Estudio retrospectivo de 544 timpanoplastias con cartílago y pericondrio: resultados anatómicos y funcionales / A retrospective study of 544 tympanoplasty with cartilage and perichondrium: anatomical and functional results

Introducción: el cierre de las perforaciones timpánicas se realiza con diferentes materiales, entre ellos el cartílago y el pericondrio. En este estudio se compararon los resultados anatómicos y funcionales obtenidos con ambos materiales, y se evaluaron posibles factores asociados con los buenos resultados. Material y métodos: estudio retrospectivo en pacientes intervenidos de timpanoplastia sin mastoidectomía entre el 1 de enero de 2001 y el 31 de diciembre de 2018. Resultados: se incluyeron 544 timpanoplastias. En la mayoría se utilizó cartílago (78,5 %) y en el resto pericondrio. El cartílago se utilizó con mayor frecuencia en los menores de 18 años (p=0,001), perforaciones totales y subtotales (p=0,000) y timpanoplastias secundarias y terciarias (p=0,008). No hubo diferencias en el tiempo de seguimiento (15,68 ± 22,18 meses frente al 12,86 ± 14,9 meses, p=0,169). La tasa de éxito anatómico fue mayor en el grupo de cartílago, sin diferencias en los resultados auditivos (82 % con cartílago y 78,3 % con pericondrio). El éxito anatómico se relacionó con la técnica utilizada para la reconstrucción con cartílago, mientras que los resultados auditivos se asociaron significativamente con el estado de la mucosa del oído medio y la cadena de huesecillos en el momento de la cirugía y el éxito anatómico posquirúrgico. Conclusiones: con el cartílago se consiguieron mejores resultados anatómicos que con el pericondrio, sin diferencias a nivel funcional. Sin embargo, los resultados funcionales empeoraron si había patología a nivel del oído medio y en ausencia de restauración anatómica.

Introduction: Different materials are used to close tympanic perforations. This stu-dy aimed to compare anatomical results obtained with cartilage and perichondrium and evaluate factors associated with successful results. Material and method: Re-trospective study of patients who underwent tympanoplasty without mastoidectomy between January 1, 2001, and December 31, 2018. Demographic data, ear pathology, surgical intervention, and anatomical and functional results were collected. Results:544 tympanoplasty were included. Cartilage was the most used (78.5%). Cartilage was used more frequently in children under 18 years (p = 0.001), to reconstruct total and subtotal perforations (p = 0.000) and in secondary and tertiary tympanoplasty (p = 0.008). Follow-up time did not differ between the two groups (15.68 ± 22.18 months vs. 12.86 ± 14.9 months, p = 0.169). The anatomical success rate was higher in the cartilage group, with no significant differences in hearing outcomes (82% with cartilage and 78.3% with perichondrium). Anatomical success was related to the technique used for cartilage reconstruction (monoblock or palisade). Hearing re-sults were significantly associated with the state of middle ear mucosa at the time of surgery, the state and mobility of the ossicle chain, and post-surgical anatomical suc-cess. Conclusions: Cartilage achieved better anatomical results than perichondrium. Both materials were comparable on a functional level. However, the functional re-sults worsen if there is pathology of the middle ear (mucosa or chain of ossicles) and anatomical restoration is not achieved.

Reconstrução nasal com uso de costela em paciente com síndrome de Binder: Um relato de caso e revisão de literatura / Nasal reconstruction using ribs in a patient with Binder syndrome: A case report and literature review

Introdução: A síndrome de Binder também pode ser conhecida como displasia maxilonasal e é uma malformação congênita caracterizada por hipoplasia nasomaxilar devido a um subdesenvolvimento do esqueleto facial médio. A atual incidência ou prevalência ainda é desconhecida, mas afeta aproximadamente um recém-nascido vivo em cada 10.000 nascimentos. O diagnóstico pode ser clínico ou associado a ultrassonografia pré-natal, caracterizada por nariz achatado e convexidade anormal da maxila. O tratamento é cirúrgico para correção das anormalidades estéticas e funcionais. Relato de Caso: Paciente que recebeu diagnóstico de síndrome de Binder aos 14 anos, sem outras malformações associadas, com queixa estética e funcional nasal. A correção cirúrgica foi iniciada pela extração de um bloco da sexta cartilagem costal à esquerda, com abertura nasal na margem columelar, no padrão de uma rinoplastia aberta, e dissecados os tecidos no plano subSMAS. Após preparo da área receptora nasal, foram esculpidos bloco de cartilagem para reconstrução do dorso nasal, enxertos alares e enxerto de cartilagem septal. Houve melhora de projeção da ponta nasal e alongamento nasal. Conclusão: A rinoplastia pode ser uma cirurgia desafiadora nesses pacientes, sendo a reconstrução autóloga com o uso de cartilagem costal indicada pela literatura como a melhor opção. É necessário individualizar cada caso para programação de enxertos e reestruturação nasal, sendo fundamental também a melhora funcional desses casos.

Introduction: Binder's syndrome can also be known as maxillonasal dysplasia and it is a congenital malformation characterized by nasomaxillary hypoplasia resulting from an underdevelopment of the middle facial skeleton. The current incidence or prevalence is still unknown, but it affects approximately one child in every 10,000 births. The diagnosis can be clinical or associated with prenatal ultrasonography, characterized by a flattened nose and abnormal maxillary convexity. The treatment is surgical to correct aesthetic and functional abnormalities. Case Report: Patient diagnosed with Binder's syndrome at the age of 14, without other associated malformations, with aesthetic and functional nasal complaints. Surgical correction began with the extraction of a block of the sixth costal cartilage on the left, with a nasal opening on the columellar margin, in the pattern of an open rhinoplasty, and tissue dissection in the sub-SMAS plane. After preparing the nasal receptor area, a block of cartilage was sculpted for reconstruction of the nasal dorsum, alar grafts and septal cartilage grafts. There was an improvement in the projection of the nasal tip and nasal dorsum. Conclusion: Rhinoplasty can be a challenging surgery in these patients, and the literature indicates that the best option is autologous reconstruction with costal cartilage. It is necessary to individualize each case to schedule nasal grafts and restructuring, and functional improvement in these cases is also essential

Refixation of the Excised Acetabular Labrum can Affect the Structural Changes of Cartilage Surface in the Hip Joint / La Refijación del Labrum Acetabular Extirpado Puede Afectar los Cambios Estructurales de la Superficie del Cartílago en la Articulación Coxal

SUMMARY: Refixation of the damaged acetabular labrum is a method of surgical treatment of the hip joint that can promote the repair of joint function after injury and prevent premature osteoarthritis. We sought to determine the condition of the hip joint in rabbits 4 months after excision of the acetabular labrum and the condition of the joint after labral refixation. The articular cartilage of the femoral head and acetabulum was examined by histological methods, multipoint measurement of cartilage thickness, and the ratio between cartilage matrix and chondrocytes lacunae, and the condition of cartilage according to the OARSI grading scale was carried out. On this model, a correlation analysis was performed between the results of the OARSI grading scale and the data of linear morphometry. All these parameters made it possible to better assess changes in articular cartilage. The ratio between matrix and chondrocyte lacunae turned out to be a method that allows establishing early cartilage damage when erosion, fibrosis or deformation did not occur. We found significant differences between the condition of the cartilage after exicion of acetabular labrum and after labral refixation, which give hope to confirm that this surgical technique can delay or prevent progressive changes in the cartilage of the damaged hip joint.

La refijación del labrum acetabular dañado es un método de tratamiento quirúrgico de la articulación coxal, que puede promover la reparación de la función articular después de una lesión y prevenir la osteoartritis prematura. Intentamos determinar el estado de la articulación coxal en conejos de 4 meses después de la escisión del labrum acetabular y observar el estado de la articulación después de la refijación del labrum. El cartílago articular de la cabeza femoral y el acetábulo se examinó por métodos histológicos, se midió a través de multipunto el grosor del cartílago y se realizó la relación entre la matriz del cartílago y las lagunas de condrocitos, y se llevó a cabo la condición del cartílago según la escala de clasificación OARSI. Sobre este modelo se realizó un análisis de correlación entre los resultados de la escala de calificación OARSI y los datos de la morfometría lineal. Todos estos parámetros permitieron evaluar mejor los cambios en el cartílago articular. La relación entre la matriz y las lagunas de condrocitos resultó ser un método que permite establecer temprano el daño del cartílago cuando no se presentó erosión, fibrosis o deformación. Encontramos diferencias significativas entre la condición del cartílago después de la extirpación del labrum acetabular y después de la refijación del labrum, lo que da la esperanza de confirmar que esta técnica quirúrgica puede retrasar o prevenir cambios progresivos en el cartílago de la articulación coxal dañada.

Treatment of Chondral Lesions in the Knee / Tratamento das lesões condrais no joelho

Abstract Articular cartilage injuries are common and lead to early joint deterioration and osteoarthritis. Articular cartilage repair techniques aim at forming a cartilaginous neo-tissue to support the articular load and prevent progressive degeneration. Several techniques are available for this purpose, such as microfracture and chondrocyte transplantation. However, the procedural outcome is often fibrocartilage, which does not have the same mechanical resistance as cartilaginous tissue. Procedures with autologous osteochondral graft have a morbidity risk, and tissue availability limits their use. As such, larger lesions undergo osteochondral transplantation using fresh or frozen grafts. New techniques using minced or particulate cartilage fragments or mesenchymal stem cells are promising. This paper aims to update the procedures for treating chondral lesions of the knee.

Resumo As lesões da cartilagem articular são comuns e levam à deterioração precoce da articulação e ao desenvolvimento da osteoartrite. As técnicas de reparo da cartilagem articular visam a formação de um neo-tecido cartilaginoso capaz de suportar carga articular e evitar a progressão da degeneração. Há várias técnicas disponíveis para esse fim, como a microfratura e o transplante de condrócitos. Entretanto muitas vezes o desfecho do procedimento é a formação de fibrocartilagem, que não possui a mesma resistência mecânica do tecido cartilaginoso. Em outros procedimentos, nos quais é realizado enxerto osteocondral autólogo, há risco de morbidade associada ao procedimento, além da disponibilidade limitada de tecido. Por esse motivo, o transplante osteocondral, utilizando enxertos a fresco ou congelados tem sido utilizado para lesões de maior volume. Por fim, novas técnicas utilizando fragmentos de cartilagem picada ou particulada, assim como o uso de células tronco mesenquimais se apresentam como promissores. O objetivo desse artigo é realizar uma atualização dos procedimentos para tratamento das lesões condrais do joelho.

Child Fractures: Are We Getting More Surgical? / Fraturas na criança: Estamos ficando mais cirúrgicos?

Abstract Historically, surgeries on the immature skeleton were reserved for open or articular fractures. In recent years, the improvement in the quality and safety of anesthesia, new imaging equipment, implants designed especially for pediatric fractures, associated with the possibility of shorter hospitalization time and rapid return to social life has demonstrated a new tendency to evaluate and treat fractures in children. The purpose of this update article is to answer the following questions: (1) Are we really turning more surgical in addressing fractures in children? (2) If this is true, is this surgical conduct based on scientific evidence? In fact, in recent decades, the medical literature demonstrates articles that support better evolution of fractures in children with surgical treatment. In the upper limbs, this is very evident in the systematization of the reduction and percutaneous fixation of supracondylar fractures of the humerus and fractures of the forearm bones. In the lower limbs, the same occurs with diaphyseal fractures of the femur and tibia. However, there are gaps in the literature. The available published studies show low scientific evidence. Thus, it can be inferred that, even though the surgical approach is more present, the treatment of pediatric fractures should always be individualized and conducted according to the knowledge and experience of the professional physician, taking into account the presence of technological resources available for the care of the small patient. All possibilities, non-surgical and/or surgical, should be included, always instituting actions based on science and in agreement with the family's wishes.

Resumo Historicamente, as cirurgias no esqueleto imaturo eram reservadas às fraturas expostas ou articulares. Nos últimos anos, a melhora na qualidade e segurança das anestesias, novos equipamentos de imagem, implantes desenhados especialmente para fraturas pediátricas, associados à possibilidade de menor tempo de hospitalização e rápido retorno ao convívio social vêm demonstrando uma nova tendência de avaliar e tratar fraturas na criança. O objetivo deste artigo de atualização é responder às seguintes questões: (1) estamos realmente ficando mais cirúrgicos na abordagem das fraturas em crianças? (2) Caso isto seja verdadeiro, esta conduta cirúrgica está baseada em evidências científicas? De fato, nas últimas décadas, a literatura médica demonstra artigos que suportam melhor evolução das fraturas na criança com o tratamento cirúrgico. Nos membros superiores, isto fica muito evidente na sistematização da redução e fixação percutânea das fraturas supracondilianas do úmero e das fraturas de ossos do antebraço. Nos membros inferiores, o mesmo ocorre com fraturas diafisárias do fêmur e tíbia. No entanto, há lacunas na literatura. Os estudos publicados são geralmente com baixa evidência científica. Assim, pode-se deduzir que, mesmo sendo a abordagem cirúrgica mais presente, o tratamento de fraturas pediátricas deve ser sempre individualizado e conduzido de acordo com o conhecimento e experiência do médico profissional, levando em conta a presença de recursos tecnológicos disponíveis para o atendimento do pequeno paciente. Deve-se incluir todas as possibilidades, não cirúrgicas e/ou cirúrgicas, sempre instituindo ações baseadas na ciência e em concordância com os anseios da família.

Study of developing tracheal cartilage under light microscope

Background: Airway formation is one of the earliest events in development of respiratory system. However, maturation of airway continues well in post-natal life. The trachea has framework of incomplete ring of hyaline cartilage united by fibrous tissue and smooth muscle through which air conduction takes place. The trachea-bronchial mucosa is target for host of airborne toxic agents; bacterial and viral agents, allergens, reactive gases, aerosols, and irritant particles. This fascinates many workers for detailed study of epithelium or lining air passage. Aims and Objectives: The present study was undertaken to document normal developmental microscopic structure of tracheal cartilage in fetuses of different age group (gestational ages between 12th and 40th weeks) and to compare the difference between different age groups. Materials and Methods: Tissues from trachea of various age group fetuses were collected, processed, and stained with H and E and Masson’s trichrome. Results: Development of tracheal cartilage was observed into three trimesters. The 2nd and 3rd trimesters were further divided in the early 2nd (13th–16th weeks), mid-2nd (17th–20th weeks), late 2nd (21st–24th weeks), early 3rd (25th–28th weeks), mid-3rd (29th–32nd weeks), and late 3rd (33rd–40th weeks) phases. Conclusion: Perichondrium of cartilage had shown well-marked outer fibrous layer with increased vascularity by late 2nd to early 3rd trimester. Well-marked inner cellular layer of perichondrium was noticed by 3rd trimester, while cartilage had shown active chondrocytes by late 2nd to early 3rd trimester. At the late 3rd trimester, typical hyaline cartilage had shown chondrocytes in cell nest surrounded by territorial matrix.

Evaluation of knee cartilage based on MRI artificial intelligence reconstruction model of knee joint / 中华骨科杂志

Objective:To explore the feasibility of the AI intelligent reconstruction model based on knee joint magnetic resonance data developed by Nuctech Company Limited for evaluating knee cartilage injury.Methods:Thirty-three patients (a total of forty-one knees) who were hospitalized with severe knee osteoarthritis in Beijing Tsinghua Changgung Hospital from May 2021 to April 2022 were selected. All of them were planned to be performed total knee arthroplasty (TKA) for the treatment of knee osteoarthritis. Fifteen males with an average age of 71±5 years old and twenty six females with an average age of 71±9 years old were included in this study. There were 19 cases of left knee and 22 cases of right knee. Thin layer MRI examination on the patients' knee joints was performed before the surgery, and artificial intelligence model based on the thin layer MRI data of the knee joint was reconstructed. The cartilage part of the model was selected and corrected by Principal Component Analysis (PCA) in order to realize model straightening. The tibial plateau cartilage of knee joint which intercepted during operation was classified according to the International Cartilage Repair Society (ICRS). Finally the results were compared with the ICRS classification results of knee artificial intelligence reconstruction model and artificial recognition of knee joint MRI images.Results:Compared with the grade of cartilage injury intercepted during our operation which was according to the ICRS classification, the sensitivity of artificial intelligence reconstruction model for the diagnosis of cartilage injury with ICRS classification grade four was 93.1%. The specificity of artificial intelligence reconstruction model was 91.4%. The positive predictive value (PPV) of artificial intelligence reconstruction model was 92.2%. And the negative predictive value (NPV) of artificial intelligence reconstruction model was 80.3%. The area under ROC curve (AUC) was 0.92. The ICRS classification consistency between artificial intelligence model and physical inspection results was good with kappa value 0.81 ( P<0.001) . In the aspect of artificial recognition of cartilage injury grading in MRI images, the sensitivity of artificial recognition was 92.10% compared with the manual identification of cartilage injury classification in MRI images. The specificity of artificial recognition was 91.60%. The positive predictive value (PPV) of artificial recognition was 97.20% and the negative predictive value (NPV) of artificial recognition was 78.8%. The kappa value of the cartilage injury classification in MRI images consistency between artificial recognition and manual identification was 0.79 ( P<0.001). Conclusion:Based on the evaluation of cartilage injury by AI reconstruction model of knee joint, the sensitivity and specificity of the diagnosis of ICRS grade IV cartilage injury can be acceptable, but still needs to be improved.

Recent advances of acellular cartilage matrix in cartilage regeneration / 中华骨科杂志

Osteoarthritis is a common degenerative joint disease, and cartilage damage is often considered an early factor in irreversible joint degeneration. Repairing damaged cartilage remains a medical challenge due to its limited ability to self-repair and regenerate. In recent years, the application of tissue engineering strategies to treat cartilage defects has been recognized as an emerging therapeutic avenue. Acellular cartilage matrix (ACM) is an ideal material for cartilage repair and regeneration as it retains the extracellular matrix structure and bioactive components of natural cartilage, mimicking the extracellular environment of natural cartilage to the greatest extent. Type II collagen is the main type of hyaline cartilage and plays an important role in regulating the mechanical properties of cartilage tissue. It has been shown that type II collagen, growth factors and the hypoxic microenvironment play important roles in promoting cartilage regeneration. Type II collagen induces cell aggregation and chondrogenic differentiation in a specific way; Various growth factors contained in the ACM induce Sox9 expression and promote chondrogenic differentiation of stem cells; The hypoxic microenvironment upregulates the expression of type II collagen (COL2A1), Sox9 and maintains chondrocyte phenotype. In addition, ACM has been widely used in cartilage regeneration studies, either as a decellularized scaffold, hydrogel or 3D bioprinting technique for the repair of defective cartilage. Although the ACM-derived biomaterials discussed in this paper have many advantages, there are still some difficulties in their practical applications, such as loss of ACM components and reduced scaffold performance, which are still worth exploring in depth.

Orthotopic osteochondral transplantation for the treatment of femoral head compression fracture: a case report and literature review / 中华骨科杂志

Femoral head fracture is commonly seen in high-energy injury. However, compression fracture of femoral head is more rare. In most classifications of femoral head fracture, the compression is unusually involved. A case about acute traumatic dislocation of hip joint with compression fracture of femoral head is reported, involving a patient who hurt himself by riding electric bike and hitting the flower bed. He came to our hospital complaining of pain and limited motion of his right leg. The diagnosis of right hip anterior dislocation with the compression fracture of femoral head was confirmed by medical history, physical examination and imaging. Closed reduction of hip dislocation was performed in an emergency. Then we transplanted the bone cartilage from the non-weight-bearing area under the femoral head to the collapsed weight-bearing area, fixing it with countersunk hollow screws, and then the non-weight-bearing donor area was reconstructed with autogenous iliac bone, using surgical hip dislocation. The anatomical structure of the femoral head was therefore restored successfully during the operation. Three months after surgery, the X-ray showed that the femoral head was smooth and the cartilage graft was well fixed. Eight months after surgery, the patient gradually increased the bearing weight from partial to full according to his own condition, and there was no obvious pain in hip. After 24-month follow-up, we found the X-rays showed good reduction and fixation of the femoral head fracture. The CT scan showed no necrosis or cystic degeneration. He got well-active and passive movement in hip joint, and got no pain when walking with burden. For the patient with hip dislocation and compression fracture of femoral head, early joint reduction and non-weight-bearing osteocartilage transplantation can restore the anatomical structure of the weight-bearing area of the femoral head, to avoid traumatic osteoarthritis, and to improve the long-term quality of life of patients.

Expert consensus on platelet-rich plasma treatment for osteochondral lesion of talus (version 2023) / 中华创伤杂志

Osteochondral lesion of talus (OLT) is a foot and ankle disease characterized by ankle pain, which may impact the joint function and life quality. If managed improperly, it may lead to a further ankle arthritis, severely compromising the prognosis. The therapeutic effect of conservative treatment for OLT is still uncertain. Surgery is still the main treatment modality for OLT with various techniques. However, the optimized surgical technique is still inconclusive, furthermore, regeneration and repair of cartilage after debridement is also a great challenge for the treatment of OLT. Platelet-rich plasma (PRP) with good repair effect on cartilage injury is gradually applied in the treatment of OLT. However, there still lacks the unified understanding of the technique and specification of PRP for the treatment of OLT. Therefore, National Orthopedics Center of Shanghai Sixth People′s Hospital allied Foot Ankle Basic Research & Orthopedics Group, Chinese Association of Orthopedic Surgeons; Foot and Ankle Committee of Chinese Association of Sports Medicine Physicians; and Foot and Ankle Group of Orthopedic Specialized Branch of Shanghai Medical Association to organize related experts to formulate the Expert consensus on platelet- rich plasma treatment for osteochondral lesion of talus ( version2023). Fifteen recommendations were put forward upon PRP preparation, indications, contraindications and treatment methods of PRP for OLT, so as to standardize the PRP treatment for OLT.

Clinical analysis of otoendoscopic myringoplasty with tragus perichondrium in 20 cases / 中国基层医药

Objective:To analyze the clinical application effect of otoendoscopic myringoplasty with tragus perichondrium.Methods:The clinical data of 20 patients with tympanic membrane perforation who received treatment in Suixian Traditional Chinese Medicine Hospital from March 2019 to March 2020 were retrospectively analyzed. Among the 20 patients, 6 patients had traumatic tympanic membrane perforation, and 14 patients had tympanic membrane perforation caused by chronic suppurative otitis media (stationary phase). All patients underwent otoendoscopic myringoplasty with tragus perichondrium. After surgery, the healing of tympanic membrane perforation and the improvement of hearing were evaluated.Results:After surgery, all patients were followed up for 12 months. Traumatic tympanic membrane perforation healed in six patients. The tympanic membrane grafts survived in 12 patients with tympanic membrane perforation caused by chronic suppurative otitis media (stationary phase). One patient had poor postoperative healing and the remaining small perforation healed after secondary treatment under local anesthesia. Healing from tympanic membrane perforation was not achieved in one patient because of perforation caused by otitis media. The healing rate of tympanic membrane perforation caused by chronic suppurative otitis media was 95%. Before surgery, the air conduction pure tone hearing threshold was (42 ± 11) dBHL, and it was (25 ± 10) dBHL 12 months after surgery. There was a significant difference in air conduction pure tone hearing threshold between before and after surgery ( t = 4.00, P < 0.05). No complications such as tragus cartilage infection, skin flap necrosis of external auditory meatus, peripheral facial paralysis, hearing loss, or tinnitus occurred in 20 patients with tympanic membrane perforation. Conclusion:Otoendoscopic myringoplasty with tragus perichondrium leads to a high perforation healing rate, improves healing greatly, has no serious complications, produces minimal trauma, and contributes to a rapid recovery from tympanic membrane perforation.

Roles of focal adhesion proteins in skeleton and diseases

The skeletal system, which contains bones, joints, tendons, ligaments and other elements, plays a wide variety of roles in body shaping, support and movement, protection of internal organs, production of blood cells and regulation of calcium and phosphate metabolism. The prevalence of skeletal diseases and disorders, such as osteoporosis and bone fracture, osteoarthritis, rheumatoid arthritis, and intervertebral disc degeneration, increases with age, causing pain and loss of mobility and creating a huge social and economic burden globally. Focal adhesions (FAs) are macromolecular assemblies that are composed of the extracellular matrix (ECM), integrins, intracellular cytoskeleton and other proteins, including kindlin, talin, vinculin, paxillin, pinch, Src, focal adhesion kinase (FAK) and integrin-linked protein kinase (ILK) and other proteins. FA acts as a mechanical linkage connecting the ECM and cytoskeleton and plays a key role in mediating cell-environment communications and modulates important processes, such as cell attachment, spreading, migration, differentiation and mechanotransduction, in different cells in skeletal system by impacting distinct outside-in and inside-out signaling pathways. This review aims to integrate the up-to-date knowledge of the roles of FA proteins in the health and disease of skeletal system and focuses on the specific molecular mechanisms and underlying therapeutic targets for skeletal diseases.

Reprogrammed siTNFα/neutrophil cytopharmaceuticals targeting inflamed joints for rheumatoid arthritis therapy

Rheumatoid arthritis (RA) is an autoimmune disease characterized by severe synovial inflammation and cartilage damage. Despite great progress in RA therapy, there still lacks the drugs to completely cure RA patients. Herein, we propose a reprogrammed neutrophil cytopharmaceuticals loading with TNFα-targeting-siRNA (siTNFα) as an alternative anti-inflammatory approach for RA treatment. The loaded siTNFα act as not only the gene therapeutics to inhibit TNFα production by macrophages in inflamed synovium, but also the editors to reprogram neutrophils to anti-inflammatory phenotypes. Leveraging the active tendency of neutrophils to inflammation, the reprogrammed siTNFα/neutrophil cytopharmaceuticals (siTNFα/TP/NEs) can rapidly migrate to the inflamed synovium, transfer the loaded siTNFα to macrophages followed by the significant reduction of TNFα expression, and circumvent the pro-inflammatory activity of neutrophils, thus leading to the alleviated synovial inflammation and improved cartilage protection. Our work provides a promising cytopharmaceutical for RA treatment, and puts forward a living neutrophil-based gene delivery platform.

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.

Natural reversal of mandibular condylar cartilage histological damage caused by chronic unpredictable moderate stress in rats / 口腔疾病防治

Objective @#To investigate the histological damage recovery of temporomandibular joint condylar cartilage caused by chronic unpredictable moderate stress, aiming to provide an experimental basis for the prevention and treatment of temporomandibular disorder.@*Methods @#This animal experiment was approved by the Laboratory Animal Ethical Inspection, School of Stomatology, The Fourth Military Medical University (No. 2020081). 60 male SD rats were randomly divided into control group, stress group, and 2-, 4- and 8-week post-stress recovery groups. Rats were subjected to chronic unpredictable moderate stress (CUMS) for 8 weeks including damp sawdust for 24 hours, tilted cage for 12 hours, noise for 4 hours, light/dark cycle reversal, water immersion, tail clamp, and restraint stress. The serum assessment, behavioral tests, histological and ultrastructural observation were performed 2-, 4- and 8-weeks after stress factors were removed. Serum levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were determined with ELISA. The sucrose preference test (SPT) and the forced swim test (FST) were used to assess the depressive-like behavior. The expression level of interleukin-1α (IL-1α) and matrix metalloproteinases-3 (MMP-3) were determined by Immunohistochemistry and Western blot.@*Results @#At the end of 8 weeks of CUMS, the serum levels of CORT and ACTH were significantly higher in stress group compared with control group (P<0.01). The sucrose preference decreased significantly and the immobility time increased significantly in the stressed rats compared with those in the control group, indicating a successful establishment of CUMS. The condylar cartilage showed significant degenerative changes, with disorganized collagen fibers and reduced proteoglycan synthesis on the cartilage surface. IL-1α and MMP-3 were expressed in the intracellular and extracellular matrix of the condylar cartilage, and their expression levels were increased (P<0.01). After 2 weeks of stress removal, the serum levels of CORT and ACTH were decreased but higher than control group (P<0.01), and behavioral changes were still different from the control group (P<0.01); the loosened collagen fibers could still be seen on the surface of condylar cartilage, and some free cell areas were visible within the proliferative layer; additionally, IL-1α and MMP-3 expression in the condyle was reduced in all layers of cartilage when compared with the stress group, but was still higher than in the control group (P<0.01). After 4 weeks of stress removal, the serum levels of CORT and ACTH changes returned to normal levels and behavioral changes were still different from control group (P<0.05); a few collagen fibers could be seen on the surface of the condylar cartilage and the expressions of IL-1α and MMP-3 decreased significantly compared with the stress group (P<0.01), with the similar level of IL-1α (P>0.05) and higher expression of MMP-3 comparing with the control group (P<0.01). After 8 weeks of stress removal, behavioral changes returned to normal levels, with no statistically significant differences compared with the control group (P>0.05). The condylar collagen fibers increased and showed a corrugated pattern, and no serious subchondral bone damage as well as irreversible damage occurred. Both of the expression levels of IL-1α and MMP-3 approached those of the control group after 8 weeks of stress removal (P>0.05). @*Conclusion@# The behavioral changes and condylar cartilage damage caused by CUMS could be self-repaired. The decline in IL-1α and MMP-3 expression may be one of the intrinsic mechanisms of this self-repair process.

A study on the biological effects of electromagnetic pulse with different high⁃intensity on condylar cartilage in rats / 口腔疾病防治

Objective@#To explore the biological effects of electromagnetic pulse (EMP) with different high intensities on condylar cartilage in rats. @*Methods@#SD rats were randomly divided into a sham group (Sham) and an irradiation group (EMP1: 500 kV/m, 10 Hz; EMP2: 270 kV/m, 10 Hz). Then, they were sacrificed at 1 h, 3 h, 12 h, 24 h and 3 d after irradiation. The degree of cartilage degeneration was evaluated by HE, safranine O-fast green, type Ⅱ collagen immunohistochemistry and TUNEL staining. Immunohistochemistry and western blot were performed to detect the expression of the matrix degradation factors: matrix metalloproteinase-13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-5) and the apoptosis key factor cleaved-cysteinyl aspartate specific proteinase (cleaved-Caspase3) in condylar cartilage. @*Results @#HE staining showed that, compared with the Sham group, a small amount of exfoliation was found on the fibrous surface layer of the cartilage after irradiation in the EMP1 and EMP2 groups. Compared with the Sham group, the percentage of safranine O-fast green-positive area decreased significantly at 12 h and 24 h (both P<0.01) in the EMP1 group and 12 h and 24 h in the EMP2 group (both P<0.05); the percentage of type Ⅱ collagen-positive area decreased significantly at 3 h and 12 h (P<0.05, P<0.001) in the EMP1 group. In addition, the number of TUNEL-positive apoptotic cells increased significantly at 1 h, 3 h, 12 h, and 24 h in the EMP1 group and 1 h, 3 h, and 12 h in the EMP2 group (P<0.05). Moreover, at different timepoints (except at 3 d) in the EMP1 group and EMP2 group, the percentage of MMP-13, ADAMTS-5- and cleaved Caspase3-positive chondrocytes and their protein levels in condylar cartilage increased significantly after irradiation (P<0.05). @* Conclusion@# EMP with a certain degree of high-intensity can induce early transient damage to condylar cartilage. This effect is dose-and time-dependent.

Efficacy of osteochondral fragment fixation using bioabsorbable pins for Hepple Ⅱ osteochondral lesions of the talus in adolescents / 国际外科学杂志

Objective:To investigate the efficacy of osteochondral fragment fixation using bioabsorbable pins for Hepple Ⅱ osteochondral lesions of the talus (OLT) in adolescents.Methods:Retrospective case analysis was used. The clinical data and follow-up results of 13 adolescent patients (13 feet) with Hepple Ⅱ OLT were all treated with osteochondral fragment fixation using bioabsorbable pins admitted to Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2017 to December 2021 were retrospectively analyzed. There were 7 males and 6 females, with 13 right feet. The age was (14.85±2.23) years old, ranged from 12 to 18 years old. According to the American orthopedic foot and ankle society (AOFAS) ankle-hindfoot score, visual analogue scale (VAS) and SF-36 score before operation and at the last follow-up were used to evaluate the efficacy and function of the patients. Measurement data with normal distribution were represented as mean ± standard deviation( ± s), and the comparison between groups was conducted using the t-test; The mearsurement data with skewness distribution were expressed by M( Q1, Q3), and rank-sum test was used for inter-group comparison. Results:Thirteen adolescent patients (13 feet) with Hepple Ⅱ OLT underwent surgery successfully and were followed up for (25.54±9.95) months. All wounds healed by first intention, and no complications such as wound infection and delayed healing occurred. Preoperative AOFAS ankle-posterior foot score, VAS and SF-36 score were 58.62±3.55, 7.00 (6.50, 8.00) and 68.38±4.81, respectively. At the last follow-up, the scores were 97.38±2.73, 1.00 (0.00, 1.00), 91.15±4.28, respectively, and the results were significantly improved at the last follow-up, with the difference between the two groups statistically significant( P<0.05). Conclusion:Osteochondral fragment fixation using bioabsorbable pins which can promote cartilage repair, significantly improve symptoms, and achieve better clinical satisfaction with fewer complications, is a safe and effective surgical treatment option for Hepple Ⅱ OLT in adolescents with satisfactory short-term clinical outcomes.

Stress Relaxation Behavior of Collagen Type II- Silk Fibroin Composite Cartilage Scaffold under Different Degradation Cycles / 医用生物力学

Objective To study stress relaxation behaviors of cartilage scaffolds under different degradation cycles by using finite element analysis combined with theoretical models. Methods Based on the established degradation theoretical model, the elastic modulus of the scaffold was calculated under different degradation cycles. The finite element model of cartilage scaffolds was established and stress relaxation simulation was performed to analyze the variation of scaffold relaxation stress with time. The stress relaxation constitutive model was established to predict mechanical properties of the scaffold. Results The elastic modulus of cartilage scaffolds at 14 th, 28th, 42nd, 56th day after degradation was 32. 35, 31. 12, 29. 91, 28. 74 kPa, respectively. The upper layer for cartilage scaffolds was the largest. The overall relaxation stress of the scaffold decreased rapidly with time and then tended to be stable. At 8th week after degradation, the stress which the scaffold couldwithstand was still within the physiological load range of the cartilage. The predicted results of the stress relaxation constitutive model were in good agreement with the finite element simulation results. Conclusions The elastic modulus of the scaffold gradually decreases with the increase of degradation time. The longer the degradation period is, the less stress the scaffold can withstand. At the same degradation period, the larger the applied compressive strain, the larger the stress on the scaffold. Both the finite element simulation and stress relaxation constitutive model can effectively predict stress variations of cartilage scaffolds under degradation

Analysis of Knee Joint Stress During Drop Jump Landing in Females with Generalised Joint Hypermobility / 医用生物力学

Objective To analyze the differences of von Mises stress distribution in knee cartilage and meniscus in female with generalised joint hypermobility (GJH) and healthy female during drop jump landing. Methods The kinematic and ground reaction force (GRF) characteristics of knee joint in female with GJH and healthy female at the moment of peak vertical GRF (VGRF) during loading phase of drop jump landing were collected. The knee joint reaction force was calculated via inverse dynamics, and the combined force of knee joint along long axis of the femur was applied as the load. Based on three-dimensional (3D) finite element model of a female knee joint, numerical simulations were performed separately during drop jump landing of subjects in two groups, and von Mises stresses and stress distribution of knee cartilage and meniscus were calculated. Results At the moment of peak VGRF during drop jump landing, knee flexion and valgus angles in GJH group and control group showed a statistical significance (P<0. 05). Compared with control group, knee flexion angle decreased and valgus angle increased in GJH group. During drop jump landing, GJH group bore larger stress inside the knee joint, and stress distribution in weight-bearing areas of the medial and lateral tibiofemoral compartments was uneven, while the lateral femoral cartilage lateral condyle, the anterior and middle lateral of lateral tibial cartilage, the anterior angle and body lateral margin of lateral meniscus were stress concentration sites. Conclusions For females with GJH, the stability of knee joint decreases and force lines change in jumping events, due to the increased range of motion of knee joint and relaxation of joint capsule, which increases the risk of cartilage and meniscal injury in lateral knee joint. During jumping sports, females with GJH should especially prevent knee joint injury caused by altered force lines in frontal plane of knee joint.

Research Progress on Biomechanics and Mechanobiology of Articular Cartilage in 2022 / 医用生物力学

As a kind of elastic load-bearing connective tissues on bone surface in dynamic joints, articular cartilage can provide low wear lubrication, shock absorption, load transfer and other supporting functions, and has hierarchical fiber composite structures and excellent mechanical properties. As an avascular and aneural tissue,the degenerated articular cartilage lacks the capability of self-healing after damage. The high incidence of arthritisis still a hot spot in basic and clinical researches. Articular cartilage is a mechanical sensitive tissue, andmechanical environment will affect the development of tissues in different directions. Extensive researches onbiomechanics and mechanobiology of articular cartilage were conducted in 2022. Many studies on morphology, function and mechanical state of cartilage,as well as mechanical state of cartilage under different conditions were reported. Some cartilage-related loading devices were designed at animal, tissue and cell levels. Researches onthe repair of cartilage degeneration and injury under mechanical loads were carried out in vitro and in vivo, andsome important repair method and means were obtained. The biomechanical and mechanobiology research on articular cartilage is the basis of arthritis, cartilage defect and repair. The influence of quantitative mechanical under 4 conditions on the repair of articular cartilage injury needs further study in vivo and in vitro