Bilateral pyogranulomatous otitis externa with putative cartilage destruction in a dog: A severe case of auricular chondritis?

Auricular chondritis of unknown cause was suspected in a 10-year-old male Bolognese dog with a five-month history of painful bilateral nodular and ulcerative pyogranulomatous dermatitis of the pinnae with putative auricular cartilage destruction. Pain and lesions resolved with immunosuppressive doses of prednisolone, yet the condition resulted in deformity of both pinnae and external canals.

Une chondrite auriculaire d'étiologie inconnue est suspectée chez un bichon bolonais mâle de 10 ans qui présente depuis 5 mois une dermatite pyogranulomateuse nodulaire et ulcéreuse bilatérale douloureuse du pavillon de l'oreille avec une destruction présumée du cartilage auriculaire. La douleur et les lésions disparaissent avec des doses immunosuppressives de prednisolone, mais l'affection entraîne une déformation des deux pavillons et des conduits auriculaires externes.

Suspeitou­se de condrite auricular de causa desconhecida em um cão macho Bolonhês de 10 anos de idade com um histórico de cinco meses de dermatite piogranulomatosa ulcerativa e nodular bilateral no pavilhão auricular com suposta destruição de cartilagem auricular. A dor e as lesões resolveram com doses imunossupressoras de prednisolona apesar de a etiologia ter resultado na deformidade de ambas as orelhas e condutos auditivos.

Se sospechó la existencia de una condritis auricular de causa desconocida en un perro boloñés de 10 años con historia de 5 meses de duración de una dermatitis nodular ulcerativa piogramulomatosa y bilateral en las orejas con posible destrucción del cartílago auricular. El dolor y las lesiones se resolvieron con dosis inmunosupresoras de prednisolona pero la enfermedad produjo deformación de ambas orejas y de los canales auriculares externos.

The Effect of Autologous Adipose-Derived Stromal Vascular Fractions on Cartilage Regeneration Was Quantitatively Evaluated Based on the 3D-FS-SPGR Sequence: A Clinical Trial Study.

BACKGROUND: Numerous reports confirmed the safety and clinical efficacy of autologous adipose-derived stromal vascular fractions (SVF), which have recently been used to treat osteoarthritis (OA). However, there is still no consensus as to whether SVF can promote cartilage regeneration. Herein, the purpose of our study was to evaluate the effectiveness of SVF versus hyaluronic acid (HA) in cartilage regeneration by establishing a cartilage model based on the three-dimensional fat-suppressed spoiled gradient recalled echo (3D-FS-SPGR) sequence. METHODS: Patients with symptomatic OA were recruited in our research, who were randomized into two groups. Meanwhile, patients in Kellgren-Lawrence (K-L) grades 2 and 3 were distinguished in each group. In the test group, patients received SVF injections of the knee, while patients in the control group received the same dose of HA. Each patient underwent the 3D-FS-SPGR sequence to establish a cartilage model at baseline, 6 months, and 12 months, respectively. The cartilage was characterized into six regions, and relevant parameters of the cartilage model were counted. Clinical and radiographic scores were recorded in one-year follow-up. RESULTS: In all regions, the thickness and volume of cartilage defect and the volume of healthy cartilage were improved to some extent in the test group, especially the medial femoral condyle (MF) and medial tibial condyle (MT). In grades 2 and 3, the thickness and volume of cartilage defect decreased by 0.92 ± 0.18 mm and 1.03 ± 0.23 mm and 84.00 ± 32.30 mm3 and 130.30 ± 49.56 mm3 in MF and by 0.96 ± 0.22 mm and 0.99 ± 0.14 mm and 64.18 ± 21.40 mm3 and 95.11 ± 19.93 mm3 in MT, respectively. No such phenomenon was observed in the control group. Meanwhile, the SVF-treated knees showed significant improvement in clinical and radiographic scores at 12 months. Nevertheless, these scores of the control group became worse at 12-month follow-up visit. CONCLUSION: Taken together, this study shows that intra-articular injection of SVF markedly improved the clinical symptoms without adverse events, thereby repairing the damaged articular cartilage through cartilage regeneration.

Auricular Cartilage Resection for Treatment-Refractory Idiopathic Chronic Chondritis: A Case Series.

OBJECTIVE: Describe a series of cases of idiopathic chronic auricular chondritis refractory to antibiotics and steroids treated successfully with surgery. STUDY DESIGN: Case series. SETTING: Two tertiary academic medical centers. PATIENTS: We analyzed four patients diagnosed with chronic auricular deformity, pain, and drainage for a period of 1 to 5 years who had failed prolonged treatment consisting of antibiotics, corticosteroids, and incision and drainage. All four patients were smokers, three were diabetic, and two had a history of bariatric surgery. INTERVENTIONS: Operative subcutaneous partial auriculectomy (removal of diseased cartilage and excess skin) was performed. MAIN OUTCOME MEASURES: Resolution of pain and drainage, need for additional procedures, and reduction in narcotics required for pain control were analyzed. RESULTS: Two of the four patients were given an immediate postoperative course of doxycycline and ciprofloxacin. With a minimum of 6 weeks' follow-up, all four patients had complete resolution of pain and recurrent drainage postoperatively. One patient requiring daily narcotic medication for pain and benzodiazepine for sleep preoperatively no longer required prescription medication. All specimens revealed chronic dermal and cartilage inflammation. Three of four cases had polymicrobial infection. One case had only skin contaminant growth on culture following multiple oral and parental antibiotic regimens. CONCLUSIONS: Surgical excision of diseased cartilage as a result of idiopathic chronic chondritis is an effective treatment in those cases refractory to antibiotics and incision and drainage, and should be considered in the treatment algorithm for similar patients, potentially offering definitive cure.

Hymovis MO.RE. in the treatment of knee and ankle chondropathy in elite athletes: preliminary results of the CHAMPS (Cohort study about HYADD4-G Administration for Pain relief on Soccer players) prospective clinical study.

OBJECTIVE: This study evaluated single intra-articular injections of Hymovis MO.RE., a hyaluronic acid hexadecyl derivative (HYADD4-G), to manage post-traumatic or degenerative knee or ankle chondropathy in professional soccer players. PATIENTS AND METHODS: Twenty-five players affected by knee (n = 12) or ankle (n = 13) chondropathy were prospectively enrolled and treated by two single Hymovis MO.RE. (32 mg/4 ml) injections at the beginning of the football season (V0, baseline) and at mid-season (V1, 19-20 weeks thereafter), and were followed-up until the end of the season (V2, after further 19-20 weeks). Knee cases were evaluated using the 2000 IKDC knee subjective examination form and the modified Lysholm scoring system. Ankle cases were evaluated using the American Orthopaedic Foot Ankle Society (AOFAS) ankle-hindfoot score. Patients were also evaluated using a VAS Likert scale and a four-category scale recording both the patient's and the doctor's assessment on joint mobility in degrees and overall treatment efficacy. Adverse events, patient withdrawals and local reaction to injections were also assessed. RESULTS: In knee patients, the 2000 IKDC subjective score improved from 46.8 ± 11.4 at V0 to 83.1 ± 12.5 at V2. Their modified Lysholm score improved from 58.8 ± 8.9 at V0 to 90.6 ± 8.3 at V2. In the ankle patients, the AOFAS score improved from 52.2 ± 5.6 at V0 to 96.4 ± 4.5 at V2. VAS Likert values and subjective evaluations improved at V1 and were maintained at V2. No side effects were recorded. CONCLUSIONS: A single Hymovis MO.RE. (32 mg/4 ml) intra-articular injection, repeated after 19-20 weeks, may be a viable option to improve symptoms and function in professional soccer players suffering from knee and ankle chondropathy.

Calcium chelator BAPTA­AM protects against iron overload­induced chondrocyte mitochondrial dysfunction and cartilage degeneration.

Osteoarthritis (OA) is a common joint disease that is characterized by cartilage degradation. Iron deposition in the joints is common during the pathogenic progression of OA and recent studies have indicated that iron overload is an important contributor to OA progression. Calcium chelators have been reported to inhibit iron influx via modulating transferrin receptor protein 1 internalization, and they have been identified as a potential approach to the treatment of iron overload­induced diseases. The aim of the present study was to investigate the effect of calcium chelators on the progression of iron overload­induced OA. Primary chondrocytes were treated with various concentrations of ferric ammonium citrate (FAC) to mimic iron overload in vitro, followed by co­treatment with the calcium chelator BAPTA acetoxymethyl ester (BAPTA­AM). Subsequently, intracellular iron levels, cell viability, reactive oxygen species (ROS) levels, mitochondrial function and morphological changes, as well as MMP levels, were detected using commercial kits. It was demonstrated that FAC treatment significantly promoted chondrocyte apoptosis and the expression of MMPs, and these effects were reversed by co­treatment with BAPTA­AM. Moreover, BAPTA­AM suppressed iron influx into chondrocytes and inhibited iron overload­induced ROS production and mitochondrial dysfunction. These results indicated that calcium chelators may be of value in the treatment of iron metabolism­related diseases and iron overload­induced OA progression.

Study on the potential active components and molecular mechanism of Xiao Huoluo Pills in the treatment of cartilage degeneration of knee osteoarthritis based on bioinformatics analysis and molecular docking technology.

BACKGROUND: Knee osteoarthritis is a common joint degenerative disease. Xiao Huoluo Pills (XHLP) has been used to treat degenerative diseases such as osteoarthritis and hyperosteogeny. However, XHLP's specific effective ingredients and mechanism of action against osteoarthritis have not been explored. Therefore, bioinformatics technology and molecular docking technology are employed in this study to explore the molecular basis and mechanism of XHLP in the treatment of knee osteoarthritis. METHODS: Public databases (TCMSP, Batman-TCM, HERB, DrugBank, and UniProt) are used to find the effective active components and corresponding target proteins of XHLP (screening conditions: OB > 30%, DL ≥ 0.18). Differentially expressed genes related to cartilage lesions of knee osteoarthritis are obtained based on the GEO database (screening conditions: adjust P value < 0.01, |log2 FC|≥1.0). The Venn package in R language and the BisoGenet plug-in in Cytoscape are adopted to predict the potential molecules of XHLP in the treatment of knee osteoarthritis. The XHLP-active component-target interaction network and the XHLP-knee osteoarthritis-target protein core network are constructed using Cytoscape software. Besides, GO/KEGG enrichment analysis on core genes is performed using the Bioconductor package and clusterProfiler package in the R language to explain the biological functions and signal pathways of the core proteins. Finally, molecular docking is performed through software such as Vina, LeDock, Discovery Studio 2016, PyMOL, AutoDockTools 1.5.6, so as to verify the binding ability between the active components of the drug and the core target protein. RESULTS: XHLP has been screened out of 71 potentially effective active compounds for the treatment of OA, mainly including quercetin, Stigmasterol, beta-sitosterol, Izoteolin, and ellagic acid. Knee osteoarthritis cartilage lesion sequencing data (GSE114007) was screened out of 1672 differentially expressed genes, including 913 upregulated genes and 759 downregulated genes, displayed as heat maps and volcano maps. Besides, 33 core target proteins are calculated by Venn data package in R and BisoGenet plug-in in Cytoscape. The enrichment analysis on these target genes revealed that the core target genes are mainly involved in biological processes such as response to oxygen levels, mechanical stimulus, vitamin, drug, and regulation of smooth muscle cell proliferation. These core target genes are involved in signaling pathways related to cartilage degeneration of knee osteoarthritis such as TNF signaling pathway and PI3K-Akt signaling pathway. Finally, the molecular docking verification demonstrates that some active components of the drug have good molecular docking and binding ability with the core target protein, further confirming that XHLP has the effect of inhibiting cartilage degeneration in knee osteoarthritis. CONCLUSIONS: In this study, based on the research foundation of bioinformatics and molecular docking technology, the active components and core target molecules of XHLP for the treatment of cartilage degeneration of knee osteoarthritis are screened out, and the potential mechanism of XHLP inhibiting cartilage degeneration of knee osteoarthritis is deeply explored. The results provide theoretical basis and new treatment plan for XHLP in the treatment of knee osteoarthritis.

The Hexosamine Biosynthetic Pathway as a Therapeutic Target after Cartilage Trauma: Modification of Chondrocyte Survival and Metabolism by Glucosamine Derivatives and PUGNAc in an Ex Vivo Model.

The hexosamine biosynthetic pathway (HBP) is essential for the production of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), the building block of glycosaminoglycans, thus playing a crucial role in cartilage anabolism. Although O-GlcNAcylation represents a protective regulatory mechanism in cellular processes, it has been associated with degenerative diseases, including osteoarthritis (OA). The present study focuses on HBP-related processes as potential therapeutic targets after cartilage trauma. Human cartilage explants were traumatized and treated with GlcNAc or glucosamine sulfate (GS); PUGNAc, an inhibitor of O-GlcNAcase; or azaserine (AZA), an inhibitor of GFAT-1. After 7 days, cell viability and gene expression analysis of anabolic and catabolic markers, as well as HBP-related enzymes, were performed. Moreover, expression of catabolic enzymes and type II collagen (COL2) biosynthesis were determined. Proteoglycan content was assessed after 14 days. Cartilage trauma led to a dysbalanced expression of different HBP-related enzymes, comparable to the situation in highly degenerated tissue. While GlcNAc and PUGNAc resulted in significant cell protection after trauma, only PUGNAc increased COL2 biosynthesis. Moreover, PUGNAc and both glucosamine derivatives had anti-catabolic effects. In contrast, AZA increased catabolic processes. Overall, "fueling" the HBP by means of glucosamine derivatives or inhibition of deglycosylation turned out as cells and chondroprotectives after cartilage trauma.

Chondroprotective Effects of a Histone Deacetylase Inhibitor, Panobinostat, on Pain Behavior and Cartilage Degradation in Anterior Cruciate Ligament Transection-Induced Experimental Osteoarthritic Rats.

Osteoarthritis (OA) is the most common articular degenerative disease characterized by chronic pain, joint inflammation, and movement limitations, which are significantly influenced by aberrant epigenetic modifications of numerous OA-susceptible genes. Recent studies revealed that both the abnormal activation and differential expression of histone deacetylases (HDACs) might contribute to OA pathogenesis. In this study, we investigated the chondroprotective effects of a marine-derived HDAC inhibitor, panobinostat, on anterior cruciate ligament transection (ACLT)-induced experimental OA rats. The intra-articular administration of 2 or 10 µg of panobinostat (each group, n = 7) per week from the 6th to 17th week attenuates ACLT-induced nociceptive behaviors, including secondary mechanical allodynia and weight-bearing distribution. Histopathological and microcomputed tomography analysis showed that panobinostat significantly prevents cartilage degeneration after ACLT. Moreover, intra-articular panobinostat exerts hypertrophic effects in the chondrocytes of articular cartilage by regulating the protein expressions of HDAC4, HDAC6, HDAC7, runt-domain transcription factor-2, and matrix metalloproteinase-13. The study indicated that HDACs might have different modulations on the chondrocyte phenotype in the early stages of OA development. These results provide new evidence that panobinostat may be a potential therapeutic drug for OA.

Intralesional Hyaluronic Acid Injection for Chondrodermatitis Nodularis Helicis: A Novel Treatment for Rapid Relief of Pain and Healing of Ulcerations.

BACKGROUND: Chondrodermatitis nodularis helicis (CNH) is a common chronic condition characterized by a tender nodule on the helix or antihelix of the ear which may or may not have accompanying crusting, scaling, or ulceration and that is often difficult to treat. OBJECTIVE: Develop an easy, effective, and durable treatment to reduce the pain and clinical signs including ulcerations associated with CNH using injectable hyaluronic acid (HA). MATERIALS AND METHODS: Twenty-four patients were injected and followed up in 2 to 4 weeks intervals using 0.2 to 0.3 mL of various HA with a high G-Prime. RESULTS: Injectable HA significantly improved the symptoms and also the clinical appearance of all patients treated after 1 or 2 injections except 1 patient. Extrusion of the material through a preexisting ulcer usually required a second follow-up injection 2 weeks later. No adverse events were noted with the injections other than the intentional visible bulging of the injected region with HA. CONCLUSION: Injectable HA provides almost immediate relief from the discomfort of CNH in most cases in less than 1 or 2 weeks, significantly improves the clinical appearance over time and resolves accompanying ulcerations.

Intra-Articular Atelocollagen Injection for the Treatment of Articular Cartilage Defects in Rabbit Model.

BACKGROUND: Atelocollagen is widely recognized as a biomaterial for regenerative medicine because of its good compatibility and low antigenicity. Injury of the outermost layer of articular cartilage, known as the lamina splendens, can lead to osteoarthritis (OA) and eventually full-thickness cartilage loss. The intra-articular injection of atelocollagen has been designed to restore the cartilage layer and cartilage defects in OA joints. In this study, we investigated the efficacy of atelocollagen as a cartilage supplement for joint defects. METHODS: In this study, we evaluated the therapeutic effects of atelocollagen in animals with cartilage defects. Femoral groove defects were artificially created in 12 male New Zealand white rabbits, which were treated with intra-articular injection of either atelocollagen (experimental) or normal saline (control). The results were observed 3, 6, 9, and 12 weeks following macroscopic and histological evaluations. RESULTS: At 3 weeks, cartilage tissue was restored in the experimental group, whereas the control group did not show signs of restoration. At 12 weeks, defects in both groups were filled with regenerated tissue, but the experimental group displayed a morphologically better appearance. Histologically, the regenerated tissue in the experimental group showed statistically significant improvement compared to the control group, with a structure similar to that of normal articular cartilage. CONCLUSION: The results showed that the intra-articular injection of atelocollagen enhanced cartilage regeneration following rabbit patellar groove defects. Therefore, intra-articular injection of atelocollagen can be used as an effective supplement for joint defects.

Effect of Systemic Administration of Granulocyte Colony-Stimulating Factor on a Chronic Partial-Thickness Cartilage Defect in a Rabbit Knee Joint.

OBJECTIVE: Cartilage lesions in the knee joint can lead to joint mechanics changes and cause knee pain. Bone marrow stimulation (BMS) promotes cartilage regeneration by perforating the subchondral bone just below the injury and inducing bone marrow cells. This study aimed to investigate whether systemic administration of granulocyte colony-stimulating factor (G-CSF) with BMS improves repair of chronic partial-thickness cartilage defects (PTCDs). DESIGN: Eighteen 6-month-old New Zealand white rabbits were divided into 3 groups: control (C, n = 6), BMS alone (n = 6), and BMS + G-CSF (n = 6). Partial cartilage defects with 5 mm diameter were created in the trochlear region of both knees; after 4 weeks, the BMS alone and BMS + G-CSF groups underwent BMS; G-CSF (50 µg/kg) or saline was administered subcutaneously for 5 days starting from 3 days before BMS. At 8 and 16 weeks after cartilage defect creation, the area of cartilage defects was macroscopically and histologically evaluated. RESULTS: International Cartilage Repair Society (ICRS) grades for macroscopic assessment were 0, 0.7, and 0.7 at 8 weeks and 0, 1.2, and 1.3 at 16 weeks in the C, BMS, and BMS + G-CSF groups, respectively. Wakitani scores for histological assessment were 9.8, 8.7, and 8.2 at 8 weeks and 9.5, 9, and 8.2 at 16 weeks in the C, BMS, and BMS + G-CSF groups, respectively. The BMS + G-CSF group showed significantly more repair than the C group, but there was no difference from the BMS group. CONCLUSIONS: The effect of BMS and G-CSF on chronic PTCDs in mature rabbit knees was limited.

Therapeutic Prospects of Cannabinoids in the Immunomodulation of Prevalent Autoimmune Diseases.

Introduction: Cannabinoids such as ▵-9-THC and CBD can downregulate the immune response by modulating the endocannabinoid system. This modulation is relevant for the treatment of prevalent autoimmune diseases (ADs), such as multiple sclerosis (MS), systemic lupus erythematosus (SLE), diabetes mellitus type 1 (DMT1), and rheumatoid arthritis (RA). These conditions require new therapeutic options with fewer side effects for the control of the autoimmune response. Objective: to conduct a literature review of preclinical scientific evidence that supports further clinical investigations for the use of cannabinoids (natural or synthetic) as potential immunomodulators of the immune response in ADs. Methodology: A systematic search was carried out in different databases using different MeSH terms, such as Cannabis sativa L., cannabinoids, immunomodulation, and ADs. Initially, 677 journal articles were found. After filtering by publication date (from 2000 to 2020 for SLE, DMT1, and RA; and 2010 to 2020 for MS) and removing the duplicate items, 200 articles were selected and analyzed by title and summary associated with the use of cannabinoids as immunomodulatory treatment for those diseases. Results: Evidence of the immunomodulatory effect of cannabinoids in the diseases previously mentioned, but SLE that did not meet the search criteria, was summarized from 24 journal articles. CBD was found to be one of the main modulators of the immune response. This molecule decreased the number of Th1 and Th17 proinflammatory cells and the production of the proinflammatory cytokines, interleukin (IL)-1, IL-12, IL-17, interferon (IFN)-γ, and tumor necrosis factor alpha, in mouse models of MS and DMT1. Additionally, new synthetic cannabinoid-like molecules, with agonist or antagonist activity on CB1, CB2, TRPV1, PPAR-α, and PPAR-γ receptors, have shown anti-inflammatory properties in MS, DMT1, and RA. Conclusion: Data from experimental animal models of AD showed that natural and synthetic cannabinoids downregulate inflammatory responses mediated by immune cells responsible for AD chronicity and progression. Although synthetic cannabinoid-like molecules were evaluated in just two clinical trials, they corroborated the potential use of cannabinoids to treat some ADs. Notwithstanding, new cannabinoid-based approaches are required to provide alternative treatments to patients affected by the large group of ADs.

Growth differentiation factor 5 in cartilage and osteoarthritis: A possible therapeutic candidate.

Growth differentiation factor 5 (GDF-5) is essential for cartilage development and homeostasis. The expression and function of GDF-5 are highly associated with the pathogenesis of osteoarthritis (OA). OA, characterized by progressive degeneration of joint, particularly in cartilage, causes severe social burden. However, there is no effective approach to reverse the progression of this disease. Over the past decades, extensive studies have demonstrated the protective effects of GDF-5 against cartilage degeneration and defects. Here, we summarize the current literature describing the role of GDF-5 in development of cartilage and joints, and the association between the GDF-5 gene polymorphisms and OA susceptibility. We also shed light on the protective effects of GDF-5 against OA in terms of direct GDF-5 supplementation and modulation of the GDF-5-related signalling. Finally, we discuss the current limitations in the application of GDF-5 for the clinical treatment of OA. This review provides a comprehensive insight into the role of GDF-5 in cartilage and emphasizes GDF-5 as a potential therapeutic candidate in OA.

Intra-articular Injection of Type I Atelocollagen to Alleviate Knee Pain: A Double-Blind, Randomized Controlled Trial.

OBJECTIVE: Collagen disruption is one of the underlying causes of knee pain in patients with osteoarthritis and/or diverse cartilage defects. Atelocollagen is a type of collagen that lacks telopeptides and thus has reduced antigenicity. The intra-articular injection of type I atelocollagen supplements collagen levels in the disrupted articular cartilage. This randomized controlled trial evaluated the effects of the intra-articular injection of atelocollagen for the management of knee pain. DESIGN: Two hundred patients with osteoarthritis, chondromalacia, or other cartilage defects were randomly assigned to receive a 3-mL intra-articular injection of atelocollagen (BioCollagen group) or saline (Placebo group). Clinical improvement was evaluated over a 24-week period using the 100-mm visual analogue scale (VAS), the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and the 36-item Short-Form Health Survey (SF-36). RESULTS: VAS scores were significantly better in the BioCollagen group as compared with the Placebo group at 24 weeks. More patients in the BioCollagen group reported exceeding 20% and 40% VAS improvements. The WOMAC and SF-36 scores were also significantly improved from baseline after the intra-articular injection of atelocollagen; although, the differences between the BioCollagen and Placebo groups were not significant. There were no unexpected or severe adverse events reported for either group. CONCLUSIONS: The results show that an intra-articular injection of atelocollagen effectively alleviates knee pain, as intended. Therefore, the intra-articular injection of atelocollagen can be considered an alternative solution to controlling knee pain due to osteoarthritis and diverse cartilage defects.

The Effect of Intraarticular Insulin on Chondral Defect Repair.

OBJECTIVE: The aim of this study is to evaluate the effects of intraarticular insulin on the treatment of chondral defects. DESIGN: Twenty-four mature New Zealand rabbits were randomly divided into 3 groups as control (Group 1), microfracture (Group 2), and microfracture and insulin (Group 3). Four-millimeter full-thickness cartilage defects were created to the weight-bearing surface on the medial femoral condyles of each rabbit. In the first group, any additional interventions were not performed. Microfracture was performed on defects in groups 2 and 3. Additionally, 10 IU of insulin glargine was administrated into the knee joints of the third group. Three months after surgery, the knee joints were harvested and cartilage quality was assessed according to Wakitani and ICRS (International Cartilage Repair Society) scores histopathologically. Insulin injections were performed into the knees of 2 additional rabbits without creating a cartilage defect to evaluate the potential adverse effects of insulin on healthy cartilage (Group 4). RESULTS: The total ICRS and Wakitani scores of the insulin group were found to be significantly lower than the microfracture group but similar to the control group. No negative effects of insulin on healthy cartilage were detected. Intraarticular insulin after surgery has led to a statistically significant decrease in systemic blood sugar levels whereas the decrease observed after administration to intact tissues was not statistically significant. CONCLUSIONS: Insulin had a negative influence on the quality of cartilage regeneration and had no effect on healthy cartilage. Intraarticular insulin administration does not cause significant systemic effects in intact tissue.

Diagnosis and clinical management of auricular chondritis in a dog presenting for evaluation of severe pain.

BACKGROUND: The aetiology and appropriate treatment for auricular chondritis in the dog are currently unclear. This report describes a unique presentation and successful treatment of a dog with auricular chondritis. CLINICAL SUMMARY: A 12-year-old, female spayed, Labrador retriever dog was presented for severe pain thought to be neurological in origin. The pain was located to the right pinna and two punch biopsies were acquired and evaluated, revealing lymphoplasmacytic to pyogranulomatous inflammation involving the auricular cartilage with no infectious agents. Treatment with systemic oral prednisone resulted in resolution of clinical signs within four weeks of initiation of treatment. The dog remained free of clinical signs for six months following discontinuation of treatment before being euthanized for an unrelated reason. CONCLUSIONS: Further evaluation of canine auricular chondritis is needed, yet pain may be a prominent finding; monotherapy with systemic prednisone may provide quick and complete resolution of clinical sysmptoms.

Emerging pharmaceutical therapies for osteoarthritis.

The prevalence of osteoarthritis (OA) and the burden associated with the disease are steadily increasing worldwide, representing a major public health challenge for the coming decades. The lack of specific treatments for OA has led to it being recognized as a serious disease that has an unmet medical need. Advances in the understanding of OA pathophysiology have enabled the identification of a variety of potential therapeutic targets involved in the structural progression of OA, some of which are promising and under clinical investigation in randomized controlled trials. Emerging therapies include those targeting matrix-degrading proteases or senescent chondrocytes, promoting cartilage repair or limiting bone remodelling, local low-grade inflammation or Wnt signalling. In addition to these potentially disease-modifying OA drugs (DMOADs), several targets are being explored for the treatment of OA-related pain, such as nerve growth factor inhibitors. The results of these studies are expected to considerably reshape the landscape of OA management over the next few years. This Review describes the pathophysiological processes targeted by emerging therapies for OA, along with relevant clinical data and discussion of the main challenges for the further development of these therapies, to provide context for the latest advances in the field of pharmaceutical therapies for OA.

Exquisite design of injectable Hydrogels in Cartilage Repair.

Cartilage damage is still a threat to human beings, yet there is currently no treatment available to fully restore the function of cartilage. Recently, due to their unique structures and properties, injectable hydrogels have been widely studied and have exhibited high potential for applications in therapeutic areas, especially in cartilage repair. In this review, we briefly introduce the properties of cartilage, some articular cartilage injuries, and now available treatment strategies. Afterwards, we propose the functional and fundamental requirements of injectable hydrogels in cartilage tissue engineering, as well as the main advantages of injectable hydrogels as a therapy for cartilage damage, including strong plasticity and excellent biocompatibility. Moreover, we comprehensively summarize the polymers, cells, and bioactive molecules regularly used in the fabrication of injectable hydrogels, with two kinds of gelation, i.e., physical and chemical crosslinking, which ensure the excellent design of injectable hydrogels for cartilage repair. We also include novel hybrid injectable hydrogels combined with nanoparticles. Finally, we conclude with the advances of this clinical application and the challenges of injectable hydrogels used in cartilage repair.

Preparation of high precision multilayer scaffolds based on Melt Electro-Writing to repair cartilage injury.

Rationale: Articular cartilage injury is quite common. However, post-injury cartilage repair is challenging and often requires medical intervention, which can be aided by 3D printed tissue engineering scaffolds. Specifically, the high accuracy of Melt Electro-Writing (MEW) technology facilitates the printing of scaffolds that imitate the structure and composition of natural cartilage to promote repair. Methods: MEW and Inkjet printing technology was employed to manufacture a composite scaffold that was then implanted into a cartilage injury site through microfracture surgery. While printing polycaprolactone (PCL) or PCL/hydroxyapatite (HA) scaffolds, cytokine-containing microspheres were sprayed alternately to form multiple layers containing transforming growth factor-ß1 and bone morphogenetic protein-7 (surface layer), insulin-like growth factor-1 (middle layer), and HA (deep layer). Results: The composite biological scaffold was conducive to adhesion, proliferation, and differentiation of mesenchymal stem cells recruited from the bone marrow and blood. Meanwhile, the environmental differences between the scaffold's layers contributed to the regional heterogeneity of chondrocytes and secreted proteins to promote functional cartilage regeneration. The biological effect of the composite scaffold was validated both in vitro and in vivo. Conclusion: A cartilage repair scaffold was established with high precision as well as promising mechanical and biological properties. This scaffold can promote the repair of cartilage injury by using, and inducing the differentiation and expression of, autologous bone marrow mesenchymal stem cells.

Intra-articular Injections of Hyaluronic Acid on Osteochondral Lesions of the Talus After Failed Arthroscopic Bone Marrow Stimulation.

BACKGROUND: The purpose of the study was to compare clinical and functional outcomes before and after hyaluronic acid (HA) injections in patients with osteochondral lesions of the talus who experienced a failure of their primary treatment with arthroscopic microfracture surgery. METHODS: A total of 40 patients were included in the final study. These patients had received microfracture surgery but continued to experience postoperative pain over an average of 13.0 months (range, 0-81 months) and were available for investigation with a mean follow-up for 29.1 months (SD 14.7; range 2.6-79.6 months). All patients received intra-articular injections of HA once per week for 3 weeks. We assessed clinical and functional outcomes before and after injection using the American Orthopaedic Foot & Ankle Society (AOFAS) score, Foot and Ankle Outcome Score (FAOS), Short Form Health Survey (SF-36), the visual analog scale (VAS) for pain, and the Alexander subjective scale. RESULTS: The AOFAS score significantly increased from 50.7 ± 13.8 to 79.9 ± 13.8 and the FAOS scores for symptom, pain, daily living, and sports were significantly higher postinjection compared to preinjection (all P < .001). Similarly, the mean VAS for pain was significantly decreased after 6 weeks following injection and continued to decrease over the follow-up period; the mean VAS was significantly lower postinjection compared to preinjection at 12 months (P < .001). CONCLUSION: Intra-articular HA injections on average significantly improved clinical and functional scores after failed primary operative treatment. HA injections may provide an alternative to secondary operative treatment and provide better clinical outcomes than other conservative treatments. LEVEL OF EVIDENCE: Level II, prospective observational cohort study.