnia/raza e incluso el estado metabólico de los individuos, en las diferentes especies analizadas. No se encontraron evidencias asociadas a efectos en el cartílago. Conclusión: Los EDCs en el medio ambiente, ámbito laboral o doméstico, bajo distintas rutas de exposición, son capaces de acumularse en diente y hueso, afectando particularmente a este último. Es necesario estudiar el efecto de los EDCs en los tejidos mineralizados en zonas agroindustriales, particularmente a nivel de dientes.

Progress on knee cartilage repair by knee joint distraction / 中国骨伤

Knee joint distraction is a new technology for the treatment of knee osteoarthritis in recent years. It could reduce knee pain and improve knee function, which is inseparable from the role of cartilage repair. The mechanism and influencing factors of knee joint distraction in repairing cartilage are the focus of current research. In this paper, the author reviewed literature and found that knee joint distraction could reduce knee joint load and provide a appropriate mechanical environment for cartilage repair, and it is resulting hydrostatic pressure fluctuation in the knee joint not only helps cartilage to absorb nutrients, but also promotes cartilage formation genes and inhibits cartilage matrix degrading enzyme gene expression. In addition, knee joint distraction creates conditions for synovial mesenchymal stem cells to be collected to cartilage injury, and improves ability of synovial mesenchymal stem cells to proliferate and differentiate into a chondrogenic lineage. Knee joint distraction could reduce inflammatory reaction and cartilage injury of knee joint by reducing content of inflammatory factors and inhibiting expression of inflammatory genes. At present, it is known that the factors affect repair of cartilage by knee joint distraction include, increasing weight-bearing activity and height and time of distraction is helpful for cartilage repair, male patients and patients with higher severity of knee osteoarthritis have better cartilage repair effect after knee joint distraction.The better efficacy of cartilage repair on the first year after knee joint distraction predicts a higher long-term survival rate of knee joint distraction with knee preservation. However, the research on the above hot spots is only at the initial stage and further exploration is still needed, in order to better guide clinical application of knee joint distraction.

A 3D hydrogel loaded with exosomes derived from bone marrow stem cells promotes cartilage repair in rats by modulating immunological microenvironment / 南方医科大学学报

OBJECTIVE@#To assess the efficacy of GelMA hydrogel loaded with bone marrow stem cell-derived exosomes for repairing injured rat knee articular cartilage.@*METHODS@#The supernatant of cultured bone marrow stem cells was subjected to ultracentrifugation separate and extract the exosomes, which were characterized by transmission electron microscopy, particle size analysis and Western blotting of the surface markers. The changes in rheology and electron microscopic features of GelMA hydrogel were examined after loading the exosomes. We assessed exosome release from the hydrogel was detected by BCA protein detection method, and labeled the exosomes with PKH26 red fluorescent dye to observe their phagocytosis by RAW264.7 cells. The effects of the exosomes alone, unloaded hydrogel, and exosome-loaded hydrogel on the polarization of RAW264.7 cells were detected by q-PCR and immunofluorescence assay. We further tested the effect of the exosome-loaded hydrogel on cartilage repair in a Transwell co-culture cell model of RAW264.7 cells and chondrocytes in a rat model of knee cartilage injury using q-PCR and immunofluorescence assay and HE and Masson staining.@*RESULTS@#GelMA hydrogel loaded with exosomes significantly promoted M2-type polarization of RAW264.7 cells (P < 0.05). In the Transwell co-culture model, the exosome-loaded GelMA hydrogel significantly promoted the repair of injured chondrocytes by regulating RAW264.7 cell transformation from M1 to M2 (P < 0.05). HE and Masson staining showed that the exosome-loaded hydrogel obviously promoted cartilage repair in the rat models damage.@*CONCLUSION@#GelMA hydrogel loaded with bone marrow stem cell-derived exosomes can significantly promote the repair of cartilage damage in rats by improving the immune microenvironment.

Application of microcarrier technology in cartilage repairing: a review / 生物工程学报

Cartilage has poor self-recovery because of its characteristics of no blood vessels and high extracellular matrix. In clinical treatment, physical therapy or drug therapy is usually used for mild cartilage defects, and surgical treatment is needed for severe ones. In recent years, cartilage tissue engineering technology provides a new way for the treatment of cartilage defects. Compared with the traditional surgical treatment, cartilage tissue engineering technology has the advantages of small wound and good recovery. The application of microcarrier technology in the design of tissue engineering scaffolds further expands the function of scaffolds and promotes cartilage regeneration. This review summarized the main preparation methods and development of microcarrier technology in recent years. Subsequently, the properties and specific application scenarios of microcarriers with different materials and functions were introduced according to the materials and functions of microcarriers used in cartilage repair. Based on our research on osteochondral integrated layered scaffolds, we proposed an idea of optimizing the performance of layered scaffolds through microcarriers, which is expected to prepare bionic scaffolds that are more suitable for the structural characteristics of natural cartilage.

Ankle Osteoarthritis / Osteoartrite do tornozelo

Abstract Osteoarthritis (OA) is characterized by a chronic, progressive and irreversible degradation of the joint surface associated with joint inflammation. The main etiology of ankle OA is post-traumatic and its prevalence is higher among young and obese people. Despite advances in the treatment of fractures around the ankle, the overall risk of developing posttraumatic ankle OA after 20 years is almost 40%, especially in Weber type B and C bimalleolar fractures and in fractures involving the posterior tibial border. In talus fractures, this prevalence approaches 100%, depending on the severity of the lesion and the time of follow-up. In this context, the current understanding of the molecular signaling pathways involved in senescence and chondrocyte apoptosis is fundamental. The treatment of ankle OA is staged and guided by the classification systems and local and patient conditions. The main problems are the limited ability to regenerate articular cartilage, low blood supply, and a shortage of progenitor stem cells. The present update summarizes recent scientific evidence of post-traumatic ankle OA with a major focus on changes of the synovia, cartilage and synovial fluid; as well as the epidemiology, pathophysiology, clinical implications, treatment options and potential targets for therapeutic agents.

Resumo A osteoartrite (OA) é caracterizada por uma degradação crônica, progressiva e irreversível da superfície articular, associada a inflamação articular. A principal etiologia da OA do tornozelo é pós-traumática e sua prevalência é maior entre os jovens e obesos. Apesar dos avanços no tratamento das fraturas ao redor do tornozelo, o risco geral de desenvolver OA pós-traumática do tornozelo após 20 anos do trauma é de quase 40%; especialmente nas fraturas bimaleolares de Weber tipo B e C e fraturas envolvendo a borda tibial posterior. Nas fraturas do tálus, essa prevalência se aproxima de 100%, dependendo da gravidade da lesão e do tempo de seguimento. Nesse cenário, é fundamental a compreensão atual das vias de sinalização moleculares envolvidas na senescência e apoptose dos condrócitos. O tratamento da OA do tornozelo é estagiado e guiado pelos sistemas de classificação, condições locais e do paciente. Os principais problemas são a limitada capacidade de regeneração da cartilagem articular, o baixo suprimento de sangue e a escassez de células-tronco progenitoras. A presente atualização resume evidências científicas básicas recentes da OA póstraumática do tornozelo, com foco principal nas alterações metabólicas da sinóvia, da cartilagem e do líquido sinovial. Epidemiologia, fisiopatologia, implicações clínicas, e opções de tratamento são também discutidas.

Treatment of Chondral Knee Lesions with Autologous Chondrocytes Embedded in a Fibrin Scaffold. Clinical and Functional Assessment / Tratamento de lesões condrais no joelho com condrócitos autólogos embebidos em arcabouço de fibrina. Avaliação clínica e funcional

Abstract Objective The aim of our study is to analyze the clinical and functional results obtained using autologous chondrocytes embedded in a fibrin scaffold in knee joint injuries. Methods We included 56 patients, 36 men and 20 women, with a mean age 36 years. Six of the patients were professional athletes, with single knee injuries that were either chondral or osteochondral (43 chondral, 9 osteochondral, 2 cases of osteochondritis dissecans and 2 osteochondral fractures), 2 to 10 cm2 in size and ≤ 10 mm deep, with no signs of osteoarthritis. The location of the injury was in the patella (8), the medial femoral condyle (40) and lateral femoral condyle (7) and one in the trochlea. The mean follow-up was 3 (range: 1-6) years. The clinical course was assessed using the Cincinnati and Knee Injury and Osteoarthritis Outcome (KOOS) scores, 6 and 12 months after surgery. The paired Student t-test was used to compare pre-and postoperative results. Results Six months after the implant, patients resumed their everyday activities. On the assessment scores, their condition was improving in comparison with their presurgical state (p < 0.05). They were also able to carry out their sporting activities more easily than prior to surgery (p < 0.05). Conclusion The seeding of chondrocytes in fibrin may provide a favorable microenvironment for the synthesis of extracellular matrix and improved the clinical condition and activity of the patients 1 year after surgery.

Resumo Objetivo O objetivo do nosso estudo é analisar os resultados clínicos e funcionais do tratamento de lesões nas articulações do joelho com condrócitos autólogos embebidos em arcabouço de fibrina. Métodos O estudo foi realizado com 56 pacientes (36 homens e 20 mulheres) com idade média de 36 anos; 6 indivíduos eram atletas profissionais. Os pacientes apresentavam lesões únicas, condrais ou osteocondrais (43 condrais, nove osteocondrais, 2 casos de osteocondrite dissecante e duas fraturas osteocondrais) no joelho, com 2 a 10 cm2 de tamanho e ≤ 10 mm de profundidade, sem sinais de osteoartrite. As lesões estavam localizadas na patela (8), no côndilo femoral medial (40), no côndilo femoral lateral (7) e na tróclea (1). O período médio de acompanhamento foi de 3 anos (faixa de 1-6 anos). A evolução clínica foi avaliada pelos escores de Cincinnati e Knee Injury and Osteoarthritis Outcome (KOOS), 6 e 12 meses após a cirurgia. O teste t de Student pareado foi utilizado para comparação dos achados pré e pós-operatórios. Resultados Os pacientes retomaram suas atividades diárias 6 meses após o implante. Os escores avaliados demonstraram a melhora em comparação ao estado pré-cirúrgico (p < 0,05). Além disso, os pacientes conseguiram realizar suas atividades esportivas com mais facilidade do que antes da cirurgia (p < 0,05). Conclusão A cultura de condrócitos em fibrina pode proporcionar um microambiente favorável para a síntese de matriz extracelular e melhorar a condição clínica e a atividade dos pacientes 1 ano após a cirurgia

Endoscopic tympanoplasty with inlay cartilage graft in an university hospital / Timpanoplastia endoscópica com enxerto de cartilagem inlay em hospital universitário

Abstract Introduction Tympanoplasty is the surgical procedure aimed at the reconstruction of the tympanic membrane and restoration of the sound conducting mechanism. It can be performed with several types of access and grafts and is considered successful when it achieves complete closure of the tympanic perforation and sound conduction improvement. Objective To describe the prevalence of successful closure of tympanic perforations and auditory results of endoscopic tympanoplasty with an inlay tragus cartilage graft. Methods Retrospective study developed at a tertiary referral hospital. Patients with central tympanic perforations and intact ossicular chains operated with endoscopic tympanoplasty with inlay tragus cartilage graft were included. The neo-tympanum integrity index was evaluated, and the preoperative and postoperative auditory parameters were compared using the paired Student's t-test. Results We identified 83 endoscopic tympanoplasties with inlay cartilage, of which 63 (76 %) had an intact neo-tympanum and 20 (24 %) had residual perforations. The preoperative air-bone gap was, on average, 18 ± 8.9 dBHL, and the postoperative 11 ± 10 dBHL (p = 0.0005), showing reduction in 71 % and complete recovery in 27 %. The mean preoperative speech recognition threshold was 35 ± 13.5 and the postoperative SRT was 27 ± 14.4 (p = 0.0002). The preoperative tritonal mean was 34 ± 14.3 and the postoperative was 24 ± 15 (p = 0.0002). Conclusion In this series, endoscopic tympanoplasties with inlay tragus cartilage graft showed a 76 % prevalence of complete closure of the tympanic perforation, with significant improvement in the auditory parameters.

Resumo Introdução Timpanoplastia é o procedimento cirúrgico voltado para a reconstrução da membrana timpânica e restauração do mecanismo condutor do som. Pode ser executada através de diversos tipos de acesso e de enxertos e é considerada bem-sucedida quando obtém fechamento completo da perfuração timpânica e melhoria na condução sonora. Objetivo Descrever a prevalência de sucesso no fechamento completo das perfurações timpânicas e os resultados auditivos das timpanoplastias endoscópicas com enxerto de cartilagem de tragus inlay. Metodologia Estudo retrospectivo desenvolvido em hospital terciário de referência. Pacientes com perfurações timpânicas centrais e com cadeias ossiculares íntegras submetidos a timpanoplastias endoscópicas com enxerto de cartilagem de tragus inlay foram incluídos. Foram avaliados o índice de integridade do neotímpano e os parâmetros auditivos pré e pós-operatórios foram comparados com o teste t de Student pareado. Resultados Foram identificadas 83 timpanoplastias endoscópicas com cartilagem inlay, 63 (76%) obtiveram neotímpano íntegro e 20 (24%), perfurações residuais. O gap aéreo-ósseo pré-operatório foi, em média, 18 ± 8,9 dBNA e o pós-operatório 11 ± 10 dBNA (p = 0,0005), sofreu redução em 71% e recuperação completa em 27%. O SRT pré-operatório médio foi 35 ± 13,5 e o pós-operatório 27 ± 14,4 (p = 0,0002). A média tritonal pré-operatória foi 34 ± 14,3 e a pós-operatória 24 ± 15 (p = 0,0002). Conclusão Nesta casuística, as timpanoplastias endoscópicas com cartilagem de tragus inlay apresentaram fechamento completo da perfuração timpânica em 76% dos casos, com melhoria significativa dos parâmetros auditivos.

Evaluation of the CTX-II Biomarker in Patients with Anterior Cruciate Ligament Tear: Pilot Study / Avaliação do biomarcador CTX-II em pacientes com ruptura do ligamento cruzado anterior: Estudo piloto

Abstract Objective The aim of the present study was to quantify the urinary concentration of the C-terminal cross-linked telopeptide of type-II collagen (CTX-II) biomarker in patients who suffered an isolated ACL injury, and to compare the concentrations found in this population with a control group of patients with no metabolic changes in the knee that could lead to cartilage degeneration. Methods A cross-sectional pilot study was performed in two groups: patients with ACL tears and a control group (each group with 10 male subjects, with an age range between 18 and 35 years, and body mass index below 30 kg/m2). In both groups, urine concentrations of a biomarker related to the degradation of type-II collagen (CTX-II) was measured. For the group with ACL tears, a temporal relationship between the time after the injury and the amount of the biomarker was also examined. Results There were significant differences in the concentrations of urinary CTX-II between the ACL group and the control group (p = 0.009). No significant relationship was observed between the time after the injury and the quantity of the biomarker. Conclusions Patients with ACL injury had higher concentrations of urinary CTX-II biomarker than those with no ACL injury (p = 0.009). However, there was no correlation between the concentration of this biomarker and the elapsed time after the injury (p≥ 0.05).

Resumo Objetivo Quantificar a concentração urinária do biomarcador telopeptídeo C de ligação cruzada de colágeno de tipo II (C-terminal cross-linked telopeptide of type-II collagen, CTX-II) em casos de lesão isolada do ligamento cruzado anterior (LCA), e comparar as concentrações observadas nessa população com um grupo controle composto por pacientes sem alterações metabólicas no joelho que possam levar à degeneração da cartilagem. Métodos Este é um estudo piloto transversal com dois grupos: pacientes com ruptura do LCA e grupo controle (cada grupo era composto por 10 indivíduos do sexo masculino, com 18 a 35 anos de idade, e índice de massa corporal inferior a 30 kg/m2). Nos dois grupos, as concentrações urinárias de um biomarcador relacionado à degradação do colágeno de tipo II (CTX-II) foram medidas. No grupo com ruptura do LCA, a relação entre o tempo pós-lesão e a quantidade do biomarcador também foi analisada. Resultados Houve diferenças significativas nas concentrações urinárias de CTX-II entre o grupo LCA e o grupo controle (p = 0,009). Não foi observada relação significativa entre o tempo de lesão e a quantidade do biomarcador. Conclusões Pacientes com lesão do LCA apresentaram maiores concentrações urinárias do biomarcador CTX-II do que aqueles sem lesão do LCA (p = 0,009). No entanto, não houve correlação entre a concentração desse biomarcador e o tempo decorrido após a lesão (p≥ 0,05).

Rates of success in hearing and grafting in the perichondrium-preserved palisade island graft technique / Taxas de sucesso na audição e em timpanoplastias com a técnica de enxerto de cartilagem em ilha e paliçada preservado em pericôndrio

Abstract Introduction Various graft materials have been used in the tympanoplasty technique. Cartilage grafts are being used increasingly in recent years. Objective The aim of this study was to present the comparative outcomes of the perichondrium-preserved palisade island graft technique previously defined by ourselves. Methods We retrospectively compared the hearing and graft success rates in 108 patients with chronic otitis media, who had undergone cartilage tympanoplasty, where both island and perichondrium-preserved palisade graft techniques were used. Results The success rates among the study and the control groups with regard to graft take were 97% and 93%, respectively. No significant difference was observed between the groups with regard to the postoperative mean pure tone values, improvement in air-bone gaps and reduction in air-bone gaps to under 20 dB. However, better results were observed in the study group. Conclusion The perichondrium-preserved palisade island graft technique is an easy method with high graft success rates and hearing outcomes.

Resumo Introdução Vários materiais de enxerto têm sido usados na realização de timpanoplastias. Nos últimos anos, os enxertos de cartilagem têm sido cada vez mais usados. Objetivo Apresentar os resultados comparativos da técnica de enxerto de cartilagem em ilha associada e paliçada preservado em pericôndrio previamente descrita pelos autores. Método Foram comparadas retrospectivamente as taxas de sucesso auditivo e na "pega" do enxerto em 108 pacientes com otite média crônica, submetidos a timpanoplastia com cartilagem, na qual foram usadas ambas as técnicas, de enxerto em ilha e paliçada preservado em pericôndrio. Resultados As taxas de sucesso entre os grupos de estudo e controle em relação à "pega" do enxerto foram de 97% e 93%, respectivamente. Não foi observada diferença significante entre os grupos em relação aos valores médios dos tons puros, melhoria do gap ou redução do aéreo-ósseo para menos de 20 dB no pós-operatório. No entanto, melhores resultados foram observados no grupo de estudo. Conclusão A técnica de enxerto em ilha associada e paliçada preservado em pericôndrio é um métodofácil, com altas taxas de sucesso tanto do enxerto quanto dos resultados auditivos.