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Background: Primary synovial chondromatosis (PSC) is a rare idiopathic pathology characterized by the formation of osseocartilaginous nodules within synovial joints, tendons, or bursae. The mineralization pattern of PSC nodules is poorly understood and has yet to be investigated using elemental analysis. Mapping this pattern could elucidate the progression of the disease. Materials and methods: PSC nodules discovered during dissection of a formalin fixed donor were analyzed. Scanning electron microscopy paired with energy dispersive X-ray spectroscopy (SEM-EDS) was used to quantify calcium and phosphorus levels to distinguish mineralized components from cartilage, indicated by increased carbon and oxygen concentrations. Results: Nine nodules with average dimensions 1.76cm x 1.25cm were identified in the semimembranosus bursa. SEM-EDS demonstrated increased calcium phosphate levels in nodular cores, while outer margins contained primarily carbon and oxygen. Quantification of these elements revealed nodular peripheries to contain 68.0% carbon, 30.2% oxygen, 0.8% calcium, and 1.0% phosphate, while cores were comprised of 38.1% carbon, 42.1% oxygen, 14.1% calcium, and 5.7% phosphate. Conclusions: Nodules were found to have mineralized cores embedded within a cartilaginous matrix. This pattern suggests disease progression is facilitated by endochondral ossification, opening the potential for new therapeutic techniques.

ObjectivesTo investigate the role of endogenous TSG-6 in human osteoarthritis (OA) and assess the disease-modifying potential of a TSG-6-based biological treatment in cell, explant and animal models of OA.MethodsKnee articular cartilages from OA patients were analysed for TSG-6 protein and mRNA expression using immunohistochemistry and RNAscope, respectively. The inhibitory activities of TSG-6 and its isolated Link module domain (Link_TSG6) on cytokine-induced glycosaminoglycan loss in OA cartilage explants were compared. Mesenchymal stem/stromal cell (MSC)-derived chondrocyte pellet cultures were used to determine the effects of Link_TSG6 and full-length TSG-6 on IL-1α-, IL-1β- or TNF-stimulated ADAMTS4, ADAMTS5 and MMP13 mRNA expression. Link_TSG6 was administered i.a. to the rat ACLTpMMx model and cartilage damage and tactile allodynia were assayed.ResultsTSG-6 is predominantly associated with chondrocytes in regions of cartilage damage and its expression is negatively correlated with MMP13, the major collagenase implicated in OA progression. Link_TSG6 is more potent than full-length TSG-6 at dose-dependently inhibiting cytokine-mediated matrix breakdown in human OA cartilage explants; about 50% of donor cartilages, from 59 tested, were responsive to Link_TSG6 treatment. Similarly, Link_TSG6 displayed more potent effects in 3D pellet cultures, suppressing aggrecanase and collagenase gene expression. Link_TSG6 treatment reduced touch-evoked pain and dose-dependently inhibited cartilage damage in a rodent model of surgically-induced OA.ConclusionsNative TSG-6 is associated with a low catabolic chondrocyte phenotype in OA cartilage. Link_TSG6, which has enhanced chondroprotective activity compared to the full-length TSG-6 protein, demonstrates potential as a disease modifying OA drug (DMOAD) and warrants further investigation and development.KEY MESSAGESWhat is already known about this subject?TSG-6, a protein with anti-inflammatory and protective effects in other tissues, is expressed in joints affected by osteoarthritis – a condition for which there are no disease-modifying drugs.What does this study add?A novel protective mechanism has been identified, whereby TSG-6 inhibits inflammatory cytokine-induced catabolic pathways in cartilage.The Link module of TSG-6 (Link_TSG6) has been shown to have greater potency than TSG-6 as an inhibitor of cartilage damage and is efficacious in a rat model of osteoarthritis.Data from cartilage explants indicate that OA patients can be stratified for Link_TSG6 responsiveness.How might this impact on clinical practice or future developments?Link_TSG6 has been identified as potential disease-modifying OA drug that mimics an intrinsic protective process.

Posterior ankle impingement syndrome is mainly seen in ballet dancers and frequently associated with specific movements in ballet such as pointe and demi pointe in which the whole-body weight is applied to the maximally plantar flexed ankle. We performed arthroscopic debridement for 2 dedicated ballet dancers on the intervening soft tissue causing posterior ankle impingement syndrome (PAIS). In both cases, T2-weighted magnetic resonance imaging (MRI) revealed low-signal intensity of meniscus-like soft tissue without abnormal osseous findings, connecting from the posterior side of the talus to Kager's fat pad. To examine the intervening soft tissue in detail, we performed histological evaluation by hematoxylin and eosin staining, Safranin O fast green staining, and immunohistochemistry for type I collagen and type II collagen. Hematoxylin and eosin staining showed that there was cartilage-like tissue including chondrocyte-like cells in contact with fibrous tissue. The extracellular matrix in the cartilage zone was consistently stained by Safranin O staining and type II collagen without any staining with type I collagen. These findings suggested that the meniscus-like soft tissue appearing as low-signal intensity on MRI at the posterior side of talus included hyaline-like cartilage. To the extent of our knowledge, these were rare cases of hyaline-like cartilage generation causing PAIS in ballet dancers, which might be associated with ballet specific movements resulting in chondrogenesis.

Purpose The purpose of this study was to determine whether radiographic parameters, intraoperative findings, patient-reported outcome measures, or intraoperative interventions that were performed differentiate those patients with >2 mm of joint space who convert under two years to total hip arthroplasty (THA) after undergoing hip arthroscopy for femoroacetabular impingement (FAI) when compared to those converting after 2 years. Methods Included in this study were patients who underwent conversion to THA within 2 years of primary hip arthroscopy from a prospectively collected patient registry from 2007 to 2017. Patients who underwent early conversions to arthroplasty were matched 1:1 with patients who converted after 2 years, based upon age and gender. Preoperative outcome scores were collected, including Short Form-12, modified Harris Hip Score, and Hip Outcome Score. Additionally, variables from the preoperative radiographic evaluation, surgical findings, and procedures performed were also compared. Results Forty-nine patients were included in the early conversion group and were matched with 49 patients in the later conversion group. Patients with lateral center edge angles of less than 25° were more likely to be in the early failure group [OR: 3.9; 95% CI: 1.01 to 15]. Patients with unipolar chondral defects on either the femoral (P = .128) or acetabular side (P = .656) were not at increased odds for early conversion compared to later conversion; however, those with bipolar chondral lesions at the time of surgery had increased odds of early conversions [OR: 3.3; 95% CI: 1.4 to 8] (P = .01). Neither surgical treatment nor preoperative patient-reported outcome measures were associated with early conversion. Conclusions In patient with >2 mm of joint space, lateral center edge angles of less than 25° and those with bipolar articular cartilage lesions seen at the time of hip arthroscopy are at increased risk for conversion to total hip arthroplasty within two years. Level of Evidence Level III, retrospective comparison study.

Summary Objective Osteoarthritis (OA) pathogenesis involves the interaction of articular cartilage with surrounding tissues, which are innervated by tyrosine hydroxylase-positive (TH+) sympathetic nerve fibers suggesting a role of the sympathetic nervous system (SNS) during OA progression. We analyzed the effects of sympathectomy (Syx) in a murine OA model. Methods Peripheral Syx was generated by 6-hydroxydopamine (6-OHDA) injections in male C57BL/6 mice. OA was induced in wild-type (WT) and Syx mice by destabilization of the medial meniscus (DMM). TH+ fibers and splenic NE were analyzed to evaluate Syx efficiency. OA progression was examined by OARSI and synovitis scores and micro-CT. Expression of TH, α2A- and β2-adrenergic receptors (AR), and activity of osteoblasts (ALP) and osteoclasts (TRAP) was investigated by stainings. Results Syx resulted in synovial TH+ fiber elimination and splenic NE decrease. Cartilage degradation and synovitis after DMM were comparably progressive in both WT and Syx mice. Calcified cartilage (CC) and subchondral bone plate (SCBP) thickness and bone volume fraction (BV/TV) increased in Syx mice due to increased ALP and decreased TRAP activities compared to WT 8 weeks after DMMWT and Syx mice developed osteophytes and meniscal ossicles without any differences between the groups. AR numbers decreased in cartilage but increased in synovium and osteophyte regions after DMM in both WT and Syx mice. Conclusion Peripheral dampening of SNS activity aggravated OA-specific cartilage calcification and subchondral bone thickening but did not influence cartilage degradation and synovitis. Therefore, SNS might be an attractive target for the development of novel therapeutic strategies for pathologies of the subchondral bone.

Osteoarthritis (OA) is the most common degenerative disease in older adults and its treatment remains unsatisfactory. This study aimed to evaluate the effectiveness and explore the therapeutic mechanisms of the combination of platelet-rich plasma (PRP) and ozone (O3) for knee OA.Thirty male rabbits were randomly divided into five groups (Control group, OA group, PRP group, O3 group, and PRP + O3 group). Rabbit model of OA were induced by improved Hulth surgery. Gross articular observation, histopathological examination and cartilage scoring system were used to assess the articular cartilage destruction. The bone morphogenetic protein-2 (BMP-2) mRNA expression in joint fluid was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The expression of type II collagen, matrix metalloproteinase-1 (MMP-1) of cartilage was detected via Immunohistochemistry. Pain behavior was observed by percent ipsilateral weight-bearing (PIW) asymmetry.The content of platelet in PRP was increased by 6.2-times that in whole blood. Among induced OA groups (the OA, PRP, O3 and PRP + O3 group), PRP + O3 significantly inhibited the surgically induced increase in gross articular alterations, histopathological damage of cartilage and Mankin score when compared to the OA, PRP and O3 groups (P0.05). Observed pain behavior by weight-bearing asymmetry, in the PRP + O3 group was reversed at 3 and 6 weeks after the administration of PRP + O3 (PIW asymmetry: -10.66%±1.172%). In addition, surgery-induced BMP-2 mRNA expression was significantly downregulated after the treatment of PRP, O3 and PRP + O3 (P0.01). PRP + O3 group significantly increased the expression of type II collagen but decreased MMP-1 of cartilage in comparison to OA, PRP and O3 groups (P0.05) by immunohistochemical analysis.PRP combined with O3 may prevent cartilage destruction and improve weight-bearing asymmetry by restoring homeostasis between anabolism and catabolism of extracellular matrix in progressive OA. Furthermore, a combination of PRP and O3 might achieve even better results than the two agents alone.

Summary Objective Although cartilage degeneration and invasion of the subchondral bone plate in entheseal lesion has been considered to consequently lead bony ankylosis in ankylosing spondylitis (AS), no evident mechanisms are known. Design To identify histopathological and physiological changes in enthesitis-related ankylosis in AS, we performed molecular characterization of transcription factors and surface markers, and transcriptome analysis with human tissues. Entheseal tissue containing subchondral bone was obtained from the facet joints of 9 patients with AS and 10 disease controls, and assessed by using differential staining techniques. Enthesis cells were isolated, characterized, stimulated with TNF and/or IL-17A, and analysed by cell-based experimental tools. Results We found diffusely distributed granular tissue and cartilage in the subchondral bone in AS. Co-expression of SOX9, a specific transcription factor in cartilage, and matrix metalloproteinase 13 (MMP13) was found in the granular tissues within the subchondral bone from AS patients. Intriguingly, SOX9 expression was significantly higher in AS enthesis cells than controls and correlated with TNFR1 and IL-17RA expressions, which is important for high reactivity to TNF and IL-17A cytokines. Co-stimulation by TNF and IL-17A resulted in accelerated mineralization/calcification features, and increased OCN expression in AS enthesis cells. Furthermore, SOX9 overexpression in enthesis leads to promoting mineralization feature by TNF and IL-17A stimuli. Finally, OCN expression is elevated in the destructive enthesis of advanced AS. Conclusion These findings provide insight into the links between inflammation and the mineralization of entheseal tissue as the initiation of spinal ankylosis, emphasizing the importance of SOX9+ enthesis cells.

Orthoregeneration is defined as a solution for orthopaedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and, optimally, provide an environment for tissue regeneration. Options include drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electromagnetic stimuli. The goal of regenerative medicine is to enhance the healing of tissue after musculoskeletal injuries as both isolated treatment and adjunct to surgical management, using novel therapies to improve recovery and outcomes. Various orthopaedic biologics (orthobiologics) have been investigated for the treatment of pathology involving the hip, including osteonecrosis (aseptic necrosis) involving bone marrow, bone, and cartilage, and chondral injuries involving articular cartilage, synovium, and bone marrow. Promising and established treatment modalities for osteonecrosis include nonweightbearing; pharmacological treatments including low molecular-weight heparin, prostacyclin, statins, bisphosphonates, and denosumab, a receptor activator of nuclear factor-kB ligand inhibitor; extracorporeal shock wave therapy; pulsed electromagnetic fields; core decompression surgery; cellular therapies including bone marrow aspirate comprising mesenchymal stromal cells (MSCs aka mesenchymal stem cells) and bone marrow autologous concentrate, with or without expanded or cultured cells, and possible addition of bone morphogenetic protein-2, vascular endothelial growth factor, and basic fibroblast growth factor; and arterial perfusion of MSCs that may be combined with addition of carriers or scaffolds including autologous MSCs cultured with beta-tricalcium phosphate ceramics associated with a free vascularized fibula. Promising and established treatment modalities for chondral lesions include autologous platelet-rich plasma; hyaluronic acid; MSCs (in expanded or nonexpanded form) derived from bone marrow or other sources such as fat, placenta, umbilical cord blood, synovial membrane, and cartilage; microfracture or microfracture augmented with membrane containing MSCs, collagen, HA, or synthetic polymer; mosaicplasty; 1-stage autologous cartilage translation (ACT) or 2-stage ACT using 3-dimensional spheroids; and autologous cartilage grafting; chondral flap repair, or flap fixation with fibrin glue. Hip pain is catastrophic in young patients, and promising therapies offer an alternative to premature arthroplasty. This may address both physical and psychological components of pain; the goal is to avoid or postpone an artificial joint. Level of Evidence Level V, expert opinion.

Osteoarthritis (OA) is the most prevalent type of arthritis worldwide, resulting in pain and often chronic disability and a significant burden on healthcare systems globally. Non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, intra-articular corticosteroid injections are of little value in the long term, and opioids may have ominous consequences. Radiotherapy of knee OA has no added value. Physical therapy, exercises, weight loss, and lifestyle modifications may give pain relief, improve physical functioning and quality of life. However, none of them has articular cartilage regenerating potential. Due to a better understanding of osteoarthritis, innovative new treatment options have been developed. In this narrative review, we focus on emerging OA knee treatments, relieving symptoms, and regenerating damaged articular cartilage that includes intra-articular human serum albumin, conventional disease-modifying anti-rheumatic drugs (DMARDs), metformin, lipid-lowering agents (statin), nerve growth factors antagonists, bone morphogenetic protein, fibroblast growth factors, Platelet-Rich Plasma (PRP), Mesenchymal Stem Cells (MSC), exosomes, interleukin-1 blockers, gene-based therapy, and bisphosphonate.

Background Osteochondritis dissecans (OCD) is considered to show the following stages of pathological progression: IA, nearly normal-cartilaginous; IB, deteriorated-cartilaginous; IIA, cartilage-ossifying; and IIB, cartilage-osteonecrotic. However, the validity of this pathological staging for OCD has yet to be confirmed in a large number of cases. Purpose The aim of the present study was to confirm the clinical validity of the proposed pathological staging of OCD. Methods The subjects were 74 patients (mean age, 14.2 years; mean skeletal age score, 25.6 points) with capitellar OCD. Partially detached articular fragments were surgically removed, and were examined histologically. The articular fragments were independently assessed by five observers and the reliability of assessment was examined. The correlation between the pathological stages and the clinical data was analyzed. Results The reliability of the assessment among five observers was almost perfect. OCD stages of IA, IB, IIA, and IIB were evident in eight, 36, 10, and 20 patients, respectively. OCD-I (cartilaginous) and OCD-II (osteochondral) corresponded significantly to radiographic stage I (radiolucency) and stage II (delayed ossification), respectively. The pathological OCD stages were significantly correlated with the clinical data, including the period from symptom onset to surgery, patient age, and the skeletal age score (p Conclusion Our results confirmed that the proposed pathological staging of OCD corresponds to the observed clinical progression of OCD, thus validating the staging system. Our findings revealed that OCD begins with separation beneath the epiphyseal cartilage which is programmed to be replaced with bone. When a stage IA articular fragment has remained partially detached for a prolonged period, the epiphyseal cartilage may be deteriorated and become degenerated, and subsequent ossification may not occur, as is evident in OCD-IB. In contrast, stage IA with a vascular supply through the fibrocartilaginous connection can progress to stage IIA. During the prolonged period in which the osteochondral articular fragment remains un-united, microtrauma can cause to disturb the blood supply to the bony fragment, resulting in osteonecrosis (stage IIB).

Post-traumatic OA (PTOA) arises from joint injury, it accounts for a significant portion of patients with osteoarthritis. Intra-articular fractures associated with hemarthrosis, ruptures and rough damage to the meniscus, ligaments, cartilage injuries are the most common causes of PTOA. Damage to articular cartilage can occur in the period immediately after the injury, in the near future or develop several years after the injury. Even with appropriate treatment, such as rigid fixation of intra-articular fractures, reconstruction of damaged ligament with a successful restoration of joint biomechanics, the risk of PTOA ranges from 20 to more than 50 %. In the last decade, the role of inflammation in the development and progression of PTOA is being actively discussed and studied. Signs of inflammation may be observed in the joint fluid and tissues of patients with injuries of the joints and the risk of post-traumatic osteoarthritis. In addition, inflammatory mechanisms lead to the risk of developing osteoarthritis and its progression after injury. The development of PTOA involves molecular and cellular mechanisms. Synovium, articular cartilage and subchondral bone also react to the injury by changing metabolic activity and expression of inflammatory proteins. This review summarizes the results of recent studies of pathological mechanisms underlying PTOA development. This allows you to take a new look at the mechanisms of PTOA development, the role of inflammation in the progression of the disease, and to assess the limitations for early pharmacological intervention., Посттравматический остеоартрит (ПТОА) возникает при травме суставов, на его долю приходится значительная часть пациентов с остеоартритом (ОА). Внутрисуставные переломы, сопровождающиеся гемартрозом, разрывы и грубые повреждения менисков, связочного аппарата, травмы хрящевой ткани являются наиболее частыми причинами, ведущими к ПТОА. Повреждение суставного хряща может происходить в период сразу после травмы, в ближайшее время или развиваться через несколько лет после травмы. Даже при соответствующем лечении, таком, как жесткая фиксация внутрисуставных переломов, реконструкция поврежденных связок с успешным восстановлением биомеханики сустава, риск развития ПТОА колеблется от 20 до более чем 50 %. В последнее десятилетие активно обсуждается и изучается роль воспаления в развитии и прогрессировании ПТОА. Признаки воспаления можно наблюдать в суставных жидкостях и тканях у пациентов с травмой суставов и риском развития посттравматического остеоартрита. Кроме того, воспалительные механизмы способствуют риску развития остеоартрита и прогрессированию его после травмы. В развитии ПТОА задействованы молекулярные и клеточные механизмы. Синовиальная оболочка, суставной хрящ и субхондральная кость также реагируют на травму изменением метаболической активности и экспрессии провоспалительных белков. Данный обзор суммирует результаты недавних исследований патологических механизмов, лежащих в основе развития ПТОА. Это позволяет по-новому взглянуть на механизмы развития ПТОА, роль воспаления в прогрессировании болезни, а также оценить потенциальные возможности для раннего фармакологического вмешательства., Посттравматичний остеоартрит (ПТОА) виникає при травмі суглобів, на його частку припадає значна частина пацієнтів з остеоартритом (ОА). Внутрішньосуглобові переломи, що супроводжуються гемартрозом, розриви і грубі ушкодження менісків, зв’язкового апарату, травми хрящової тканини є найбільш частими причинами, що призводять до ПТОА. Пошкодження суглобового хряща може відбуватися в період відразу після травми, найближчим часом або розвиватися через кілька років після травми. Навіть при відповідному лікуванні, такому, як жорстка фіксація внутрішньосуглобових переломів, реконструкція пошкоджених зв’язок з успішним відновленням біомеханіки суглоба, ризик розвитку ПТОА коливається від 20 до більш ніж 50 %. Останнім десятиліттям активно обговорюється і вивчається роль запалення в розвитку і прогресуванні ПТОА. Ознаки запалення можна спостерігати в суглобових рідинах і тканинах у пацієнтів із травмою суглобів і ризиком розвитку посттравматичного остеоартриту. Крім того, запальні механізми сприяють ризику розвитку остеоартриту і прогресуванню його після травми. У розвитку ПТОА задіяні молекулярні і клітинні механізми. Синовіальна оболонка, суглобовий хрящ і субхондральна кістка також реагують на травму зміною метаболічної активності та експресії прозапальних білків. Даний огляд підсумовує результати недавніх досліджень патологічних механізмів, що лежать в основі розвитку ПТОА. Це дозволяє по-новому поглянути на механізми розвитку ПТОА, роль запалення в прогресуванні хвороби, а також оцінити потенційні можливості для раннього фармакологічного втручання.

The aim of the work was to evaluate the clinical and pathogenetic links of osteoarthritis (OA) with the qualitative composition of the drinking water in zones of patients’ residence. Material and Methods. The observation included 133 patients with primary OA aged 58.90 ± 0.83 years. In 33 urban and rural regions we have assessed levels of hardness and salinity of drinking water, concentration of chlorides, sulfates in it, phosphates and nitrates, content of toxic trace elements (Ba, Li, Ni, Pb). Results. Poor quality of drinking water in the regions where people live lead to the development of OA at a younger age, which subsequently determines the cumulative severity of articular syndrome, the nature of bone-destructive changes in the joints (osteoporosis, bone erosion, cartilage flaps), the formation of symptomatic reactive synovitis (chloride and nitrates concentration), the rate of disease progression, the emergence of intraarticular calcification deposits, osteophytosis and epiphyseal osteoporosis (degree of water salinity and hardness). The severity of OA and the rate of progression of bone-destructive changes in the joints depend on the level of trace elements, which determine the prevalence of joint syndrome, the development of Heberden’s and Bouchard’s nodes, spondylopathy, degree of reactive synovitis, osteoporosis, subchondral sclerosis, ligamentosis, intraarticular cartilage flaps and Hoffa’s bodies, and high content of Pb is a risk factor for unfavorable course of the disease. Conclusions. There were identified certain clinical and pathogenetic correlation of OA and the qualitative composition of drinking water in the regions where people live., Целью работы стала оценка клинико-патогенетических связей остеоартроза (ОА) с качественным составом питьевой воды в зонах проживания больных. Материал и методы. Под наблюдением находились 133 больных первичным ОA в возрасте 58,90 ± 0,83 года. Оценивали в 33 городских и сельских регионах уровни жесткости и минерализации питьевой воды, концентрации в ней хлоридов, сульфатов, фосфатов и нитратов, содержание токсичных микроэлементов (Ba, Li, Ni, Pb). Результаты. Низкое качество питьевой воды в регионах проживания людей способствует развитию ОА в более молодом возрасте, что в последующем определяет интегральную тяжесть артикулярного синдрома, характер костно-деструктивных изменений в суставах (развитие остеопороза, остеоузур, хондромных тел), формирование манифестного реактивного синовита (концентрации хлоридов и нитратов), темпы прогрессирования заболевания, появление внутрисуставных отложений кальцинатов, остеофитоза и эпифизарного остеопороза (степень минерализации и жесткости воды). Тяжесть ОА и темпы прогрессирования костно-деструктивных изменений со стороны суставов зависят от уровня микроэлементов, которые определяют распространенность суставного синдрома, развитие узелков Гебердена и/или Бушара, спондилопатии, степень реактивного синовита, остеопороза, субхондрального склероза, лигаментоза, интраартикулярных хондромных тел и тел Гоффа, а высокое содержание Pb является фактором риска неблагоприятного течения заболевания. Выводы: выявлены определенные клинико-патогенетические связи ОА с качественным составом питьевой воды в регионах проживания больных., Метою роботи стала оцінка клініко-патогенетичних зв’язків остеоартрозу (ОА) з якісним складом питної води в зонах проживання хворих. Матеріал і методи. Під спостереженням перебували 133 хворі на первинний ОA віком 58,90 ± 0,83 року. Оцінювали в 33 міських і сільських регіонах рівні жорсткості й мінералізації питної води, концентрації в ній хлоридів, сульфатів, фосфатів і нітратів, вміст токсичних мікроелементів (Ba, Li, Ni, Pb). Результати. Низька якість питної води в регіонах проживання людей сприяє розвитку ОА в молодшому віці, що в подальшому визначає інтегральну тяжкість артикулярного синдрому, характер кістково-деструктивних змін у суглобах (розвиток остеопорозу, остеоузур, хондромних тіл), формування маніфестного реактивного синовіту (концентрації хлоридів і нітратів), темпи прогресування захворювання, появу внутрішньосуглобових відкладень кальцинатів, остеофітозу й епіфізарного остеопорозу (ступінь мінералізації та жорсткості води). Тяжкість ОА і темпи прогресування кістково-деструктивних змін з боку суглобів залежать від рівня мікроелементів, які визначають поширеність суглобового синдрому, розвиток вузликів Гебердена та/або Бушара, спондилопатії, ступінь реактивного синовіту, остеопорозу, субхондрального склерозу, лігаментозу, інтраартикулярних хондромних тіл та тіл Гоффа, а високий вміст Pb є чинником ризику несприятливого перебігу захворювання. Висновки: виявлені певні клініко-патогенетичні зв’язки ОА з якісним складом питної води в регіонах проживання хворих.

Objective: Based on the expression changes in the TGF-β/ALK5/Smad2/3 signal transduction pathway, the repair of cartilage injury in the rabbit knee joint was investigated and evaluated by oral administration of naringin in combination with acellular dermal matrix implantation. Methods: First, twenty New Zealand white rabbits were randomly divided into five groups: a sham operation group (Sham group), a model group (Mod group), a naringin group (Nar group), an acellular dermal matrix group (ADM group), a naringin ​+ ​acellular dermal matrix group (Nar/ADM group). After the 12th week, the repaired tissues were assessed for histomorphology and repair content of the repaired site by observing the morphological characteristics of articular cartilage. The International Cartilage Repair Society (ICRS)'s macroscopic evaluation of the cartilage repair scale and the quantitative scoring repair effect of the modified O'Driscoll grading system were used as evaluation criteria. In addition, the structure of the rabbit knee joint was evaluated by micro-CT scan, histological staining (H & E staining, Alcian blue staining, Safranin-O staining) and immunohistochemical staining (TGF-β2 immunostaining, TGF-β3 immunostaining, Sox-9 immunostaining). Results: ① The observation of the repair morphology of joint defect tissues showed that the repair effects of the Nar and ADM groups were better than that of the Mod group, and the repair effect of Nar/ADM group was the best (P

BACKGROUND CONTEXT Low back pain is one of the most common musculoskeletal disorders. Although, the pathology of intervertebral disc (IVD) degeneration has been modeled using various biological methods, these models are inadequate for simulating similar pathologic states in humans. PURPOSE This study investigated whether monosodium iodoacetate (MIA) injection into the IVD of rats could generate a reliable model of IVD degeneration. STUDY DESIGN/SETTINGS In vivo animal study. METHODS MIA was injected into two-disc spaces (L4-5 and L5-6) of Sprague–Dawley rats. Their behaviors were examined by measuring weight load shifts from hind to forefoot, rearing, and von Frey tests. We examined the inhibition of pain behavior through intraperitoneal morphine injection and measured cyclooxygenase-2 (COX-2) and transcription factor nuclear factor-kappa B (NF-κB) levels in the IVD and dorsal root ganglion (DRG) by Western blot. Bone alterations were assessed by microfocus computed tomography (micro-CT), and IVD and/or cartilage changes were evaluated by hematoxylin and eosin and safranin-O staining and inducible nitric oxide synthase (iNOS) immunohistochemistry. The other authors declare no conflicts of interest. This project funded by the Memorial Fund and the National Research Foundation of Korea (NRF). RESULTS We observed increased weight load shifts to the forefoot and decreased rearing. Morphine-injected rats showed reduced pain. NF-κB and COX-2 expression increased in the IVD and left and/or right DRG. Micro-CT analyses suggested progressive bone deformation. Histologic examination showed decreased IVD width and nucleus pulposus area. Cartilaginous changes indicated epiphyseal growth plate loss. Finally, iNOS expression was increased in the subchondral endplate. CONCLUSIONS These results suggest that low back pain (LBP) models can be developed by MIA injection into the IVDs of rats and that an animal model is useful for exploring degenerative alterations in the affected discs. Therefore, MIA injection may be a useful model for the study of changes in the IVD to elucidate the mechanisms underlying clinical symptoms, such as LBP, in patients with IVD degeneration. CLINICAL SIGNIFICANCE This model in which MIA was injected into the disc better represented the human histologic and behavioral characteristics than the existing puncture model.

Polyvinyl alcohol hydrogel synthetic cartilage implants are increasingly used to treat advanced Freiberg disease. We report a case with recurrence of symptoms within 6 weeks and required revision for fracture of the implant. We describe a revision technique with modified osteochondral bone graft to deal with the variables of revision surgery namely: the bone loss, collateral ligament insufficiency, and changes to the proximal phalanx articular surface. We describe a postoperative plan, recovery and a good outcome achieved in 12 month follow-up.

Graphical abstract, Highlights • Established a new experimental rat model of the developmental trochlear dysplasia; • Using the macroscopic morphological and micro-CT to assess trochlear dysplasia; • Using Histological staining to investigate the cartilage degradation of the model; • Investigated the relationship of the PI3K/AKT signaling pathway with trochlear dysplasia cartilage degeneration; • Using immunohistochemistry and qPCR to investigate the PI3K/AKT and the marker of the cartilage degeneration., Introduction Trochlear dysplasia is a commonly encountered lower extremity deformity in humans. However, the molecular mechanism of cartilage degeneration in trochlear dysplasia is unclear thus far. Objectives The PI3K/AKT signaling pathway is known to be important for regulating the pathophysiology of cartilage degeneration. The aim of this study was to investigate the relationship of the PI3K/AKT signaling pathway with trochlear dysplasia cartilage degeneration. Methods In total, 120 female Sprague-Dawley rats (4 weeks of age) were randomly separated into control and experimental groups. Distal femurs were isolated from the experimental group at 4, 8, and 12 weeks after surgery; they were isolated from the control group at the same time points. Micro-computed tomography and histological examination were performed to investigate trochlear anatomy and changes in trochlear cartilage. Subsequently, expression patterns of PI3K/AKT, TGFβ1, and ADAMTS-4 in cartilage were investigated by immunohistochemistry and quantitative polymerase chain reaction. Results In the experimental group, the trochlear dysplasia model was successfully established at 8 weeks after surgery. Moreover, cartilage degeneration was observed beginning at 8 weeks after surgery, with higher protein and mRNA expression levels of PI3K/AKT, TGFβ1, and ADAMTS-4, relative to the control group. Conclusion Patellar instability might lead to trochlear dysplasia in growing rats. Moreover, trochlear dysplasia may cause patellofemoral osteoarthritis; cartilage degeneration in trochlear dysplasia might be associated with activation of the PI3K/AKT signaling pathway. These results provide insights regarding the high incidence of osteoarthritis in patients with trochlear dysplasia. However, more research is needed to clarify the underlying mechanisms.

Summary Background With the experience-based hypothesis of low donor site morbidity (DSM) for free flaps from the distal femur, this cohort study aimed to evaluate the DSM according to objective and reproducible criteria. Methods One hundred and fifty-six patients who had a flap harvest from either the medial or lateral femoral condyle region between 2005 and 2017 were included. A retrospective chart review was performed for all patients. In total, 97 patients were available for a follow-up examination. Outcomes were assessed according to objective (Knee Society Score; Larson Knee Score; OAK Score; 0–100 points), patient-reported (IKDC Score; KOOS Score; 0–100 points), and radiologic criteria (Kellgren and Lawrence Score; MRI Osteoarthritis Knee Score). Results The median follow-up time was 1,529 days (range: 248–4,810). The mean Knee Society Score (94.8 ± 10.1), Larson Knee Score (94.5 ± 10.1), and OAK Score (95.5 ± 6.6) showed nearly unimpaired knee function. The overall patient-reported DSM was low (IKDC Score: 86.7 ± 17.4; KOOS Score: 89.3 ± 17.1). Osteochondral (OC) flaps had a significantly higher DSM, regardless of the donor site. Bone flaps did not show any relevant radiologic morbidity in the Kellgren and Lawrence Score. Besides the procedure-associated cartilage lesions at the OC donor sites, MRI Osteoarthritis Knee Score did not show any significant presence of further knee pathologies in the bilateral MRI Scans. The obvious cartilage lesions did not have a relevant impact on the knee function of most patients. Conclusion The DSM for bone and soft-tissue flaps from the femoral condyle region is negligible. OC flaps are associated with a significantly higher DSM, although a clinically relevant impact on knee function was not evident in the majority of patients.

Aging is one of the primary factors influencing development of osteoarthritis, and the TGF-β pathway plays an important role in age-related osteoarthritis. Specifically, GDF15 phosphorylates SMAD2/3 in the TGF-β pathway to inhibit cardiomyocyte hypertrophy, and promote proliferation of chondrocytes. However, age-dependent changes in the level of GDF15 are unclear, as is whether GDF15 phosphorylates SMAD2/3 in the TGF-β pathway to promote proliferation of old chondrocytes. This study, therefore, sought to examine the effect of various GDF15 concentrations on old chondrocyte proliferation.Serum and cartilage specimens of young adults and older adults were collected, and GDF15 expression was quantified. Human chondrocytes were then cultured following routine protocols, and different concentrations of recombinant human GDF15 or pSMAD2 inhibitor were added into the culture medium. After 48 h of culturing, the proliferation of chondrocytes was detected by EdU, and the expression MMP13, SMAD2, and pSMAD2 was detected in chondrocytes via western blot and qRT-PCR analysis.The GDF15 content in serum and cartilage of young adults was higher than that of older adults (p 0.05). The number of EdU-positive cells in the experimental group (containing recombinant human GDF15) was higher than that in the control group (medium only) (p 0.05). Compared with the control group, chondrocytes in the experimental group showed increased pSMAD2 and type II collagen content (p 0.05) and decreased MMP13 (p 0.05), with no significant difference in SMAD2 content (p 0.05). Moreover, no significant differences were observed between the control group and the TGF-β signaling inhibitor group. The gene expression level of each index was consistent with the protein expression level.The GDF15 content of serum and cartilage in young adults is higher than in older adults, and GDF15 functions to promote the proliferation of chondrocytes by phosphorylating SMAD2 in older individuals.

Osteoarthritis (OA) is characterized by the gradual loss of cartilage. Sprifermin, a recombinant FGF18, is being developed as a cartilage anabolic drug. PRO-C2 is a serum marker of type II collagen formation and low levels have been shown to be prognostic of radiographic progression. The aim of the study was to investigate whether the patient groups with either high or low PRO-C2 levels responded differently to sprifermin.PRO-C2 was measured in synovial fluid (SF) (n = 59) and serum samples (n = 225) from participants of the FORWARD study, a 2-year phase IIb clinical trial testing the efficacy of intra-articular (IA) sprifermin over placebo. The difference between sprifermin and placebo in respect to in change cartilage thickness (measured by quantitative (q) MRI) was analyzed in groups with either high or low (3SF levels of PRO-C2 increased over time in response to sprifermin, but not to placebo. In the placebo arm, significantly (p = 0.005) more cartilage was lost in the low vs high PRO-C2 group over the 2-year period. The contrast between sprifermin and placebo was significant (p 0.001), ranging from 0.104 mm at week 26 to 0.229 mm at week 104 in the low PRO-C2 group. This result was not significant in the high PRO-C2 group ranging from -0.034 to 0.142.Patients with low serum PRO-C2 levels lost more cartilage thickness over time and grew more cartilage in response to sprifermin vs a placebo when compared to patients with high PRO-C2 levels.

The main indication for medial Unicondylar Knee Arthroplasty (UKA) is Full-Thickness Cartilage Loss (FTCL) in the isolated medial compartment of the knee. However, controversial outcomes were reported in patients with Partial-Thickness Cartilage Loss (PTCL). The aim of this study is to compare PTCL and FTCL based on intraoperative findings in medial UKA in terms of functional outcomes and complication rates requiring reoperation and revision.Two hundred and fifteen knees of 174 patients who underwent mobile-bearing UKA between October 2014 and February 2018 for the diagnosis of symptomatic anteromedial osteoarthritis were evaluated retrospectively. A single senior surgeon evaluated the type of cartilage loss in the medial compartment intraoperatively according to the International Cartilage Repair Society classification system. Clinical outcomes were evaluated using Oxford Knee Score (OKS) and International Knee Documentation Committee (IKDC) score pre- and post-operatively at the last follow-up. Patients with PTCL and FTCL were compared in terms of their pre- and post-operative OKS and IKDC scores, and their improvements, as well as complication rates requiring reoperation and revision.The mean follow-up time was 33.1 ± 5.3 months. The PTCL (n = 80) and FTCL (n = 135) groups were statistically similar in terms of age (P = 0.41), gender (P = 0.921), body mass index (P = 0.165), bilaterality (P = 0.111), American Society of Anesthesiologists physical status (P = 0.218), Charlson Comorbidity Index (P = 0.74), and post-operative follow-up (P = 0.167). The mean pre-operative OKS and IKDC scores were improved from 24.5 ± 4.1 and 39.9 ± 5 to 40.3 ± 3.6 and 73.9 ± 7.7 at the last follow-up, respectively (P0.001). Pre-operative OKS and IKDC scores were superior in favor of the PTCL group. However, no significant difference was found between the groups in terms of post-operative OKS (P = 0.53) and IKDC (P = 0.975) scores, and their improvements (OKS, P = 0.953; IKDC, P = 0.536). The complication rates requiring reoperation was 5% (n = 11) in all patients. Of these, 9% (n = 7) from the PTCL group and 3% (n = 4) from the FTCL group were reoperated. Nevertheless, no significant difference was found between the groups (P = 0.105).In PTCL, medial UKA is a reliable surgery in terms of functional outcomes, the same as in FTCL; however, its complication rates requiring reoperation is higher without statistical significance.Level III, Therapeutic Study.

Objective Mechanical and biologic cues drive cellular signaling in cartilage development, health, and disease. Primary cilia proteins, which are implicated in the transduction of biologic and physiochemical signals, control cartilage formation during skeletal development. This study was undertaken to assess the influence of the ciliary protein intraflagellar transport protein 88 (IFT88) on postnatal cartilage from mice with conditional knockout of the Ift88 gene (Ift88-KO). Methods Ift88fl/fl and aggrecanCreERT2 mice were crossed to create a strain of cartilage-specific Ift88-KO mice (aggrecanCreERT2;Ift88fl/fl). In these Ift88-KO mice and Ift88fl/fl control mice, tibial articular cartilage thickness was assessed by histomorphometry, and the integrity of the cartilage was assessed using Osteoarthritis Research Society International (OARSI) damage scores, from adolescence through adulthood. In situ mechanisms of cartilage damage were investigated in the microdissected cartilage sections using immunohistochemistry, RNAScope analysis, and quantitative polymerase chain reaction. Osteoarthritis (OA) was induced in aggrecanCreERT2;Ift88fl/fl mice and Ift88fl/fl control mice using surgical destabilization of the medial meniscus (DMM). Following tamoxifen injection and DMM surgery, the mice were given free access to exercise on a wheel. Results Deletion of Ift88 resulted in progressive reduction in the thickness of the medial tibial cartilage in adolescent mice, as well as marked atrophy of the cartilage in mice during adulthood. In aggrecanCreERT2;Ift88fl/fl mice at age 34 weeks, the median thickness of the medial tibial cartilage was 89.42 μm (95% confidence interval [95% CI] 84.00–93.49), whereas in Ift88fl/fl controls at the same age, the median cartilage thickness was 104.00 μm (95% CI 100.30–110.50; P Conclusion Our results in a mouse model of OA demonstrate that IFT88 performs a chondroprotective role in articular cartilage by controlling the calcification of cartilage via maintenance of a threshold of Hh signaling during physiologic loading.

Purpose Several factors present at the time of posterior cruciate ligament reconstruction (PCLR) may cause the subsequent progression of articular cartilage lesions. This study aimed to evaluate postsurgical articular cartilage lesions which can be seen on MRI in patients who underwent arthroscopic PCLR with or without concomitant meniscal pathology. Material and methods A total of sixty-five patients (mean age 35.8 ± 12.3 years) who underwent arthroscopic PCLR were included in this retrospective study. Patients were divided into two groups: ten patients with concomitant meniscal injuries at the time of PCLR who underwent meniscal surgery and fifty-five patients with intact menisci. The cartilage status of all knees was evaluated by MRI and modified Noyes classification. Results Cartilage lesions were observed in 18 patients (27.7%) on the last follow-up MRI. The cartilage lesions were more common in the medial (15.4%) and patellofemoral (12.3%) compartments than in the lateral compartment (7.7%). Progression of cartilage lesions was present in 11 patients (16.9%) during follow-up MRI. The majority of cartilage lesions with progression were located in the medial compartment. The meniscal pathology group showed a higher prevalence of articular cartilage lesions on the last follow-up MRI (21.8% versus 60%, p = 0.022). In multivariate Cox regression, concomitant meniscal pathology was significantly associated with progression of articular cartilage lesions (p = 0.044). Conclusion PCLR patients with associated meniscal pathology showed worse cartilage condition and more progression of cartilage lesions than isolated PCLR patients. Attention to this risk factor might provide more applicable treatment options for potential osteoarthritis prevention strategies.

Background We evaluated the risk factors for pain catastrophizing, kinesiophobia, and elevated depressive symptoms among patients undergoing high-grade cartilage defect surgery. We hypothesized that cartilage patients would demonstrate high scores on pain catastrophizing, kinesiophobia, and depression testing prior to surgery. Methods Two hundred and ten patients undergoing surgery for high-grade cartilage defects (56% chondroplasty, 36% microfracture, 22% autologous chondrocyte implantation) completed a preoperative survey before undergoing surgery. Outcome scores assessed were: International Knee Documentation Committee-Symptom (IKDC-S) score, Tegner activity score, Pain catastrophizing scale (PCS), Tampa scale for kinesiophobia (TSK-11), and Patient Health Questionnaire depression scale (PHQ-9). Multivariate logistic regression was used to determine what pre-operative factors predicted pain catastrophizing, kinesiophobia, and elevated depressive symptoms. Results The mean pre-operative Tegner score was 5.8 (SD 2.4) and IKDC-S score was 44.7 (SD 11.1). Prior to surgery, 19% had abnormal pain catastrophizing (PCS ≥ 20 points), 14.4% had moderate-severe depression (PHQ ≥ 10), and 49.0% had high kinesiophobia (TSK-11 ≥ 25). Lower pre-operative Tegner scores predicted moderate-severe depressive symptoms (per point decrease, OR 1.36, 95% CI 1.06, 1.76; p = 0.008). Predictors of elevated pain catastrophizing were lower pre-operative IKDC-S scores (per 5-point decrease, OR 1.28, 95% CI 1.08, 1.51; p = 0.002) and symptom duration >6 months (OR 2.20 CI 1.14, 4.32; p = 0.02). A lower pre-operative IKDC-S score (per 5-point decrease, OR 1.17, CI 1.03, 1.33; p = 0.02) predicted elevated kinesiophobia. Conclusion Low self-reported function, low activity level and symptom duration greater than six months are associated with poor preoperative psychological status.

Objective The purpose of this study is to systematically review the literature and to evaluate the outcomes following bone marrow stimulation (BMS) for nonprimary osteochondral lesions of the talus (OLT). Design A literature search was performed to identify studies published using PubMed (MEDLINE), EMBASE, CDSR, DARE, and CENTRAL. The review was performed according to the PRISMA guidelines. Two authors separately and independently screened the search results and conducted the quality assessment using the Methodological Index for Non-Randomized Studies (MINORS). Studies were pooled on clinical, sports, work, and imaging outcomes, as well as revision rates and complications. The primary outcome was clinical success rate. Results Five studies with 70 patients were included in whom nonprimary OLTs were treated with secondary BMS. The pooled clinical success rate was 61% (95% confidence interval [CI], 50-72). The rate of return to any level of sport was 83% (95% CI, 70-91), while the return to pre-injury level of sport was 55% (95% CI, 34-74). The rate of return to work was 92% (95% CI, 78-97), and the complication rate was assessed to be 10% (95% CI, 4-22). Imaging outcomes were heterogeneous in outcome assessment, though a depressed subchondral bone plate was observed in 91% of the patients. The revision rate was 27% (95% CI, 18-40). Conclusions The overall success rate of arthroscopic BMS for nonprimary osteochondral lesions of the talus was 61%, including a revision rate of 27%. Return to sports, work, and complication outcomes yielded fair to good results.

Background and purpose of the study Arthroscopic debridement, the most commonly applied surgical technique for focal cartilage lesions in the knee, is not included in most treatment algorithms because of discouraging results in the management of osteoarthritis of the knee. The present systematic review evaluates the outcome of arthroscopic cartilage debridement as the primary treatment of focal knee chondral lesions in adults, and defines its indications and role as the primary treatment of focal knee chondral lesions. Methods Two independent investigators searched PubMed, Cochrane CENTRAL, and Virtual Health Library databases using the terms “knee”, “cartilage”, “chondral”, “lesions”, “injury”, “damage”, “debridement”, “chondroplasty”, “chondrectomy”, alone and in combination. Clinical studies evaluating the effect of mechanical cartilage debridement in adults with symptomatic focal cartilage lesions in the knee joint regardless of the defect size and depth were included. We excluded studies if patients had a concomitant ligament or meniscus injury, and/or had additional debridement with monopolar radiofrequency energy. Main findings Available studies suggest good to excellent short and medium-term functional outcomes (KOOS, LKSS, Tegner scale) for focal cartilage lesions treated with debridement regardless of the defect size and depth. Data are lacking comparing cartilage debridement versus other cartilage repair techniques. Conclusions Arthroscopic debridement of focal articular cartilage lesions of the knee is associated with good to excellent short and medium-term postoperative outcomes, especially in terms of functional improvement. Arthroscopic debridement may be considered in the primary treatment of focal cartilage injuries regardless of the defect size and depth. However, available studies are limited and the level of evidence is low.

Chondrosarcomas are heterogeneous matrix-producing cartilaginous neoplasms with variable clinical behavior. Subtypes include conventional (75%), dedifferentiated (10%), clear cell (2%), mesenchymal (2%), and periosteal chondrosarcoma (

Objective Intraarticular (IA) administration of platelet-rich plasma (PRP) has been proposed as a new strategy to halt osteoarthritis (OA) progression. In patients with severe OA, its potential is limited because it is unable to reach the subchondral bone, so a new strategy is needed, and intraosseous (IO) infiltration has been suggested. The purpose is to assess the impact of IA together with IO infiltration of plasma rich in growth factors (PRGF) in serum hyaluronic acid (HA) and type II collagen cleavage neoepitope (C2C) levels. Design A total of 32 rabbits were included in the study and randomly divided into 2 groups: control and treatment. A 4-mm chondral defect was created in the medial femoral condyle and IA followed by IO infiltration were performed. Serum C2C and HA levels were measured using enzyme-linked immunosorbent assay (ELISA) tests before infiltration and 28, 56, and 84 days post-infiltration. Results Significant lower C2C serum levels were obtained in treatment group (IA + IO infiltration of PRGF) at 84 days post-infiltration than in control group (IA infiltration of PRGF + IO infiltration of saline solution), while no significant differences between groups were reported at any other study times. Regarding HA, at 56 days post-infiltration, greater significant levels were seen in the treatment group. However, at 84 days post-infiltration, no significant differences were obtained, although lower levels were reported in the treatment group. Conclusions Despite inconclusive, the results suggest that the combination of IA and IO infiltration with PRGF may enhance cartilage and subchondral bone regeneration, but further studies are needed.

Florid reactive periostitis ossificans (FRPO) is a benign juxta-cortical lesion of unknown etiology which most commonly occurs in the hands and feet. We report the radiographic, CT, and MR features of a pathologically confirmed FRPO in the distal femur, a location in which only a handful of cases has been reported. A 26-year-old male who presented with distal thigh pain initially underwent radiograph and CT, which illustrated a well-circumscribed, ossified lesion associated with the cortex of the femur without contiguity with the medullary canal. A subsequent MRI demonstrated heterogeneous signal intensity corresponding to the ossified portion of the lesion with a T2 hyperintense cartilaginous cap and surrounding edema. The lesion was surgically excised and pathologic diagnosis of FRPO, a mixture of osteoid, mature bone, cartilage and fibrous tissue, with associated inflammatory cells, was confirmed. Follow up four months after surgery revealed significant improvement in the patient's pain.

After harvesting multiple costal cartilages, the local defect disrupts the integrity of the chest wall and may lead to obvious thoracic complications, such as local depression and asymmetry of the bilateral thoracic height. Decellularized materials have been used for tissue reconstruction in clinical surgeries. To apply xenogenic decellularized cartilage in costal cartilage defects, porcine-derived auricular and costal cartilage was tested for characterization, cytotoxicity, macrophage response, and tissue regeneration. Most of the DNA and α-Gal were effectively removed, and the collagen was well preserved after the decellularization process. The glycosaminoglycan (GAG) content decreased significantly compared to that in untreated cartilage. The decellularized auricular cartilage had a larger pore size, more pores, and a higher degradation rate than the decellularized costal cartilage. No apparent nuclei or structural damage was observed in the extracellular matrix. The decellularized auricular cartilage had a higher cell proliferation rate and more prominent immunomodulatory effect than the other groups. Two types of decellularized cartilage, particularly decellularized auricular cartilage, promoted the tissue regeneration in the cartilage defect area, combined with noticeable cartilage morphology and increased chondrogenic gene expression. In our research, the functional components and structure of the extracellular matrix were well preserved after the decellularization process. The decellularized cartilage had better biocompatibility and suitable microenvironment for tissue regeneration in the defect area, suggesting its potential application in cartilage repair during the surgery. Statement of significance Autologous costal cartilage has been widely used in various surgeries, while the cartilage defects after the harvesting of multiple costal cartilages may cause localized chest wall deformities. Decellularized cartilage is an ideal material that could be produced in the factory and applied in surgeries. In this study, both decellularized costal cartilage and auricular cartilage preserved original structure, functional biocompatibility, immunosuppressive effects, and promoted tissue regeneration in the cartilage defect area.

Although uncommon in many pathology practices, cartilage-forming tumors represent some of the most frequent primary bone tumors. Diagnosis can be challenging given their variable histologic spectrum and the presence of overlapping morphologic, immunohistochemical, and genetic features between benign and malignant entities, particularly low-grade malignancies. Correlation with clinical findings and radiographic features is crucial for achieving an accurate diagnosis and appropriate clinical management, ranging from observation to excision. Tumors can be characterized broadly by their location in relation to the bone (surface or intramedullary). In specific instances, ancillary testing may help.

Objectives To compare the prevalence of pre- and postoperative osseous deformities and intra-articular lesions in patients with persistent pain following arthroscopic femoroacetabular impingement (FAI) correction and to identify imaging findings associated with progressive cartilage damage. Methods Retrospective study evaluating patients with hip pain following arthroscopic FAI correction between 2010 and 2018. Pre- and postoperative imaging studies were analyzed independently by two blinded readers for osseous deformities (cam-deformity, hip dysplasia, acetabular overcoverage, femoral torsion) and intra-articular lesions (chondro-labral damage, capsular lesions). Prevalence of osseous deformities and intra-articular lesions was compared with paired t-tests/McNemar tests for continuous/dichotomous data. Association between imaging findings and progressive cartilage damage was assessed with logistic regression. Results Forty-six patients (mean age 29 ± 10 years; 30 female) were included. Postoperatively, 74% (34/46) of patients had any osseous deformity including 48% (22/46) acetabular and femoral deformities. Ninety-six percent (44/46) had an intra-articular lesion ranging from 20% (9/46) for femoral to 65% (30/46) for acetabular cartilage lesions. Prevalence of hip dysplasia increased (2 to 20%, p = 0.01) from pre- to postoperatively while prevalence of cam-deformity decreased (83 to 28%, p Progressive cartilage damage was detected in 37% (17/46) of patients and was associated with extensive preoperative cartilage damage > 2 h, i.e., > 60° (OR 7.72; p = 0.02) and an incremental increase in postoperative alpha angles (OR 1.18; p = 0.04). Conclusion Prevalence of osseous deformities secondary to over- or undercorrrection was high. Extensive preoperative cartilage damage and higher postoperative alpha angles increase the risk for progressive degeneration. Key Points • The majority of patients presented with osseous deformities of the acetabulum or femur (74%) and with intra-articular lesions (96%) on postoperative imaging. • Prevalence of hip dysplasia increased (2 to 20%, p = 0.01) from pre- to postoperatively while prevalence of a cam deformity decreased (83 to 28%, p • Progressive cartilage damage was present in 37% of patients and was associated with extensive preoperative cartilage damage > 2 h (OR 7.72; p = 0.02) and with an incremental increase in postoperative alpha angles (OR 1.18; p = 0.04).

Zusammenfassung Operationsziel Offene Therapie osteochondraler Läsionen des Kniegelenks zur vollständigen Auffüllung knöcherner Defekte und Wiederherstellung der Gelenkfläche. Indikationen Fokale, symptomatische osteochondrale Defekte des Kniegelenks ab einer Knochendefekttiefe von ≥ 5 mm und Größe von ≥ 1,5 cm2. Kontraindikationen Arthrose (> KL Grad 2), „kissing lesions“ (ICRS > Grad 2), Alter > 50 Jahre, unbehandelte Bandinstabilitäten oder Beinachsenfehstellungen zum Nachteil des betroffenen Gelenkkompartiments, fehlendes Defektcontainment, entzündliche Gelenkerkrankungen. Operationstechnik Zweizeitiger Eingriff: Ersteingriff (arthroskopische Knorpelprobenentnahme): Defektevaluierung, Entnahme von Knorpelstücken für die Chondrozytenkultivierung, bei Bedarf Behandlung von Begleitpathologien. Zweiteingriff (offene Defektbehandlung): Arthrotomie, Präparation des knöchernen Defekts, Auffüllung mit autologen Spongiosazylindern aus dem Beckenkamm, Knorpeldefektpräparation (kann größer als knöcherner Defekt sein) und matrixgestützte autologe Chondrozytentransplantation. Weiterbehandlung Ersteingriff: frühfunktionelle Nachbehandlung mit schmerzorientierter Vollbelastung je nach Begleiteingriffen. Zweiteingriff: keine Drainage, funktionelle Kniegelenkorthese in Streckstellung für 1 Woche, danach schrittweise Freigabe der Flexion, Teilbelastung für 6 Wochen, Motorschiene (CPM) ab dem 1. postoperativen Tag. Ergebnisse Seit 2018 sind 8 Patienten (mittleres Alter 29,4 Jahre, Spanne 18 bis 36) mit der beschriebenen Technik behandelt worden. Alle Patienten konnten nach durchschnittlich 12 Monaten nachuntersucht werden. Der Gesamt-KOOS (Knee injury and Osteoarthritis Outcome Score) verbesserte sich im Mittel von 45,8 auf 81,3, und die postoperativen radiologischen Kontrollen zeigten die Einheilung der Spongiosazylinder bei allen Patienten. Der MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) Score ergab 80,4 Punkte.

OBJECTIVE To investigate the expression and clinical significance of serum soluble AXL in patients with radiographic knee osteoarthritis (KOA). METHODS There were 183 patients with KOA who were selected and divided based on the Kellgren-Lawrence (KL) score into KL 0 subgroups (n = 42), KL I-II subgroups (n = 90), and KL III-IV subgroups (n = 51). Healthy volunteers (n = 170) in our hospital were selected with matched age and gender as the control group. AXL level in serum was detected by enzyme-linked immunosorbent assay. The correlation between serum AXL with severity and clinical indicators of osteoarthritis was analyzed. RESULTS The level of serum AXL was significantly higher in the osteoarthritis group than that in the control group (P

Every fifth inhabitant of the earth has been diagnosed with osteoarthritis of various etiologies. Morphological studies of arthritis provide a theoretical basis for creating optimal treatments for this pathology. Given the polyetiological nature of the disease, the choice of the optimal experimental model, which would be as close as possible to the real conditions of inflammatory process reproduction, is the topical issue. The purpose of the study was to confirm the pathological reaction of the joint tissues of laboratory animals in response to intraperitoneal administration of ƛ-carrageenan. The study was performed on 50 white Wistar rats males aged 12 weeks, weighing 130-150 g. The animals were euthanized by an overdose of anaesthesia according to the terms of the study (1 - 30 days). Fragments of the distal metaepiphyses of the femur and proximal metaepiphyses of the tibia were used for histological examination. Staining of sections obtained on the microtome was performed with haematoxylin, eosin, and Van Gieson`s stain. From the first day of the experimental study, a corresponding reaction of the joint tissues was being observed. Particularly pronounced were the changes in the synovial membrane in the form of oedema of the villi accompanied by an increased filling of blood vessels with foci of thrombosis. Gradually, up to 5 days in the synovial membrane, proliferative changes took place with a clear definition of the multilineage of the integumentary layer, vascular reaction with a tendency to thrombosis, in some places necrosis of synoviocytes was observed, but relative integrity of the morphological structure was still provided by protective barriers of bone and cartilage. On the 7th day pronounced resorption of both bone and cartilage tissue occurred, tissue structure became disorganized and functional layer became thin, accompanied by massive intracellular lysis. The process of synoviocytes necrobiosis with fatty degeneration spread. The histological picture of 10 days is characterized by generalized destruction of bone beams; the destroyed cartilage was replaced by granulation tissue with the presence of cavities. Massive foci of lymphocytic infiltration were observed in the synovial membrane. On the 14th day, a fragmentation of cartilage happened, most of the bone beams (trabeculae) were destroyed. After 3 weeks the morphological picture of cartilage tissue was determined by the appearance in the lacunae of viable cells, the number of which was close to normal. Bone beams were restored, although they remained thin. In a synovial membrane, the hyperplasia of apical departments of villi, leukocytes infiltration, disorganization of connective tissue, and separate vascular disturbances remained. 30 days of the experiment were characterized by a relative recovery of structural relationships to normal. The obtained data confirm the feasibility of using carrageenan in experimental studies of osteoarthritis.

Osteoarthritis is a joint disease that causes degeneration of articular cartilage and involvement of subcutaneous bone and inflammation of surrounding tissues. It can affect any joints, but the most common joints are the joints of the hands, feet, knees, thighs, and spine. Osteoarthritis patients need surgery in acute cases. The use of methods that increase the efficiency of this surgery has always been considered by researchers and surgeons. For this purpose, in the current study, the effect of synthesized cartilage tissue from human adipose-derived mesenchymal stem cells was considered in orthopedic spine surgery in patients with osteoarthritis. Thirty patients over the age of 60 who had acute spinal osteoarthritis and required surgery were selected. The pellet culture system of human adipose-derive mesenchymal stem cells of each patient was used to construct cartilage tissue. For 15 of them, in addition to implants, cartilage grafts were transplanted during surgery. All patients were monitored by the Oswestry Disability Index questionnaire, for one year. In general, the results showed that over time, patients with transplanted cartilage tissue and implants were in a better condition than patients who underwent only implant surgery.

BACKGROUND Diced cartilage glue (DG) grafts have been widely used in dorsal augmentation but can induce dorsal irregularities. The authors evaluated the postoperative feasibility of a crushed septal cartilage-covered diced cartilage glue (CCDG) graft. METHODS The medical records of 38 patients who underwent dorsal augmentation rhinoplasty with an open approach were retrospectively reviewed. DG graft was used in 18 patients (47.4%), and CCDG graft was used in 20 patients (52.6%). Surgical outcomes were assessed by comparing anthropometric data on facial photographs and satisfaction questionnaires on aesthetic outcomes and palpable irregularities on nasal dorsum before and after surgery. RESULTS Both groups showed successful aesthetic outcomes. Dorsal height, radix height, and tip projection were all increased postoperatively in both groups. Tip rotation did not significantly increase (p > 0.05). Both groups showed similar outcomes in terms of aesthetic satisfaction but a significant difference in palpable irregularity. CCDG graft group showed significantly better (p = 0.04) satisfaction with dorsal irregularities (4.15 ± 0.75) than the DG graft group (3.56 ± 0.92). CCDG graft group also showed significantly better mean values (p = 0.048) in the degree of irregularity by two surgeons (3.85 ± 0.65) than the DG graft group (3.25 ± 0.97). No patient had significant complaints about irregular dorsum, and none of them underwent a revision rhinoplasty. CONCLUSION CCDG graft can be a complementary option for avoiding postoperative irregular dorsum complications. LEVEL OF EVIDENCE IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A 17-year-old student athlete suffering from stress-related knee pain asked for help. MRI revealed an unstable osteochondral lesion. Because of time pressure due to the patient’s academic exams and his schedule as a basketball player, an autologous chondrocyte transplantation (ACT) as the standard surgical treatment plan was not accepted by the patient. This was mainly because of its two-step character three weeks in between surgeries. Therefore, a surgical one-step therapy option as alternative treatment to ACT was needed. The patient received simultaneous autologous cancellous bone grafting and minced cartilage procedure in a sandwich technique. After successful rehabilitation, the patient continued his studies of sports science and his active career as a basketball player successfully. Several different procedures are used for the treatment of cartilage defects. The following factors play a significant role: defect size, location, patient age, and sports ambitions. In the case described here, ACT would have been the conventional, but not the ideal option in the perspective of this individual patient because of the two-step surgery and the longer rehabilitation time. Therefore, the minced cartilage method presented a valid alternative, even though long-term data are still missing and prospective studies comparing this procedure with others are needed in the future.

Background: Autologous osteochondral transplantation (AOT) using a cylindrical graft in the treatment of osteochondral lesions of the talus (OLTs) is typically indicated for patients with larger lesions. However, with lesions that are irregular in shape, the AOT graft may not completely replace the lesion. For these lesions, we utilize extracellular matrix cartilage allograft (EMCA) augmentation in AOT to act as a physiologic grout at the host-graft interface. Purpose: To determine if the combination of EMCA with concentrated bone marrow aspirate (CBMA) would improve integration of the host-graft interface and subsequently reduce postoperative cyst formation after AOT. It was also hypothesized that EMCA in conjunction with CBMA would demonstrate improved MOCART (magnetic resonance observation of cartilage repair tissue) scores and functional outcome scores at a minimum 2 years after surgery. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective analysis was performed comparing patients treated with AOT/CBMA alone and AOT with CBMA/EMCA. Clinical outcomes were evaluated with the Foot and Ankle Outcome Score. Magnetic resonance imaging appearance was evaluated with the use of the MOCART (magnetic resonance observation of cartilage repair tissue) score. Cyst formation was also evaluated on postoperative magnetic resonance imaging. Results: A total of 26 patients were included in the AOT + CBMA/EMCA group (10 male, 16 female), and 34 patients were included in the AOT/CBMA group (17 male, 17 female). The mean Foot and Ankle Outcome Score significantly improved in both groups ( P < .001) across all subscales (symptoms, pain, activities of daily living, sports activities, and quality of life), but there was no significant difference between groups at final follow-up. There was no significant difference in mean MOCART scores between the groups ( P = .118). In the AOT/CBMA group, 3 patients (8.8%) complained of knee pain, and 1 (2.9%) required additional surgery (hardware removal). In the AOT + CBMA/EMCA group, 2 patients (7.7%) complained of knee pain, and 6 patients (23%) required additional surgery (3 hardware removals and 3 arthroscopic debridements of scar tissue in the ankle). Conclusion: We found that while EMCA with CBMA has benefit in regeneration and repair of OLT treated with bone marrow stimulation, there appears to be little benefit of EMCA over CBMA alone as a physiologic grout at the graft-host interface in OLT treated with AOT.

Early investigations into the magnetic resonance imaging (MRI) appearance of articular cartilage imaging relied on assessment of the morphology, with subsequent investigators reporting identifying increased T2 signal intensity, bright signal, in degenerated cartilage. The cartilage “black line sign” is a finding that has recently been described in the radiology literature to characterize cartilage pathology. This sign refers to a focal linear hypointense signal within articular cartilage that is oriented perpendicular to the subchondral bone on T2-weighted MRI. The diagnostic significance and clinical relevance of this sign is debated. Since its first description, several papers have further delineated the etiology, prevalence, and clinical relevance of these and other dark cartilage abnormalities. The intent of this article is to summarize these findings, with hopes of bringing to light the importance of dark cartilage lesions and their clinical implication in the world of knee surgery. We will briefly discuss the most probable etiologies of dark cartilage abnormalities and the major factors determining the unique signal intensity. The described anatomical patterns of this finding, the clinical importance, potential mimics, and current treatment recommendations will be reviewed.

We investigated the analgesic effects of tramadol and the arthritic changes following tramadol administration in the rat hip osteoarthritis (OA) model using mono-iodoacetate (MIA). The right hip joints of male Sprague-Dawley rats (n = 5 rats/group) in the Sham group were injected with 25 μl of sterile saline and 1% of fluorogold (FG) retrograde neurotracer. In the MIA + Vehicle and MIA + Tramadol groups, FG and 25 μl of sterile saline with 0.5 mg of MIA were injected into the right hip joint. The MIA + Vehicle and MIA + Tramadol groups were administered daily for 4 weeks, either sterile saline (10 mg/kg, intraperitoneal [i.p.]) or tramadol (10 mg/kg, i.p.). We assessed hyperalgesia every week after MIA administration. Histopathological changes and immunoreactive neurons for calcitonin gene-related peptide (CGRP) in dorsal root ganglia (DRG) were evaluated after 4 weeks of treatment. MIA injection into the hip joint led to mechanical hyperalgesia (p < 0.01), which was significantly reduced by tramadol administration (p < 0.01). Furthermore, daily i.p injection of tramadol significantly suppressed CGRP expression in DRG (p < 0.0001). MIA + Vehicle and MIA + Tramadol groups showed significant cartilage reduction and degeneration compared to the Sham group (p < 0.0001). Interestingly, OA changes significantly progressed in the MIA + Tramadol group compared to the MIA + Vehicle group (p < 0.0001).

PURPOSE To assess the clinical outcome and survival of an inlay resurfacing prosthesis for focal femoral condyle chondral and osteochondral defects. METHODS Two hundred sixty-six patients (mean age, 38.25 years; range 25-56 years) with symptomatic femoral condyle chondral and osteochondral defects were reviewed. The mean follow-up period was 7.3 years (range 5-10 years). The medial femoral condyle was involved in 229 and the lateral condyle in 37 patients. Previous cartilage surgery was done in 235 patients. All patients were treated with focal femoral condyle resurfacing with the HemiCAP® device. The preoperative and the last follow-up values of the Knee Injury and Osteoarthritis Outcome Score (KOOS), Oxford Knee Score (OKS), 36-item Short Form Survey (SF-36) and Visual Analogue Scale (VAS) were examined. Complications, reoperation rate and survival were analyzed. RESULTS At the last follow-up, all clinical score values showed significant improvement as compared with the corresponding preoperative values (p

OBJECTIVE To investigate the mechanism of and potential contributing factors to temporomandibular joint osteoarthritis (TMJOA) caused by oestrogen deficiency with a persistent high bite force. MATERIALS AND METHODS A TMJOA model was generated by subjecting 6-week-old female rats to ovariectomy (OVX) and feeding them a hard feed. The rats (n = 12/group) were divided into sham (control); OVX; OVX+hard feed (HF); OVX+hard feed+local-joint injection of 17β-oestradiol (an oestrogen) (E2); and OVX+hard feed+local-joint injection of rapamycin (an autophagy activator) (RAPA)groups. Condyles were stained with haematoxylin-eosin and Safranin O Fast Green. The expression of Beclin 1, LC3 and p-mTOR in condylar cartilages was analysed. RESULTS Tissue staining revealed thinner condylar cartilage, varying numbers or fewer hypertrophic chondrocytes, and lower proteoglycan content in the cartilage matrix of the OVX group. These characteristics were more pronounced in the HF group, but were significantly recovered in the E2 and RAPA groups. Immunohistochemical staining revealed significantly lower autophagic flux in OVX/HF groups and a higher one in E2/RAPA groups. CONCLUSIONS A persistent high bite force could aggravate TMJOA induced by oestrogen deficiency, and the application of oestrogen or rapamycin could delay its progression. Additionally, autophagy may play a role in the development of TMJOA.

Objective To investigate the role of autologous platelet‐rich plasma (PRP) on the repair of meniscal white‐white zone injury through promoting the proliferation of canine bone marrow‐derived mesenchymal stem cells (BMSCs). Methods A total of 24 beagle dogs were selected to construct meniscal white‐white zone injury models in both lateral knee joints. All subjects were divided into four groups: control, BMSCs, PRP, and PRP + BMSCs. Immunohistochemistry was applied in the expression detection of type I and type II collagens. HE staining and methylene blue staining were performed to observe the injury of cartilage of lateral femoral condyle in each group. ELISA was used to detect the osteopontin (OPN) content in cartilage of lateral femoral condyle. HE staining and magnetic resonance imaging (MRI) were used to observe the healing of meniscus in each group. Outcome measures include the expression of OPN in the synovial fluid of knee joint, the expression of type I collagen and type II collagen, the healing of meniscus injury, and the damage degree of lateral femoral condyle cartilage. Results Compared with the control group, the expressions of type I and type II collagens were enhanced in the PRP group and the PRP + BMSCs group. Compared with 1 week before modeling, the expression of OPN was elevated in the control group and the BMSCs group at 3 weeks after modeling. There were no significant differences in the above indicators between the PRP group and the PRP + BMSCs group. According to MRI and pathological section after HE staining, meniscal healing in the PRP group and the PRP + BMSCs group was significantly improved as compared to that of the control group and the BMSCs group (all P 0.05). All subjects were divided into the non‐healing group and the healing group in accordance with the HE staining results in previous experiment. The injury of cartilage of lateral femoral condyle was significantly heavier in the non‐healing group than that in the healing group. Conclusion The application of PRP alone or in combination with BMSCs could promote the clinical healing rate of meniscal white‐white zone injury., The study investigates the role of autologous platelet‐rich plasma (PRP) on the repair of meniscal white‐white zone injury through promoting the proliferation of canine bone marrow‐derived mesenchymal stem cells (BMSCs).The application of PRP alone or in combination with BMSCs could promote the clinical healing rate of meniscal white‐white zone injury.

Introduction: The unique anatomy of the ear makes the reconstruction more challenging. Microtia and auricula hematomas are deformities or defects that can occur in the ear. Treating traumatic injury and congenital malformations of the ears needs some technique and expertise. Hyperbaric Oxygen Therapy is an additional therapy that makes a significant contribution and is effective in wound healing. Case Series: In our first case, a 52-year-old man presented with a traumatic right cauliflower ear due to a traffic accident two weeks before hospital admission. The second case involves a boy 14-year-old who has a Microtia in the right ear with total ear construction performed using autologous costochondral cartilage techniques in a two-stage. Results: Both cases following hyperbaric oxygen therapy, yield good results with good scars, no sign of infection nor tissue necrosis Summary: The combination therapy of reconstructive surgery and administration of oxygen therapy gave satisfactory results in both cases. Five sessions of hyperbaric treatment showed promising results. There is no infection, rapid wound healing, and cessation of flap compromise.

Актуальность. На сегодняшний день в лечении внутрисуставных переломов доминируют технологии открытой репозиции и погружного остеосинтеза. При наличии множества положительных качеств, характерных для этих технологий, объективным негативным фактором является их высокая травматичность, обусловливающая значительное количество ранних гнойно-некротических осложнений и поздних нарушений регенерации. Эти обстоятельства вынуждают вновь заострить внимание на объективизации показаний для открытых хирургических вмешательств при тяжелых внутрисуставных травматических повреждениях. Закрытые технологии лечения внутрисуставных переломов не вызывают вопросов в отношении травматичности и риска гнойно-некротических осложнений, но репозиционные возможности внеочагового остеосинтеза и фиксационного метода считаются ограниченными. Один из путей улучшения функциональных результатов закрытых технологий — использование эффекта функционального ремоделирования. Это явление замечено в клинической практике, когда первичные сомнительные результаты закрытой репозиции отломков существенно улучшались в процессе функционального лечения, и последующие функциональные результаты лечения оказывались вполне приемлемыми. Такие положительные перспективы потребовали углубленного изу-чения и определения условий, необходимых для реализации эффекта функционального ремоделирования, и в первую очередь — оптимальных сроков для начала функционального лечения. Вопрос о сроках возник не случайно, так как существующий тезис «чем раньше, тем лучше» на практике выглядит сомнительно и, кроме того, не имеет никакой доказательной базы. Цель. На основании изучения структурных изменений в полнослойном дефекте суставной поверхности установить оптимальные временные параметры проведения реабилитационного лечения для реализации эффекта функционального ремоделирования. Материалы и методы. Выполнено экспериментальное исследование на 28 половозрелых крысах, которым после артротомии коленного сустава наносили стандартные травматические повреждения наружного мыщелка бедренной кости. Для стандартизации механизма травмы разработано специальное устройство. Подопытных животных объединили в 4 группы по 7 особей, которых выводили из эксперимента в сроки 3, 7, 14, 28 дней после травмы, и выполняли гистоморфологическое исследование препаратов из зоны повреждения. Результаты. Установлено, что на протяжении первых двух недель после травмы в зоне повреждения проходят регенеративные процессы с образованием органоспецифичных структур, однако механические свойства регенерата еще не достаточны для первичного обездвиживания краев хрящевого дефекта, что, как доказано, является основным условием для образования хрящеподобной ткани. По этой причине функциональное лечение в этот период может только замедлить процесс регенерации. На 14-е сутки констатировано интенсивное формирование костной ткани субхондральных зон, что является прогностически позитивным признаком, от которого (что также доказано) прямо зависит регенерация хряща. Этим манифестируются признаки готовности регенерата к ремоделированию хрящевых дефектов. На протяжении последних двух недель наблюдалось моделирование суставных поверхностей путем заместительного заполнения дефектов костной тканью пластинчатой структуры и формирование волокнистого хряща; восстановления гиалинового хряща не происходило. Выводы. Обоснованными сроками начала функционального лечения является период с начала третьей и не позднее конца четвертой недели после травмы, что является оптимальным для реализации эффекта функционального ремоделирования поврежденных суставных поверхностей.

The aims of the present study were: (1) to characterize the bone-marrow aspirate (BMA) obtained with a centrifuge-free process, employing a dedicated aspiration device; (2) to test the in vitro efficacy of BMA in a model of cartilage inflammation; and (3) to report the preliminary clinical results in a small cohort of patients affected by knee OA. Ten patients (4 M, 6 W; mean age: 51.9 ± 9.2 yy) affected by mild to moderate unicompartmental knee OA (KL grade 2–3) were treated by intra-articular and subchondral injections of BMA obtained by a centrifuge-free process. To evaluate the effectiveness of the device in harvesting mesenchymal stem cells (MSCs), samples of the obtained BMA were tested by flow cytometry before and after subculture; BMA ability to counteract inflammation was also tested in an in vitro model of cartilage cell inflammation, evaluating the expression of MMP1, MMP3, TGFβ and TIMP-1 by real-time PCR. Patients were also evaluated up to two years’ follow-up by using: VAS for pain, IKDC-subjective and KOOS scores. The laboratory analysis showed that BMSCs accounted for 0.011% of BMA cells, similar to what had been expected in native bone marrow. The paracrine activity of BMA was able to reduce in vitro the catabolic response of human chondrocyte, as shown by the decrease in metalloproteases concentration and increase in anti-inflammatory mediators. Moreover, the clinical evaluation showed significant improvements in all scores adopted, with stable results up to two years. The present data showed the effectiveness of the study device to harvest pure bone marrow with minimal peripheral blood contamination. The relevant content of MSCs resulted in the ability to counteract the catabolic cascade through a paracrine action. The clinical outcomes in patients affected by unicompartmental knee OA were encouraging in terms of pain reduction and functional improvement up to mid-term evaluation.

Localized cartilage lesions in early osteoarthritis and acute joint injuries are usually treated surgically to restore function and relieve pain. However, a persistent clinical challenge remains in how to repair the cartilage lesions. We expressed doublecortin (DCX) in human adipose-derived stromal/stem cells (hASCs) and engineered hASCs into cartilage tissues using an in vitro 96-well pellet culture system. The cartilage tissue constructs with and without DCX expression were implanted in the knee cartilage defects of rabbits (n = 42) and monkeys (n = 12). Cohorts of animals were euthanized at 6, 12, and 24 months after surgery to evaluate the cartilage repair outcomes. We found that DCX expression in hASCs increased expression of growth differentiation factor 5 (GDF5) and matrilin 2 in the engineered cartilage tissues. The cartilage tissues with DCX expression significantly enhanced cartilage repair as assessed macroscopically and histologically at 6, 12, and 24 months after implantation in the rabbits and 24 months after implantation in the monkeys, compared to the cartilage tissues without DCX expression. These findings suggest that hASCs expressing DCX may be engineered into cartilage tissues that can be used to treat localized cartilage lesions.

Introduction: In recent years, genetic engineering has made outstanding contributions to sports, and it has played a huge role in promoting the development of sports-related fields. Objective: We analyze the tissue source of bone growth and healing by studying the role of bone morphogenetic protein and transforming growth factors in fracture injuries caused by sports. Methods: We established a human fracture model to express the shape and content of bone morphogenetic protein and transforming growth factor during fracture healing. Results: In the fracture healing stage caused by different sports, the expression levels of the two genes are different. Bone morphogenetic protein has a high content in the osteogenesis stage of the membrane, while transforming growth factor is high in the cartilage ossification stage. Conclusion: Gene therapy for fractures caused by physical exercise has certain advantages. Osteoblasts and chondrocytes are involved in the synthesis of transforming growth factors. Level of evidence II; Therapeutic studies - investigation of treatment results. RESUMO Introdução: Nos últimos anos, a engenharia genética tem contribuído de forma notável para os esportes, além de ter uma função importante na promoção do desenvolvimento de áreas relacionadas ao esporte. Objetivo: Analisamos a origem de tecidos do crescimento ósseo e sua regeneração através do estudo da proteína morfogenética óssea e fatores de transformação do crescimento em fraturas causadas pela prática do esporte. Métodos: Criamos um modelo de fratura humana para expressar a forma e o conteúdo da proteína morfogenética óssea e de fatores de transformação do crescimento durante a recuperação de fraturas. Resultados: Na fase de recuperação da fratura causada por diversos esportes, os níveis de expressão dos dois genes são diferentes. A proteína morfogenética óssea se apresenta em alta quantidade na fase osteogenetica da membrana, e o fator de transformação de crescimento apresenta alta quantidade na fase de ossificação da cartilagem. Conclusão: A terapia genética para fraturas causadas por exercícios físicos apresenta diversas vantagens. Osteoblastos e condrócitos tem um papel na síntese dos fatores de transformação do crescimento. Nível de evidência II; Estudos terapêuticos – investigação de resultados de tratamento. RESUMEN Introducción: En los últimos años, la ingeniería genética ha contribuido de forma notable para los deportes, además de tener una función importante en la promoción del desarrollo de áreas relacionadas al deporte. Objetivo: Analizamos el origen de tejidos del crecimiento óseo y su regeneración a través del estudio de la proteína morfogenética ósea y factores de crecimiento transformante en fracturas causadas por la práctica del deporte. Métodos: Creamos un modelo de fractura humana para expresar la forma y el contenido de la proteína morfogenética ósea y de factores de crecimiento transformante durante la recuperación de fracturas. Resultados: En la fase de recuperación de la fractura causada por diversos deportes, los niveles de expresión de los dos genes son diferentes. La proteína morfogenética ósea se presenta en alta cantidad en la fase osteogénica de la membrana, y el factor de crecimiento transformante presenta alta cantidad en la fase de osificación del cartílago. Conclusión: La terapia genética para fracturas causadas por ejercicios físicos presenta diversas ventajas. Osteoblastos y condrocitos tienen un papel en la síntesis de los factores de crecimiento transformante. Nivel de evidencia II; Estudios terapéuticos – investigación de resultados de tratamiento.

Objective Treatment of circumscribed cartilage defects in the first metatarsophalangeal joint (MTP1) using autologous cartilage fragments. Indications Full thickness cartilage defects (ICRS IV) or focal osteoarthritis in combination with hallux rigidus. Contraindications Pre-existing ankylosis of the metatarsophalangeal joint; global osteoarthritis of the joint; advanced osteoarthritis of the sesamoidal articulation; osteonecrotic cysts in the head of the first metatarsal bone. Surgical technique Preparation of the metatarsophalangeal joint. Mobilization of the first metatarsal head. Harvesting of the cartilage fragments from the dorsal rim portion as part of the cheilectomy. Mincing the cartilage fragments with a 3.0 mm shaver in sterile conditions. Augmenting the cartilage fragments with autologous conditioned plasma (ACP). Preparing the defect area and creation of a "contained" defect. Replantation of the resulting minced cartilage mass into the defect of the articular surface on the first metatarsal head. Postoperative management Immobilization of the MTP1 for 48 h. Intensive physiotherapy for 3 months. Full weight bearing after reduced swelling. Results In 2020, 5 patients were treated with the method described and followed up for a period of 1 year. All patients were subjectively satisfied with the result of the operation. There were no relevant surgery-associated complications.

Background Reconstruction of congenital microtia remains challenging, particularly in patients with a history of ear canaloplasty due to insufficient regional soft tissue. The insertion of a tissue expander prior to implantation of the cartilage framework has traditionally been employed. However, this procedure could induce additional morbidity. Herein, we present a method using V-Y advancement of a temporal triangular flap to gain additional soft tissue in these challenging cases. Methods Congenital microtia patients with a history of ear canaloplasty who underwent auricular reconstruction using the Nagata technique between 2016 and 2020 were reviewed. To obtain additional soft tissue, V-Y advancement of a temporal triangular flap was performed concurrently with implantation of the costal cartilage framework, without prior insertion of a tissue expander. The outcomes of these patients with respect to postoperative complications and esthetics were evaluated. Results Eight patients with bilateral lesions were included. No specific complications developed after the first-stage surgery. However, one patient experienced complications after the second stage (auricular elevation). An analysis of the esthetic results showed most patients had excellent outcomes, achieving a satisfactory convolution. The median number of operations needed to complete reconstruction was 2, which was fewer than required using the conventional method with prior insertion of a tissue expander. Conclusions In patients with a history of previous canaloplasty, V-Y advancement of a temporal triangular flap could serve as an alternative to tissue expansion for microtia reconstruction. This technique provided reliable and satisfactory results with a reduced number of surgical stages.