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Aims and Objectives: To evaluate the measured fall risk score that more accurately reflects the changeable conditions in acute care settings, and to efficiently evaluate the association between falls and fall risk score., Background: The Morse Fall Scale (MFS) is a well-known easy-to-use tool, while the Johns Hopkins Fall Risk Assessment Tool (JHFRAT) consists of items with high specificity. Evaluating suitable fall-risk assessment tools to measure these changeable conditions may contribute to preventing falls in acute care settings., Design: Retrospective case-control study using the STROBE checklist., Methods: In an acute care setting (708-bedded university hospital with a regional emergency medical centre), the non-fall group was adjusted to fall group using propensity score matching. According to the fall rate of 3-5%, non-fall groups for each tool were selected (1386 and 1947) from the before adjusted data, and the fall groups included 42 and 59. The applied covariates were individual characteristics that ordinarily changed such as age, gender, diagnostic department and hospitalisation period. The adjusted data were analysed using generalised estimating equations and mixed effect model., Results: After adjustment, the fall group measured using the JHFRAT had a significantly higher difference between the initial and re-measured total score than the non-fall group. The JHFRAT, especially with the re-measured score, had a higher AUC value for predicting falls than the MFS. MFS's sensitivity was 85.7%, and specificity was 58.8% at 50 points; for JHFRAT, these were 67.8% and 80.2% at 14 points, respectively. These cut-off points were used to evaluate validity during tool development and are commonly used as reference scores., Conclusions: JHFRAT more accurately reflects acute changeable conditions related to fall risk measurements after admission., Relevance to Clinical Practice: JHFRAT may be useful for effective fall prevention activities in acute care settings., (© 2021 John Wiley & Sons Ltd.)

Osteoarthritis (OA) reduces the quality of life as a result of the pain caused by continuous joint destruction. Inactivated Lactobacillus (LA-1) ameliorated osteoarthritis and protected cartilage by modulating inflammation. In this study, we evaluated the mechanism by which live LA-1 ameliorated OA. To investigate the effect of live LA-1 on OA progression, we administered LA-1 into monosodium iodoacetate (MIA)-induced OA animals. The pain threshold, cartilage damage, and inflammation of the joint synovial membrane were improved by live LA-1. Furthermore, the analysis of intestinal tissues and feces in the disease model has been shown to affect the systems of the intestinal system and improve the microbiome environment. Interestingly, inflammation of the intestinal tissue was reduced, and the intestinal microbiome was altered by live LA-1. Live LA-1 administration led to an increase in the level of Faecalibacterium which is a short-chain fatty acid (SCFA) butyrate-producing bacteria. The daily supply of butyrate, a bacterial SCFA, showed a tendency to decrease necroptosis, a type of abnormal cell death, by inducing autophagy and reversing impaired autophagy by the inflammatory environment. These results suggest that OA is modulated by changes in the gut microbiome, suggesting that activation of autophagy can reduce aberrant cell death. In summary, live LA-1 or butyrate ameliorates OA progression by modulating the gut environment and autophagic flux. Our findings suggest the regulation of the gut microenvironment as a therapeutic target for OA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cho, Na, Jhun, Woo, Lee, Lee, Lee, Um, Kim, Park and Cho.)

Background: Osteoarthritis (OA) is the most common type of degenerative arthritis and affects the entire joint, causing pain, joint inflammation, and cartilage damage. Various risk factors are implicated in causing OA, and in recent years, a lot of research and interest have been directed toward chronic low-grade inflammation in OA. Monocyte chemoattractant protein-1 (MCP-1; also called CCL2) acts through C-C chemokine receptor type 2 (CCR2) in monocytes and is a chemotactic factor of monocytes that plays an important role in the initiation of inflammation. The targeting of CCL2-CCR2 is being studied as part of various topics including the treatment of OA., Methods: In this study, we evaluated the potential therapeutic effects the sCCR2 E3 gene may exert on OA. The effects of sCCR2 E3 were investigated in animal experiments consisting of intra-articular injection of sCCR2 E3 in a monosodium iodoacetate (MIA)-induced OA rat model. The effects after intra-articular injection of sCCR2 E3 (fusion protein encoding 20 amino acids of the E3 domain of the CCL2 receptor) in a monosodium iodoacetate-induced OA rat model were compared to those in rats treated with empty vector (mock treatment) and full-length sCCR2., Results: Pain improved with expression of the sCCR2 gene. Improved bone resorption upon sCCR2 E3 gene activation was confirmed via bone analyses using micro-computed tomography. Histologic analyses showed that the sCCR2 E3 gene exerted protective effects against cartilage damage and anti-inflammatory effects on joints and the intestine., Conclusions: These results show that sCCR2 E3 therapy is effective in reducing pain severity, inhibiting cartilage destruction, and suppressing intestinal damage and inflammation. Thus, sCCR2 E3 may be a potential therapy for OA., (© 2022. The Author(s).)

Background: Tibial plateau fractures (TPFs) are a challenging type of fracture in orthopedic traumatology. We previously designed a plate (Patent Number: CN201520195596.5) for posterolateral TPF combined with posterior lateral collapse.. In this study, finite element analysis was used to compare the biomechanical characteristics of two internal fixation methods for posterolateral TPF. We investigated the support effect of the new steel plate on lateral TPFs combined with posterior TPFs., Methods: Two models of complex TPF were established. Model A was fixed with the new type of plate, and model B was fixed without the plate. Three axial loads of 500, 1,000, and 1,500 N were applied using FEA on the two fracture models (A and B) to analyze the data., Results: In model A, the maximum displacement at 500, 1,000, and 1,500 N was 0.085797, 0.17043, and 0.25465 mm, respectively; the maximum stress of the bone block was 11.285, 20.648, and 29.227 MPa, respectively; and the maximum strain of the bone block was 0.0012474, 0.007435, and 0.0035769 mm, respectively. The maximum displacement of the internal fixation was 0.096932, 0.18682, and 0.27655 mm, respectively; the maximum stress was 69.54, 112.1, and 155.71 MPa, respectively; and the maximum strain was 0.00066228, 0.0010676, and 0.0014829 mm, respectively. In model B, the maximum displacement of fractures at 500, 1,000, and 1,500 N was 0.15675, 0.29868, and 0.44017 mm, respectively; the maximum stress of the bone block was 6.5519, 12.575, and 18.842 MPa, respectively; and the maximum strain of the bone block was 0.0032554, 0.0074357, and 0.012146 mm, respectively. The maximum displacement of the screw was 0.14177, 0.27109, and 0.39849 mm, respectively; the maximum stress was 48.916, 92.251, and 135.27 MPa, respectively; and the maximum strain was 0.00046608, 0.00087893, and 0.0012887 mm, respectively., Conclusions: The fixation method using this type of plates and screws can replace other methods using two plates to fix complex TPF., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-4529/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Osteoarthritis (OA) is the most common form of arthritis associated with ageing. Vitamin D has diverse biological effect on bone and cartilage, and observational studies have suggested it potential benefit in OA progression and inflammation process. However, the effect of vitamin D on OA is still contradictory. Here, we investigated the therapeutic potential of vitamin D in OA. Six-week-old male Wistar rats were injected with monosodium iodoacetate (MIA) to induce OA. Pain severity, cartilage destruction, and inflammation were measured in MIA-induced OA rats. Autophagy activity and mitochondrial function were also measured. Vitamin-D (1,25(OH) 2 D3) and celecoxib were used to treat MIA-induced OA rats and OA chondrocytes. Oral supplementation of vitamin D resulted in significant attenuations in OA pain, inflammation, and cartilage destruction. Interestingly, the expressions of MMP-13, IL-1β, and MCP-1 in synovial tissues were remarkably attenuated by vitamin D treatment, suggesting its potential to attenuate synovitis in OA. Vitamin D treatment in OA chondrocytes resulted in autophagy induction in human OA chondrocytes and increased expression of TFEB, but not LC3B, caspase-1 and -3, in inflamed synovium. Vitamin D and celecoxib showed a synergistic effect on antinociceptive and chondroprotective properties in vivo . Vitamin D showed the chondroprotective and antinociceptive property in OA rats. Autophagy induction by vitamin D treatment may be a promising treatment strategy in OA patients especially presenting vitamin D deficiency. Autophagy promoting strategy may attenuate OA progression through protecting cells from damage and inflammatory cell death., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interest., (Copyright © 2022. The Korean Association of Immunologists.)

Articular cartilage has unique biological and biomechanical characteristics. Damage to this tissue fails to heal spontaneously, leading to progressive arthritis. Cartilage repair techniques have been looked forward to in the treatment of significant cartilage injuries. Cell-based regenerative techniques like the two-staged cultured chondrocytes and single-stage mesenchymal cell transplantation have been tried with varying results and limitations. We study the outcomes of cultured bone marrow derived MSCs in the treatment of articular cartilage defects of the knee in comparison to autologous cultured chondrocyte implantation (ACI). Both cultured MSC and ACI treatment methods resulted in significant improvements in patient reported outcome measures (PROMs). There was no difference in the PROMs, MOCART scores, T2∗ mapping and dGEMRIC values between the groups. Use of cultured MSCs leads to good clinical outcomes similar to ACI and represents a promising treatment to restore the articular cartilage in the knee., (© 2022 Delhi Orthopedic Association. All rights reserved.)

Previously, most fractures have been treated through bone reduction and immobilization. With an increase in the patients' need for an early return to their normal function, development in surgical techniques and materials have accelerated. However, delayed union or non-union of the fracture site sometimes inhibits immediate return to normal life. To enhance fracture healing, diverse materials and methods have been developed. This is a review on the current modalities of fracture healing enhancement, which aims to provide a comprehensive knowledge regarding fracture healing for researchers and health practitioners., (© 2021. The Korean Tissue Engineering and Regenerative Medicine Society.)

Background: Osteoarthritis, one of the most common joint diseases, is characterized by the loss of joint function due to articular cartilage destruction. Herein, we review current and previous research involving the clinical applications of arthritis therapy and suggest potential therapeutic options for osteoarthritis in the future., Past, Present, and Future Treatment: The arthroscopic cartilage regeneration procedure or realignment osteotomy has been performed as a joint-conserving procedure in cases where conservative treatment for damaged articular cartilage and early osteoarthritis failed. If cartilage regeneration is ineffective or if the joint damage progresses, arthroplasty is the main treatment option. The need for biological arthritis treatment has expanded as the healthy lifespan of the global population has increased. Accordingly, minimally invasive surgical treatment has been developed for the treatment of damaged cartilage and early osteoarthritis. However, patients generally prefer to avoid all types of surgery, including minimally invasive surgery. Therefore, in the future, the treatment of osteoarthritis will likely involve injection or medication., Conclusion: Currently, arthritis management primarily involves the surgical application of therapeutic agents to the joints. However, nonsurgical or prophylactic methods are expected to become mainstream arthritis therapies in the future., (© 2022. The Author(s).)

Chondrocytes secrete massive extracellular matrix (ECM) molecules that are produced, folded, and modified in the endoplasmic reticulum (ER). Thus, the ER-associated degradation (ERAD) complex-which removes misfolded and unfolded proteins to maintain proteostasis in the ER- plays an indispensable role in building and maintaining cartilage. Here, we examined the necessity of the ERAD complex in chondrocytes for cartilage formation and maintenance. We show that ERAD gene expression is exponentially increased during chondrogenesis, and disruption of ERAD function causes severe chondrodysplasia in developing embryos and loss of adult articular cartilage. ERAD complex malfunction also causes abnormal accumulation of cartilage ECM molecules and subsequent chondrodysplasia. ERAD gene expression is decreased in damaged cartilage from patients with osteoarthritis (OA), and disruption of ERAD function in articular cartilage leads to cartilage destruction in a mouse OA model.

Osteoarthritis (OA) is a common degenerative joint disease characterized by breakdown of joint cartilage. Mitochondrial dysfunction of the chondrocyte is a risk factor for OA progression. We examined the therapeutic potential of mitochondrial transplantation for OA. Mitochondria were injected into the knee joint of monosodium iodoacetate-induced OA rats. Chondrocytes from OA rats or patients with OA were cultured to examine mitochondrial function in cellular pathophysiology. Pain, cartilage destruction, and bone loss were improved in mitochondrial transplanted-OA rats. The transcript levels of IL-1β, TNF-α, matrix metallopeptidase 13, and MCP-1 in cartilage were markedly decreased by mitochondrial transplantation. Mitochondrial function, as indicated by membrane potential and oxygen consumption rate, in chondrocytes from OA rats was improved by mitochondrial transplantation. Likewise, the mitochondrial function of chondrocytes from OA patients was improved by coculture with mitochondria. Furthermore, inflammatory cell death was significantly decreased by coculture with mitochondria. Mitochondrial transplantation ameliorated OA progression, which is caused by mitochondrial dysfunction. These results suggest the therapeutic potential of mitochondrial transplantation for OA., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interest., (Copyright © 2022. The Korean Association of Immunologists.)

The green-lipped mussel (GLM) contains novel omega-3 polyunsaturated fatty acids, which exhibit anti-inflammatory and joint-protecting properties. Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive loss of cartilage; oxidative stress plays a role in the pathogenesis of OA. The objectives of this study were to investigate the in vivo effects of the GLM on pain severity and cartilage degeneration using an experimental rat OA model, and to explore the mode of action of GLM. OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) into the knee. Oral GLM was initiated on the day after 3dyas of MIA injection. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. Samples were analyzed both macroscopically and histologically. Immunohistochemistry was used to investigate the expression of interleukin-1β (IL-1β), IL-6, nitrotyrosine, and inducible nitric oxide synthase (iNOS) in knee joints. Also, the GLM was applied to OA chondrocyte, and the expression on catabolic marker and necroptosis factor were evaluated by real-time polymerase chain reaction. Administration of the GLM improved pain levels by preventing cartilage damage and inflammation. GLM significantly attenuated the expression levels of mRNAs encoding matrix metalloproteinase-3 (MMP-3), MMP-13, and ADAMTS5 in IL-1β-stimulated human OA chondrocytes. GLM decreased the expression levels of the necroptosis mediators RIPK1, RIPK3, and the mixed lineage kinase domain-like protein (MLKL) in IL-1β-stimulated human OA chondrocytes. Thus, GLM reduced pain and cartilage degeneration in rats with experimentally induced OA. The chondroprotective properties of GLM included suppression of oxidative damage and inhibition of catabolic factors implicated in the pathogenesis of OA cartilage damage. We suggest that GLM may usefully treat human OA., Competing Interests: The authors have declared that no competing interests exist.

Osteonecrosis of femoral head (ONFH) is a disease of the femoral head and can cause femoral head collapse and arthritis. This can lead to pain and gait disorders. ONFH has various risk factors, it is often progressive, and if untreated results in secondary osteo-arthritis. Biological therapy makes use of bone marrow concentrate, cultured osteoblast and mesenchymal stem cell (MSC) obtained from various sources. These are often used in conjunction with core decompression surgery. In this review article, we discuss the current status of cell therapy and its limitations. We also present the future development of biological approach to treat ONFH., (© 2021.)

Articular cartilage injuries are common. The diagnosis of these injuries is often delayed and may lead to early osteoarthritis. Treatment depends on many factors but mainly on the stage and size of the lesion. The anatomy of articular cartilage is complex, and it is an avascular, aneural, and alymphatic structure. Recently, more emphasis is laid on its anatomy and biomechanics to understand the regeneration process of articular cartilage., (© 2021 Delhi Orthopedic Association. All rights reserved.)

The articular cartilage of the joint is the thin viscoelastic layer of the connective tissue. It has a unique anatomy and physiology, which makes the repair of the articular cartilage damage more difficult and challenging due to its limited healing capacity. Increasing knowledge regarding the importance of articular cartilage for joint preservation has led to increased attention on early identification of cartilage damage as well as degeneration in order to delay osteoarthritis. There are various treatment modalities ranging from preventive management, physical therapy, pharmacological, non-pharmacological and surgical treatments exist in current literature. However most of the studies have limited long term follow up and mainly consists of small case series and case reports. This is an up to date concise review discussing the available management options for articular cartilage damage starting to lifestyle modification to pharmacotherapy, physiotherapy, and osteobiologics till various joint preservation techniques that have been in use currently., (© 2021 Delhi Orthopedic Association. All rights reserved.)

Background: A midshaft clavicle fracture is a common fracture that typically responds well to open reduction and internal fixation (ORIF). However, refracture can occur after implant removal (IR). This study aimed to analyze the rate of refracture and related factors after removal of the locking compression plate (LCP) for displaced midshaft clavicle fractures., Methods: We retrospectively reviewed the medical records of 201 patients who had undergone ORIF with LCP for midshaft clavicle fractures after IR after bony union from January 2011 to May 2018 at our institute. We evaluated basic demographic characteristics and radiographic parameters. All patients were treated with an LCP for primary fracture. The patients were divided into two groups: a refracture group that experienced a second fracture within 1 year after IR and a no-fracture group., Results: There were four cases (1.99%) of refracture; three were treated conservatively, while one was treated surgically. All patients achieved bony union. The average interval between refracture and IR was 64 days (range, 6-210 days). There was a significant difference in classification of fractures (AO Foundation/Orthopaedic Trauma Association [AO/OTA] classification) between the two groups. However, other patient demographics and radiographic measurements between refracture and IR, such as bone diameter, showed no significant difference between the two groups., Conclusions: This study showed that one in 50 patients suffered from refracture after removal of the LCP. Thus, if patients desire IR, the surgeon should explain that there is a relatively higher possibility of refracture for cases with simple or segmental fractures than for other types of fracture.

Background: Locked posterior fracture-dislocation of the shoulder (LPFDS) is a very rare injury that occurs predominantly in young patients following high-energy trauma. The long-term outcome of the treatment of this injury is often poor. This study sought to present the characteristics of injury, discuss the pathological anatomy, and to report the treatment outcomes of our case series., Methods: Between January 2012 and May 2018, a total of 234 patients who underwent surgical treatment for proximal humerus fractures were reviewed. Among them, six patients (mean age, 54.7 years; range, 35-76 years) with LPFDS were included in this study. Four patients were treated with open reduction and internal fixation (ORIF) with locking plates, one with hemiarthroplasty, and one with reverse total shoulder arthroplasty. Clinical results were evaluated by Constant, American Shoulder and Elbow Surgeons (ASES), and visual analog scale (VAS) scores and radiologic evaluation was conducted using follow-up radiographs., Results: The mean length of follow-up was 26.2 months (range, 12-54). The mean Constant, ASES, and VAS scores were 66.7, 65.5, and 2.2, respectively. Four patients who underwent ORIF achieved bony union, but avascular necrosis (AVN) of the humeral head was observed in two patients. No complications were observed in the patients who underwent arthroplasty surgery until final follow-up., Conclusions: In the treatment of LPFDS, replacement arthroplasty can produce predictable results. The approach of ORIF may be considered as a first choice of treatment in young patients but is sometimes correlated with postoperative complications such as AVN and the functional outcomes may be unpredictable. Therefore, patients should undergo careful diagnosis and treatment of this type of injury., Competing Interests: Conflict of interest None., (Copyright © 2020 Korean Shoulder and Elbow Society.)

Disease-modifying osteoarthritis (OA) therapy is not yet available. Several adjuvant therapies have demonstrated promising results in the treatment of OA. The present study aimed to investigate the therapeutic effects and underlying mechanisms of a combination of Lactobacillus acidophilus, vitamin B, and curcumin in the treatment of OA. Monosodium iodoacetate (MIA)-induced arthritis of the knee joint in rat was used as an animal model of human OA. The combination of L. acidophilus LA-1, vitamin B, and curcumin or a saline solution was given orally. Pain was measured according to the paw withdrawal latency, and paw withdrawal threshold. Cartilage destruction was analyzed using histomorphological techniques and the Mankin scoring system. Protein expression in the joint was examined using immunohistochemistry. The effects of the combination of L. acidophilus LA-1, vitamin B, and curcumin on mRNA levels in chondrocytes stimulated with interleukin (IL)-1β were analyzed using real-time polymerase chain reaction. The combination of L. acidophilus, vitamin B, and curcumin effectively downregulated Th17 cells and the related cytokine IL-17, thereby maintained the Treg population, and increased the expression of the Treg-related cytokine IL-10 in human peripheral blood mononuclear cells. The OA animal model exhibited reduced pain and preservation of cartilage in response to the combination treatment. The expression levels of pro-inflammatory cytokines and the catabolic, matrix metalloproteinase-13 (MMP-13), were decreased, whereas the expression of the anabolic tissue inhibitors of metalloproteinases (TIMPs) were upregulated in response to the drug combination. The combination of L. acidophilus, vitamin B, and curcumin was beneficial in OA treatment, controlling the inflammatory response via regulation of the Th17/Treg population and reducing the expression of pro-inflammatory cytokines in human peripheral blood mononuclear cells. The combination treatment also preserved cartilage, suppressed osteoclastogenesis, and regulated the anabolic/catabolic imbalance. These findings indicate the therapeutic potential of combination use of L. acidophilus, vitamin B, and curcumin in patients with OA., (Copyright © 2020. Published by Elsevier B.V.)

Purpose: The autologous collagen-induced chondrogenesis technique is described, and the results of a 6-year follow-up clinical study using this technique are presented., Methods: 30 patients with International Cartilage Repair Society (ICRS) Grade III/IVa symptomatic chondral defects of the knee treated with enhanced microdrilling using atelocollagen were prospectively examined in this clinical series. The median age of the patients was 39.0 years (range 19-61 years). Patients were followed up to 72 months. Clinical evaluation was performed using functional knee scores and radiologically. Both quantitative and qualitative assessments were performed., Results: Statistically significant and clinically relevant improvement was observed in 2 years and was sustained for the 6 years of the study observation. At 6 years, the mean Lysholm score was 79.7 (SD 6.8) compared to 52.6 (SD 10.7) pre-operatively (p < 0.05). The symptomatic Knee Injury and Osteoarthritis Outcome Score (KOOS) improved from 68.3 (SD 11.4) to 90.2 (SD 4.3) (p < 0.05). The subjective International Knee Documentation Committee (IKDC) also showed improvement from 39.1 (SD 4.1) to 81.6 (SD 7.8) (p  < 0.05). The calculated T2* relaxation times were 26.0 (SD 4.2) seconds and 30.3 (SD 6.2) seconds for the repair tissue and native cartilage, respectively. The average magnetic resonance observation of cartilage repair tissue (MOCART) score was 78.5 (SD 9.6) for all lesions., Conclusion: The enhanced microdrilling using atelocollagen is an enhancement of the traditional microfracture method using an off-the-shelf product. When used to treat moderate to severe chondral lesions, this enhancement produces hyaline-like cartilage with a corresponding improvement in symptoms., Level of Evidence: IV.

Background: The increasing prevalence of osteoarthritis among the old population worldwide is a great concern. Two of the biggest complaints of OA patients are joint pain and inflammation. Currently, people are relying on non-steroidal anti-inflammatory drugs (NSAIDs) and steroids to control pain and inflammation. However, long-term use of these pharmaceutical drugs has negative health consequences in the elderly, including gastro-intestinal, respiratory, and renal diseases. Natural products are receiving more attention than ever as alternative treatments against OA for their efficacies and safety. The root of Paeonia lactiflora Pal and the gum resin of Commiphora myrrha have been used as analgesics and anti-inflammatory agents since ancient time. A new herbal formula composed of P. lactiflora root and C. myrrha gum resin extracts, known as HT083, has shown promising antinociceptive and anti-inflammatory effects in a rodent model of OA. We design this study to investigate the safety and the efficacy of HT083 to prevent OA in patients with mild OA., Methods: This is a randomized, double-blind, and placebo-controlled study. A total of 100 eligible participants will be divided into two groups and will be given HT083 and a placebo for 12 weeks in 1:1 ratio. Treatment results will be assessed using a visual analog scale (VAS), Korean-Short Form health survey-36 score (SF-36), personal evaluation, and laboratory analysis., Discussion: This trial is expected to provide clinical evidence on the effectiveness and the safety of HT083 as a natural treatment for mild OA., Trial Registration: Korean Clinical Research Information Service (CRIS) number KCT0004925 Registered on 2020.04.16.

Effective engineering approaches for cartilage regeneration involve a combination of cells and biomaterial scaffolds. Multipotent mesenchymal stem cells (MSCs) are important sources for cartilage regeneration. Atelocollagen provides a suitable substrate for MSC attachment and enhancing chondrogenic differentiation. Here, we assessed the chondrogenic potential of adipose tissue derived human MSCs (hMSCs) mixed with atelocollagen gel. We observed cell attachment, viability, and microstructures by electron microscopy over 21 days. The levels of Sox9, type II collagen, aggrecan, type I collagen, Runx2, type X collagen, ALP, Osterix, and MMP13 were measured by RT-qPCR. Cartilage matrix-related proteins were assessed by enzyme-linked immunosorbent assay (ELISA), histology, and immunohistochemistry. hMSCs of all groups exhibited well-maintained cell survival, distribution and morphology. Abundant type II collagen fibers developed on day 21; while Sox9, type II collagen, and aggrecan expression increased over time in the atelocollagen group. However, type I collagen, RUNX2, type X collagen (CoL10A1), Osterix, and ALP were not expressed. These results corroborated the protein expression detected by ELISA. Further, histological analysis revealed lacunae-like structures, while staining demonstrated glycosaminoglycan accumulation. Cumulatively, these results indicate that atelocollagen scaffolds improve hMSC chondrogenic differentiation and are a potential approach for cartilage regeneration.

Background: High tibial osteotomy (HTO) is a well-established method for the treatment of medial compartment osteoarthritis of the knee with varus deformity. However, HTO alone cannot adequately repair the arthritic joint, necessitating cartilage regeneration therapy. Cartilage regeneration procedures with concomitant HTO are used to improve the clinical outcome in patients with varus deformity., Aim: To evaluate cartilage regeneration after implantation of allogenic human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) with concomitant HTO., Methods: Data for patients who underwent implantation of hUCB-MSCs with concomitant HTO were evaluated. The patients included in this study were over 40 years old, had a varus deformity of more than 5°, and a full-thickness International Cartilage Repair Society (ICRS) grade IV articular cartilage lesion of more than 4 cm 2 in the medial compartment of the knee. All patients underwent second-look arthroscopy during hardware removal. Cartilage regeneration was evaluated macroscopically using the ICRS grading system in second-look arthroscopy. We also assessed the effects of patient characteristics, such as trochlear lesions, age, and lesion size, using patient medical records., Results: A total of 125 patients were included in the study, with an average age of 58.3 ± 6.8 years (range: 43-74 years old); 95 (76%) were female and 30 (24%) were male. The average hip-knee-ankle (HKA) angle for measuring varus deformity was 7.6° ± 2.4° (range: 5.0-14.2°). In second-look arthroscopy, the status of medial femoral condyle (MFC) cartilage was as follows: 73 (58.4%) patients with ICRS grade I, 37 (29.6%) with ICRS grade II, and 15 (12%) with ICRS grade III. No patients were staged with ICRS grade IV. Additionally, the scores [except International Knee Documentation Committee (IKDC) at 1 year] of the ICRS grade I group improved more significantly than those of the ICRS grade II and III groups., Conclusion: Implantation of hUCB-MSCs with concomitant HTO is an effective treatment for patients with medial compartment osteoarthritis and varus deformity. Regeneration of cartilage improves the clinical outcomes for the patients., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Articular cartilage injury has a poor repair ability and limited regeneration capacity with therapy based on articular chondrocytes (ACs) implantation. Here, we validated the hypothesis that human nasal septum-derived chondrocytes (hNCs) are potent therapeutic agents for clinical use in cartilage tissue engineering using an injectable hydrogel, type I collagen (COL1)., Methods: We manufactured hNCs incorporated in clinical-grade soluble COL1 and investigated their clinical potential as agents in an articular defect model., Results: The hNCs encapsulated in COL1 (hNC-collagen) were uniformly distributed throughout the collagen and showed much greater growth rate than hACs encapsulated in collagen for the 14 days of culture. Fluorescent staining of hNC-collagen showed high expression levels of chondrocyte-specific proteins under clinical conditions. Moreover, a negative mycoplasma screening result were obtained in culture of hNC-collagen. Notably, implantation of hNC-collagen increased the repair of osteochondral defects in rats compared with implantation of collagen only. Many human cells were detected within the cartilage defects., Conclusion: These results provide reliable evidences supporting for clinical applications of hNC-collagen in regenerative medicine for cartilage repair.

Background: Cell-based therapies have been studied for articular cartilage regeneration. Articular cartilage defects have little treatments because articular cartilage was limited regenerative capacity. Damaged articular cartilage is difficult to obtain a successful therapeutic effect. In additionally these articular cartilage defects often cause osteoarthritis. Chondrocyte implantation is a widely available therapy used for regeneration of articular cartilage because this tissue has poor repair capacity after injury. Human nasal septum-drived chondrocytes (hNCs) from the septum show greater proliferation ability and chondrogenic capacity than human articular chondrocytes (hACs), even across different donors with different ages. Moreover, the chondrogenic properties of hNCs can be maintained after extensive culture expansion., Methods: In this study, 2 dimensional (2D) monolayer cultured hNCs (hNCs-2D) and 3 dimensional (3D) spheroids cultured hNCs (hNCs-3D) were examined for chondrogenic capacity in vitro by PCR and immunofluorescence staining for chondrogenic marker, cell survival during cultured and for cartilage regeneration ability in vivo in a rat osteochondral defect model., Results: hNCs-3D showed higher viability and more uniform morphology than 3D spheroids cultured hACs (hACs-3D) in culture. hNCs-3D also showed greater expression levels of the chondrocyte-specific marker Type II collagen (COL2A1) and sex-determining region Y (SRY)-box 9 (SOX9) than hNCs-2D. hNCs-3D also expressed chondrogenic markers in collagen. Specially, in the osteochondral defect model, implantation of hNCs-3D led to greater chondrogenic repair of focal cartilage defects in rats than implantation of hNCs-2D., Conclusion: These data suggest that hNCs-3D are valuable therapeutic agents for repair and regeneration of cartilage defects.

Introduction: Clinical outcomes after the implantation of allogenic human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in osteoarthritic knees have been rarely reported. Our study aimed to investigate clinical outcomes of osteoarthritic patients who underwent hUCB-MSC implantation., Methods: In this case series (level of evidence: 4), from January 2014 to December 2015, 128 patients with full-thickness cartilage lesions (International Cartilage Repair Society grade 4 and Kellgren-Lawrence grade ≤3) who underwent hUCB-MSC implantation were retrospectively evaluated with a minimum of 2-year follow-up. After removing the sclerotic subchondral bone with an arthroscopic burr, 4-mm-diameter holes were created at 2-mm intervals, and hyaluronic acid and hUCB-MSCs were subsequently mixed and implanted in the holes and other articular defect sites.Clinical outcomes were evaluated preoperatively, 1 year postoperatively, and 2 years postoperatively (minimum) using visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC) scores. To assess clinical outcomes, patients were divided into two or three groups according to the lesion size, lesion location, number of lesions, body mass index, and age; statistical analyses were performed using these data., Results: The mean (±standard deviation) VAS, WOMAC, and IKDC scores at 1 and 2 years after surgery including hUCB-MSC implantation improved significantly compared to the preoperative scores ( P  < 0.001). There were significant differences in the lesion location ( P  < 0.05). Medial femoral condyle lesions resulted in worse outcomes compared with lateral femoral condyle and trochlea lesions. No adverse reactions or postoperative complications were noted., Conclusions: Implantation of hUCB-MSCs is effective for treating knee osteoarthritis based on a follow-up lasting a minimum of 2 years., (© 2020 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Purpose: High fibular osteotomy (HFO) is a simple surgical technique to reduce pain and improve function in patients with osteoarthritis via fibular osteotomy. We report short-term results of HFO and mesenchymal cell induced chondrogenesis (MCIC) for the treatment of osteoarthritis of knee with varus deformity., Patients and Methods: 45 symptomatic patients with 14 males and 31 females age ranging from 40 to 75 years were treated by HFO and MCIC. Main lesions involved medial compartment of knee and lateral compartment with normal to mild lesions of lateral meniscus and articular cartilage, amenable to treatment via partial meniscectomy or observation., Results: Knee injury and Osteoarthritis Outcome score and Lysholm showed a statistically significant increase and VAS, varus angle in X-ray showed a statistically significant decrease. A statistically significant difference between preoperative and postoperative scores was detected in male and female patients without any sexual differences., Conclusion: High fibular osteotomy and mesenchymal cell induced chondrogenesis can be considered as a good treatment option for medial compartment osteoarthritis of knee with varus deformity.

Degenerative and traumatic articular cartilage defects are common, difficult to treat, and progressive lesions that cause significant morbidity in the general population. There have been multiple approaches to treat such lesions, including arthroscopic debridement, microfracture, multiple drilling, osteochondral transplantation and autologous chondrocyte implantation (ACI) that are currently being used in clinical practice. Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC) is a single-staged arthroscopic procedure. This method combines a modified microfracture technique with the application of a bone marrow aspirate concentrate (BMAC), hyaluronic acid and fibrin gel to treat articular cartilage defects. We reviewed the current literatures and surgical techniques for mesenchymal cell induced chondrogenesis.

The defects of articular cartilage in the knee joint are a common degenerative disease and currently there are several established techniques to treat this problem, each with their own advantages and shortcomings. Autologous chondrocyte implantation is the current gold standard but the technique is expensive, time-consuming and most versions require two stage procedures and an arthrotomy. Autologous collagen induced chondrogenesis (ACIC) is a single-stage arthroscopic procedure and we developed. This method uses microfracture technique with atelocollagen mixed with fibrin gel to treat articular cartilage defects. We introduce this ACIC techniques and its scientific background.

Healthy and high quality of life has become the main issue with increasing human life span. Many biological treatments for osteoarthritis of the knee have been tried with limited success. We compared data from 7 patients who underwent total knee arthroplasty and 46 patients who underwent autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC) for osteoarthritis of grade IV of the Kellgren-Lawrence classification and grade IV of modified Outerbridge classification from 50 to 65 years of age. Clinical evaluation of the 2 groups showed significant improvement in the mean telephone Knee Society Scoring system (tKSS)-A (pain) and tKSS-B (function) scores throughout the postoperative follow-up period. There was no difference in the patients' satisfaction between the 2 groups. MCIC is a treatment option at least for delaying disease progression of osteoarthritis of the knee., Electronic Supplementary Material: Supplementary material is available for this article at 10.1007/s13770-016-9125-y and is accessible for authorized users.

Rheumatoid arthritis (RA) is an autoimmune disease with chronic and excessive inflammation. Upregulation of interleukin (IL)-17 is involved in the pathogenesis of RA. STX0119 is a specific inhibitor of signal transducer and activator of transcription 3 (STAT3) as a potential target for the treatment of RA. STAT3 is a member of DNA-binding molecules that regulates the expression of proinflammatory cytokines involved in the pathogenesis of RA. The objective of this study was to determine whether STX0119 could inhibit STAT3 and IL-17. We demonstrated that STX0119 decreased T helper (Th) 17 differentiation and IL-17 expression in vitro . STX0119 also improved the severity of zymosan induced arthritis and reduced joint inflammation. STX0119 reduced the proliferation of Th17 and phosphorylated STAT3 expression while increasing Treg differentiation and phosphorylated STAT5 expression. Moreover, STX0119 decreased the expression of IL-6 and -17 but not IL-10. These findings suggest that STX0119 can be used to treat autoimmune RA through inhibiting the activation of STAT3.

We study the efficacy of bone regeneration by using two differently sized allogeneic cancellous bone granules loaded with autologous cultured osteoblasts in a rabbit model. Critical-sized bone defects of the radial shaft were made in 40 New Zealand White rabbits. Small allogeneic bone granules (150-300 μm in diameter) loaded with cultured differentiated autologous osteoblasts were implanted into one forearm (SBG group) and large bone granules (500-710 μm) loaded with osteoblasts were implanted into the forearm of the other side (LBG group). Radiographic evaluations were performed at 3, 6, 9 and 12 weeks and histology and micro-CT image analysis were carried out at 6 and 12 weeks post-implantation. On radiographic evaluation, the LBG group showed a higher bone quantity index at 3 and 6 weeks post-implantation (P < 0.05) but statistical significance was lost at 9 and 12 weeks. The progression of biological processes of the SBG group was faster than that of the LBG group. On micro-CT image analysis, the LBG group revealed a higher total bone volume and surface area than the SBG group at 6 weeks (P < 0.05) but the difference decreased at 12 weeks and was without statistical significance. Histological evaluation also revealed faster progression of new bone formation and maturation in the SBG group. Thus, the two differently sized allogeneic bone granules loaded with co-cultured autologous osteoblasts show no differences in the amount of bone regeneration, although the SBG group exhibits faster progression of bone regeneration and remodeling. This method might therefore provide benefits, such as a short healing time and easy application in an injectable form, in a clinical setting.

Objective: A novel single-stage approach using arthroscopic microdrilling and atelocollagen/fibrin-gel application is employed for cartilage repair of the knee. The purpose of our study was to investigate the morphological and biochemical MRI outcome after this technique., Materials and Methods: A retrospective case series of ten patients (mean age 45 years) with symptomatic chondral defects in the knee who were treated arthroscopically with microdrilling and atelocollagen application was analyzed. All defects were ICRS grade III or IV and the sizes were 2-8 cm(2) intra-operatively. All patients underwent morphological MRI and T2-star mapping at 1.5 T at 1-year follow-up. The magnetic resonance observation of cartilage repair tissue (MOCART) score was assessed. T2* relaxation time values of repair tissue and a healthy native cartilage area was assessed by means of region of interest analysis on the T2* maps., Results: The mean MOCART score at 1-year follow-up was 71.7 ± 21.0 ranging from 25 to 95. The mean T2* relaxation times were 30.6 ± 11.3 ms and 28.8 ± 6.8 ms for the repair tissue and surrounding native cartilage, respectively. The T2* ratio between the repair tissue and native cartilage was 105%  ± 30%, indicating repair tissue properties similar to native cartilage., Conclusions: An arthroscopic single-stage procedure using microdrilling in combination with atelocollagen gel and fibrin-glue can provide satisfactory MRI results at 1-year follow-up, with good cartilage defect filling. The T2* values in the repair tissue achieved similar values compared to normal hyaline cartilage.

Background: [corrected] To develop a successful treatment modality for osteonecrosis, an appropriate animal model is essential. We have proposed a new osteonecrosis model that shows the total amount of necrosis and in which we observed new bone formation after transplanting autologous cultured osteoblasts., Materials and Methods: The femoral condyles of the right knees of New Zealand white rabbits were exposed after dissecting the ligaments surrounding the distal femur. After which, the metaphyseal-diaphyseal junction was cut using a saw, and the entire femoral condyle was isolated. After three liquid nitrogen treatments, the isolated femoral condyle was internally fixated to the femoral shaft using two or three Kirschner wires. Bone marrow isolated from the iliac crest was cultivated to differentiate it into osteoblasts, and the cultured cells were then injected into the necrotic bone., Results: Viable osteocytes with well-stained nuclei were not present in the necrotic areas at any stage of the development of the osteonecrosis model within 24 wk after osteonecrosis induction. However, new bone formation with osteocytes and blood vessels was observed in the necrotic bone 12 wk after transplanting the autologous cultured osteoblasts., Conclusions: The distal femoral condyle of the rabbit is an appropriate model for demonstrating osteonecrosis and treatment evaluation owing to its easy reproducibility and treatment interpretation. Therefore, autologous cultured osteoblast treatment would seem to be a potentially successful treatment modality for osteonecrosis., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Nine patients aged over 8 years with developmental dislocation of the hip were treated by an open reduction, femoral shortening and varus derotation osteotomy with or without a Chiari osteotomy. The mean age of the patients was 11.1 years (range 8-17 years), and the mean follow-up period was 7.1 years (range 1-13 years). The left hip was involved in four cases: the right in three and two cases were bilateral. One hip redislocated. The remaining patients recovered nearly full movement of the affected hip. Five out of eight patients had a normal gait without limping or pain. Two others limped secondary to a leg-length discrepancy, which was corrected with leg equalization. The remaining patient had an improvement of her preoperative limp and was pain-free. These results indicate that it is possible to obtain good hip function after open reduction of a developmentally dislocated hip, even after the age of 8 years.