An Injectable Hydrogel Scaffold With Kartogenin-Encapsulated Nanoparticles for Porcine Cartilage Regeneration: A 12-Month Follow-up Study

Background: Treatment of cartilage lesions is clinically challenging. A previous study demonstrated that a hyaluronic acid hydrogel ( m-HA) with kartogenin (KGN)-loaded PLGA nanoparticles ( m-HA+KGN treatment) achieved superior cartilage repair in a rabbit model. However, large animals serve as a bridge to translate animal outcomes into the clinic. Hypotheses: (1) m-HA+KGN treatment could facilitate hyaline cartilage and subchondral bone tissue repair in a porcine model. (2) Defect size and type (full-thickness chondral vs osteochondral) influence the therapeutic efficacy of m-HA+KGN treatment. Study Design: Controlled laboratory study. Methods: 48 minipigs were randomized into 3 treatment groups: m-HA hydrogel with KGN-loaded PLGA nanoparticles ( m-HA+KGN treatment), m-HA hydrogel ( m-HA treatment), and untreated (blank treatment). Full-thickness chondral (6.5 mm or 8.5 mm in diameter) or osteochondral (6.5 mm or 8.5 mm in diameter; 5-mm depth) defects were prepared in the medial femoral condyle. At 6 and 12 months postoperatively, defect repair was assessed by macroscopic appearance, magnetic resonance imaging (MRI), micro–computed tomography (µCT), and histologic and biomechanical tests. Results: The m-HA+KGN group exhibited superior gross and histological healing after evaluation at 6 and 12 months postoperatively. Improved quality of the repaired cartilage demonstrated by MRI and better subchondral bone reconstruction assessed by µCT were observed in the m-HA+KGN group. The m-HA+KGN group showed more hyaline-like cartilage exhibited by histological staining in terms of extracellular matrix, cartilage lacuna, and type II collagen. The biomechanical properties were improved in the m-HA+KGN group. With m-HA+KGN treatment, defects with a diameter of 6.5 mm or full-thickness chondral-type defects possessed significantly higher ICRS macroscopic and histological scores compared with diameter 8.5 mm or osteochondral-type defects. Conclusion: (1) m-HA+KGN treatment facilitated hyaline cartilage and subchondral bone tissue repair in a porcine model at the 12-month follow-up. (2) m-HA+KGN treatment demonstrated better therapeutic efficacy in defects with a diameter of 6.5 mm or full-thickness chondral-type defects. Clinical Relevance: This study verified the efficacy of this innovative KGN release system on cartilage repair. The KGN release system can be injected into defect sites arthroscopically. This convenient and minimally invasive operation holds important prospects for clinical application.

THE ANATOMY OF STRUCTURES OF THE KNEE JOINT AT DEFORMING ARTHROSIS ACCORDING TO THE DATA OF VITAL AND POST-VITAL STUDIES

In the anatomical part of the study on 50 non-embalmed and 50 polymer-embalmed anatomical preparations of the knee joint of an adult were studied the degenerative-dystrophic changes in the bone and auxiliary elements of the knee joint with deforming arthrosis of the I and III stage. The objects of the clinical part of the study were patients with degenerative-dystrophic changes in the knee joint of varying severity who underwent x-ray examination (150 people), magnetic resonance imaging (60 people), diagnostic arthroscopy (35 people). For determine the stage of gonarthrosis in patients, the classification of N.S. Kosinskaya (1961) was used. Identified in the study of anatomical preparations of the knee joint with I stage of gonarthrosis degenerative-dystrophic changes were present in all patients with a similar severity of arthrosis of the knee joint and were confirmed by the results of their additional examination. It study is shown that for the diagnosis of degenerative meniscus ruptures and degenerative changes in the cruciate ligaments of the knee joint, the most informative method is magnetic resonance imaging, and diagnostic arthroscopy does not provide an exhaustive diagnosis of these manifestations. The performed comparison of vital and post-vital morphological manifestations of I stage gonarthrosis, as well as an analysis of the effectiveness of the applied diagnostic techniques convincingly indicates the need for this category of patients to perform x-ray studies and magnetic resonance imaging of the knee joint. When performing magnetic resonance imaging of the knee joint with III stage gonarthrosis trabecular edema of varying severity was found, localized mainly in the subchondral bone tissue of the internal condyles of the tibia and femur, and signs of avascular necrosis of the condyle of the condyle were revealed. The analysis of the intravital diagnostic methods used in patients with III stage gonarthrosis and comparing their results with the data of anatomical studies of knee joint preparations with the same stage of the degenerative-dystrophic process, indicated sufficient visualization capabilities of each from presented methods for additional examination.

The Effect of Low Intensity Pulsed Ultrasound on Proliferation of Rat Condylar Cartilage Cells in Hypoxia Culture

Temporomandibular disorder (TMD) is a common and frequently-occurring oral and maxillofacial disease. Restoration of the joint's cartilage and subchondral bone tissue is the key to treat TMD. Low intensity pulsed ultrasound (LIPUS) has been proved to be effective in facilitating chondrocyte's proliferation, which inspired us to probe its treatment effect on TMD. With an isolated and hypoxic cultured mandibular condylar chondrocytes (MCC), we established a model for TMD. HIF-1α and VEGF's mRNA level was increased in hypoxic cultured MCC, which indicates our model simulated the cell's status caused by TMD pathology. When stimulated with LIIPUS at 45 mW/cm2, the MCC's apoptosis rate was inhibited and its proliferation was improved with best efficiency. Further experiment revealed that LIPUS restored MCC's Metalloproteinase's (MMP) up-regulation and collagen II's downregulation in hypoxic cultured MCC, respectively, which might be related to LIPUS's improvement effect on MCC.

Efficiency of Tranexamic Acid in Management of Surgical Orthopedic Bleeding in Patients with Haemophilia

Haemophilia is an inherited bleeding disorder (gonosomala recessive, related to chromosome X, with transmission from carrying women to male descendents) characterised from the clinic point of view by important bleeding, secondary to some minimum and biologic traumas by deficiency of trombo-plastino-formation, consecutive to either a deficit of factor VIII (haemophilia A), or the factor IX (haemophilia B). The most characteristic manifestation of hemophilia is intra-articular � hemarthrosis. Its repetitive character leads to irreversible lesions of the articular structures, inducing lesions of the synovium with degenerative effects over the articular cartilage and destructive effects for the subchondral bone tissue. In time, these lesions require orthopaedic surgery to improve the locomotor activity. Managing an efficient hemostasis is vital during surgery, due to high risk of bleeding triggered by coagulopathy and surgery. Numerous studies carried out underlined the efficiency of the tranexamic acid (TXA) in reducing bleeding, in different surgery branches, by inhibiting the enzymatic degradation of fibrin. In orthopaedic surgery, the tranexamic acid is frequently used in case of hip and knee arthroplasties, reducing the bleeding and blood transfusion necessary to the treatment of posthaemorrhagic anemia. This paper wants to assess the efficiency of the tranexamic acid in realization of hemostasis to another category of patients, haemophiliac patients with indication of total hip and knee endoprosthesis.