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Background: The aim of this study was to investigate the therapeutic effects and mechanisms of PRP-exos combined with cyclic peptide-modified β-TCP scaffold in the treatment of rabbit knee cartilage defect. Methods: PRP-exos were extracted and characterized by TEM, NTA and WB. The therapeutic effects were evaluated by ICRS score, HE staining, Immunohistochemistry, qRT-PCR and ELISA. The repair mechanism of PRP-exos was estimated and predicted by miRNA sequencing analysis and protein–protein interaction network analysis. Results: The results showed that PRP-exos had a reasonable size distribution and exhibited typical exosome morphology. The combination of PRP-exos and cyclic peptide-modified β-TCP scaffold improved ICRS score and the expression level of COL-2, RUNX2, and SOX9. Moreover, this combination therapy reduced the level of MMP-3, TNF-α, IL-1β, and IL-6, while increasing the level of TIMP-1. In PRP-exos miRNA sequencing analysis, the total number of known miRNAs aligned across all samples was 252, and a total of 91 differentially expressed miRNAs were detected. The results of KEGG enrichment analysis and the protein–protein interaction network analysis indicated that the PI3K/AKT signaling pathway could impact the function of chondrocytes by regulating key transcription factors to repair cartilage defect. Conclusion: PRP-exos combined with cyclic peptide-modified β-TCP scaffold effectively promoted cartilage repair and improved chondrocyte function in rabbit knee cartilage defect. Based on the analysis and prediction of PRP-exos miRNAs sequencing, PI3K/AKT signaling pathway may contribute to the therapeutic effect. These findings provide experimental evidence for the application of PRP-exos in the treatment of cartilage defect. [ABSTRACT FROM AUTHOR]

Objective: Knee osteoarthritis is the most common osteoarthritis and imposes a significant burden on patients' lives. Several treatment methods can promote cartilage repair to varying extents, but there are limited studies on the combined application of different treatments. The purpose of this study is to evaluate the clinical efficacy of microfracture combined with fibrinogen and platelet-rich plasma (PRP) under arthroscopic in treating knee osteoarthritis, so as to provide a basis for clinical treatment decisions. Method: A total of 113 patients with knee osteoarthritis who received orthopedic treatment from January 2021 to June 2022 were selected. They were divided into two groups according to whether they received fibrinogen and PRP treatment in addition to microfracture treatment. The two groups were analyzed to compare the differences in knee joint function and quality of life at different points. Results: The study compared changes in knee joint function scores and quality of life between the two groups after treatment and found that the quality of life of patients in the combined treatment group was significantly better than that of patients who received microfracture only (at 12-month follow-up, EuroQol-VAS scores were 64.32 ± 5.63 for the microfracture group (MFx) and 75.65 ± 8.57 for the fibrinogen combined with platelet-rich plasma-assisted microfracture group (FPRPA MFx); P = 0.015; at 24-month follow-up, EuroQol-VAS scores were 66.47 ± 5.18 for the MFx group and 79.40 ± 7.43 for the FPRPA MFx group, P = 0.022). There was also a strong correlation between patients' quality of life and knee joint function score index (IKDC score correlation coefficient r=-0.375, Lysholm score correlation coefficient r = 0.497, MOCART score correlation coefficient r = 0.579, VAS score correlation coefficient r = 0.242, T2 value correlation coefficient r=-0.293, P < 0.001). Age-stratified analysis of the patients in the microfracture combined with fibrinogen platelet-rich plasma treatment group showed that the effect of the combined treatment was more pronounced in elderly patients. Conclusions: The results of the study showed that compared with microfracture alone, microfracture combined with fibrinogen platelet-rich plasma therapy can further improve patients' knee joint-related function and their quality of life after treatment. The improvement was more obvious in elderly patients. [ABSTRACT FROM AUTHOR]

Background: Treatment of articular cartilage injury remains a challenging clinical problem in orthopedics. Chitosan-derived biomaterial could be a potential adjuvant treatment to improve cartilage repair. In the current study, we examined the effects of two potential chitosan-derived materials on cartilage regeneration of osteochondral defects in rabbits. Methods: An osteochondral defect was created over the rabbit knee and treated using three approaches: group A received no material (n = 24), group B received chitosan membranes with glucose absorption (CGA; n = 25), and group C received chitosan-glucose derivative membranes obtained via the Maillard reaction (CGMR; n = 25). Cartilage repair over the osteochondral defect was analyzed 12 weeks post-surgery via histological analysis, immunostaining, and reverse transcription-qualitative polymerase chain reaction (RT-qPCR) for type-I and type-II collagen mRNA. Results: According to histological analysis, CGMR-treated defects showed significantly improved modified O'Driscoll scoring when compared with no material- and CGA-treated defects (20.9 ± 4.3 vs. 13.00 ± 2.5 and 17.7 ± 4.6, p < 0.001). Moreover, group C exhibited higher intensity of type-II collagen immunohistochemical staining over the regenerated cartilage than groups A and B, along with increased expression of type-II collagen mRNA by RT-qPCR. Conclusions: CGMR might improve cartilage regeneration in osteochondral defects. [ABSTRACT FROM AUTHOR]

Background: With the rapid growth of the ageing population, chronic diseases such as osteoarthritis have become one of the major diseases affecting the quality of life of elderly people. The main pathological manifestation of osteoarthritis is articular cartilage damage. Alleviating and repairing damaged cartilage has always been a challenge. The application of cartilage tissue engineering methods has shown promise for articular cartilage repair. Many studies have used cartilage tissue engineering methods to repair damaged cartilage and obtained good results, but these methods still cannot be used clinically. Therefore, this study aimed to investigate the effect of incorporating nerve growth factor (NGF) into a silk fibroin (SF)/chitosan (CS) scaffold containing bone marrow-derived mesenchymal stem cells (BMSCs) on the repair of articular cartilage defects in the knees of rabbits and to explore the possible underlying mechanism involved. Materials and methods: Nerve growth factor-loaded sustained-release microspheres were prepared by a double emulsion solvent evaporation method. SF/CS scaffolds were prepared by vacuum drying and chemical crosslinking. BMSCs were isolated and cultured by density gradient centrifugation and adherent culture. NGF-SF/CS-BMSC composites were prepared and implanted into articular cartilage defects in the knees of rabbits. The repair of articular cartilage was assessed by gross observation, imaging and histological staining at different time points after surgery. The repair effect was evaluated by the International Cartilage Repair Society (ICRS) score and a modified Wakitani score. In vitro experiments were also performed to observe the effect of different concentrations of NGF on the proliferation and directional differentiation of BMSCs on the SF/CS scaffold. Results: In the repair of cartilage defects in rabbit knees, NGF-SF/CS-BMSCs resulted in higher ICRS scores and lower modified Wakitani scores. The in vitro results showed that there was no significant correlation between the proliferation of BMSCs and the addition of different concentrations of NGF. Additionally, there was no significant difference in the protein and mRNA expression of COL2a1 and ACAN between the groups after the addition of different concentrations of NGF. Conclusion: NGF-SF/CS-BMSCs improved the repair of articular cartilage defects in the knees of rabbits. This repair effect may be related to the early promotion of subchondral bone repair. [ABSTRACT FROM AUTHOR]

Background: Osteochondral injury is a common sports injury, and hyaline cartilage does not regenerate spontaneously when injured. However, there is currently no gold standard for treating osteochondral defects. Osteochondral autograft transplantation (OAT) is widely used in clinical practice and is best used to treat small osteochondral lesions in the knee that are < 2 cm2 in size. Autologous dual-tissue transplantation (ADTT) is a promising method with wider indications for osteochondral injuries; however, ADTT has not been evaluated in many studies. This study aimed to compare the radiographic and histological results of ADTT and OAT for treating osteochondral defects in a porcine model. Methods: Osteochondral defects were made in the bilateral medial condyles of the knees of 12 Dian-nan small-ear pigs. The 24 knees were divided into the ADTT group (n = 8), OAT group (n = 8), and empty control group (n = 8). At 2 and 4 months postoperatively, the knees underwent gross evaluation based on the International Cartilage Repair Society (ICRS) score, radiographic assessment based on CT findings and the magnetic resonance observation of cartilage repair tissue (MOCART) score, and histological evaluation based on the O'Driscoll histological score of the repair tissue. Results: At 2 months postoperatively, the ICRS score, CT evaluation, MOCART score, and O'Driscoll histological score were significantly better in the OAT group than the ADTT group (all P < 0.05). At 4 months postoperatively, the ICRS score, CT evaluation, MOCART score, and O'Driscoll histological score tended to be better in the OAT group than the ADTT group, but these differences did not reach statistical significance (all P > 0.05). Conclusions: In a porcine model, ADTT and OAT are both effective treatments for osteochondral defects in weight bearing areas. ADTT may be useful as an alternative procedure to OAT for treating osteochondral defects. [ABSTRACT FROM AUTHOR]

Background: Autogenous osteochondral mosaicplasty (AOM) is a widely used optimal surgical technique for cartilage repair in young patients with focal articular cartilage defects. However, the alterations in balance control in these patients after AOM have not been sufficiently investigated. This study aimed to compare different balance control performances between the patients with knee cartilage defects and healthy controls before and after AOM, as well as evaluate the influence of AOM on balance control in these patients. Methods: Static posturographic tests were performed in twenty-four patients who were scheduled for AOM two weeks pre-, three months, and one year postoperatively, along with thirty matched controls, respectively. All participants underwent posturography under four standing conditions: eyes open and closed, without and with foam support to assess the balance control ability. Subsequently, patient-reported outcome measures (PROMs) were synchronously obtained and analyzed. Results: Compared to the control subjects, less efficient balance control was observed in study patients at three testing phases (p < 0.05), whereas no alterations in postural control were visible in these patients within a year following AOM (p > 0.05). Significant improvements were found in all PROMs such as the International Knee Documentation Committee, the Lysholm Knee Score, and the visual analogue scale in the study patients postoperatively (p < 0.01). Conclusion: The results indicated that patients with knee cartilage defects have a prominent balance control deficit compared to healthy individuals. Furthermore, AOM does not improve balance control in these patients for at least one year postoperatively, and more effective approaches for postural regulation are required for the management of cartilage defect patients. [ABSTRACT FROM AUTHOR]

Background: Knee osteoarthritis (KOA) is one of the most common degenerative diseases. Its development is closely related to cartilage injury and subchondral bone remodeling homeostasis. In the present study, we combined icariin-conditioned serum (ICS) with thiolated chitosan (CSSH), a material widely used in tissue engineering for cartilage repair, to demonstrate its effect on the repair of cartilage damage and abnormal subchondral remodeling. Methods: New Zealand rabbits were undergoing surgery for cartilage defect, and joint cavity injection was performed in each group with 0.5 mL normal saline (NS), ICS, CSSH and ICS-CSSH in the right joint every week for five times. Positioning performance was observed using VICON motion capture system. Glycosaminoglycans (GAG) secretion of articular fluid was assessed. Osteoarthritis Research Society International (OARSI) score and immunohistochemical (IHC) analysis including H&E, Safranin O and collagen II staining were employed to evaluate the morphologic repair of cartilage and subchondral bone. mRNA expression of COL2A1, MMP13 and ADAMTS5 was detected in chondrocytes from injury area. Results: ICS combined with CSSH attenuated cartilage injury and abnormal subchondral remodeling in rabbits with KOA. ICS and CSSH groups showed slight improvement in positioning performance, while ICS-CSSH group exhibited better positioning performance. ICS-CSSH group showed increased GAG secretion of articular fluid and expression of COL2A1 in articular chondrocytes. Furthermore, both macroscopic observation and IHC analysis showed femoral condyle in ICS-CSSH rabbits were repaired with more native cartilage and subchondral bone regeneration. Conclusions: ICS combined with CSSH could promote the repair of osteochondral defect and stabilize subchondral bone remodeling in rabbit knees. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is a prevalent inflammatory joint disorder. microRNAs (miRNAs) are increasingly involved in OA. Aim: Our study is proposed to clarify the role of miR-124-3p in chondrocyte pyroptosis and cartilage injury in OA. Methods: OA mouse model was established via the treatment of destabilization of the medial meniscus (DMM), and the in vitro cell model was also established as mouse chondrocytes were induced by lipopolysaccharide (LPS). Mouse cartilage injury was assessed using safranin-O-fast green staining, hematoxylin–eosin staining, and OARSI grading method. Expressions of miR-124-3p, MALAT1, KLF5, and CXCL11 were determined. Cartilage injury (MMP-13, osteocalcin), inflammation (IL-6, IL-2, TNF-, IL-1β, and IL-18)- and pyroptosis-related factors (Cleaved Caspase-1 and GSDMD-N) levels were detected. Mechanically, MALAT1 subcellular localization was confirmed. The binding relationships of miR-124-3p and MALAT1 and MALAT1 and KLF5 were verified. MALAT1 half-life period was detected. Then, miR-124-3p was overexpressed using agomiR-124-3p to perform the rescue experiments with oe-MALAT1 or oe-CXCL11. Results: miR-124-3p was downregulated in DMM mice and LPS-induced chondrocytes where cartilage injury, and increased levels of inflammation- and pyroptosis-related factors were found. miR-124-3p overexpression relieved cartilage injury and repressed chondrocyte pyroptosis. miR-124-3p bounds to MALAT1 to downregulate its stability and expression, and MALAT1 bounds to KLF5 to enhance CXCL11 transcription. Overexpression of MALAT1 or CXCL11 annulled the repressive function of miR-124-3p in chondrocyte pyroptosis. Conclusion: miR-124-3p reduced MALAT1 stability and inhibited the binding of MALAT1 and KLF5 to downregulate CXCL11, thereby suppressing chondrocyte pyroptosis and cartilage injury in OA. [ABSTRACT FROM AUTHOR]

Background: The efficacy and safety profile of mesenchymal stem cells (MSCs) augmentation in chondral procedures are controversial. This systematic review updated the current evidence on MSCs augmentation for chondral procedures in patients with symptomatic chondral defects of the knee. Methods: This study followed the PRISMA guidelines. The literature search was updated in August 2022. Two independent authors accessed PubMed, Google scholar, Embase, and Scopus. No additional filters or time constrains were used for the search. A cross reference of the bibliographies was also performed. All the clinical studies investigating surgical procedures for chondral defects of the knee augmented with MSCs were accessed. Defects of both tibiofemoral and patellofemoral joints were included. The following patient reported outcomes measures (PROMs) were retrieved at baseline and last follow-up: Visual Analogic Scale (VAS), Tegner Activity Scale, Lysholm Knee Scoring System, International Knee Documentation Committee (IKDC). Return to daily activities and data on hypertrophy, failure, revision surgery were also collected. Failures were defined as the recurrence of symptoms attributable to the index procedure. Revisions were defined as any reoperation at the site of the index procedure. Results: A total of 15 clinical studies (411 procedures) were included. Patients returned to their prior sport activity at 2.8 ± 0.4 months. All the PROMs improved at last follow-up: Tegner (P = 0.0002), Lysholm (P < 0.0001), the IKDC (P < 0.0001), VAS (P < 0.0001). At a mean of 30.1 ± 13.9 months, 3.1% (2 of 65 patients) reported graft hypertrophy, 3.2% (2 of 63) were considered failures. No surgical revision procedures were reported. Given the lack of available quantitative data for inclusion, a formal comparison of surgical procedures was not conducted. Conclusion: MSCs augmentation in selected chondral procedures could be effective, with a low rate of complications. Further investigations are required to overcome the current limitations to allow the clinical translation of MSCs in regenerative medicine. [ABSTRACT FROM AUTHOR]

Background: Injuries to the articular cartilage of the knee often fail to heal properly due to the hypocellular and avascular nature of this tissue. Subsequent disability can limit participation in sports and decrease quality of life. Subchondral bone perforations are used for the treatment of small defects. Filling out the central portion in larger lesions becomes difficult, and scaffolds can be used as adjuvants, providing a matrix onto which the defect can be filled in completely. Also, autogenous cartilage grafts can be combined, acting as an inducer and improving healing quality, all in a single procedure. Methods: This observational study evaluated the clinical and quality-of-life outcomes of patients with articular cartilage lesions of the knee undergoing repair via a microfracture technique combined with a synthetic scaffold and autogenous cartilage graft, with transosseous sutures and fibrin glue fixation, at 12 months of follow-up. Secondarily, it assessed whether combined procedures, previous surgical intervention, traumatic aetiology, lesion location, and age affect outcomes. The sample consisted of adult patients (age 18–66 years) with symptoms consistent with chondral or osteochondral lesions, isolated or multiple, ICRS grade III/IV, 2–12 cm2 in size. Patients with corrected angular deviations or instabilities were included. Those with BMI > 40 kg/m2, prior total or subtotal (> 30%) meniscectomy, second-look procedures, and follow-up < 6 months were excluded. Pain (VAS), physical activity (IKDC), osteoarthritis (WOMAC), and general quality of life (SF-36) were assessed. Results: 64 procedures were included, comprising 60 patients. There was significant improvement (P < 0.05) in VAS score (5.92–2.37), IKDC score (33.44–56.33), and modified WOMAC score (53.26–75.93) after surgery. The SF-36 showed significant improvements in the physical and mental domains (30.49–40.23 and 46.43–49.84 respectively; both P < 0.05). Conclusions: Combination of microfractures, autogenous crushed cartilage graft, synthetic scaffold, and transosseous sutures with fibrin glue provides secure fixation for treatment of articular cartilage lesions of the knee. At 12-month follow-up, function had improved by 20 points on the IKDC and WOMAC, and quality of life, by 10 points on the SF-36. Age > 45 years had a negative impact on outcomes. [ABSTRACT FROM AUTHOR]

Background: Patellar dislocations in patients presenting with recurrent patellofemoral instability can damage the surrounding structures, limiting patient's participation to recreational activities and quality of life. This study evaluated frequency, location, and extent of associated injuries in patients with recurrent patellar dislocation. Methods: This systematic review was conducted according to the PRISMA checklist. PubMed, Google scholar, Embase, and Web of Science databases were accessed in July 2021. All the published clinical studies reporting frequency, location, and extent of soft tissue lesions in patients with recurrent patellar dislocations were accessed. Results: Data from 9 articles (232 patients) were retrieved. The mean age of the included patients was 21.2 ± 5.6 years. 84.8% of patients suffering from recurrent patellar dislocations demonstrated patellar chondral defects: medial facet (34.9%), while patellar crest (34.8%) and lateral facet (17%). 27.8% of patients demonstrated trochlear chondral injuries. Conclusion: Chondral defects of the medial facet and the crest of the patella are the most common in patients with recurrent patellofemoral instability. [ABSTRACT FROM AUTHOR]

Background: Talar cartilage injury is a kind of disease that causes long-term and chronic pain of ankle joint. Autologous osteochondral transplantation has been viewed as an alternative choice for treating these lesions, but donor-site morbidity has limited its application. This study aimed to analyze the efficacy of iliac bone autografting for Hepple V osteochondral lesions of the talus. Methods: This retrospective study included 32 patients surgically treated for Hepple V osteochondral lesions of the talus from January 2015 to January 2020. All patients underwent open surgery. Ipsilateral iliac bone grafts were taken and filled with talar cartilage injury area. The improvement of postoperative ankle pain was evaluated by Visual Analogue Scale (VAS), and the improvement of ankle function was evaluated by the American Orthopaedic Foot & Ankle Society (AOFAS). During the postoperative follow-up, X-ray examination of the front and side of the ankle joint and CT of the ankle joint were performed to evaluate the bone cartilage healing in the graft area. Results: Thirty-two patients (32 ankles) (100%) returned for clinical and radiologic follow-up at an average of 28 (range 24–36) months postoperatively. At 3 months postoperatively and at the last follow-up, the AOFAS scores were (80.4 ± 3.6) and (89.2 ± 6.4), respectively, which were significantly improved compared with the preoperative score (49.7 ± 8.1), and the difference was statistically significant (P < 0.05). The VAS scores were (2.1 ± 0.9) and (1.5 ± 0.8), respectively, which were significantly better than the preoperative score (6.2 ± 1.7), and the difference was statistically significant (P < 0.05). Re-examination of the front and side of the ankle joint X-rays and CT showed that the bone healing at the osteotomy of medial malleolus and osteochondral transplantation area. All patients had no pain at the donor site. No complications occurred in 32 patients at the last follow-up. Conclusions: With iliac bone autografting for Hepple V osteochondral lesions of the talus can effectively relieve ankle joint pain and significantly improved ankle function. Level of evidence: Level III, Retrospective series. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is characterized by joint pain and joint function limitation. Hsa_circ_0045714 (circ_0045714) is a novel OA-related circular RNA. However, its repertoire remains to be further clarified in joint chondrocytes. Methods: RNA and protein expression levels and inflammatory factor levels were detected by real-time quantitative polymerase chain reaction, western blotting and enzyme-linked immunosorbent assay. Cell proliferation and apoptosis were determined by colony formation assay, cell counting kit-8 assay and apoptosis assay. Direct interaction was predicted by bioinformatics method and confirmed by dual-luciferase reporter assay. Results: Expression of circ_0045714 and phosphoinositide-3-kinase (PI3K) regulatory subunit 3 (PIK3R3) was declined, and microRNA (miR)-331-3p was promoted in knee articular cartilages and cells from OA patients, as well as interleukin (IL)-1β-challenged human articular chondrocytes (HAC) cell line. In stimulation of IL-1β, HAC cells showed a loss of colony formation ability, cell viability and expression of Bcl-2 and Collagen II, allied with an increase in apoptosis rate and levels of IL-6, IL-8 and tumor necrosis factor-α, Bcl-2-associated X protein, cleaved caspase-3, and ADAM with thrombospondin motif-5. Noticeably, overexpressing circ_0045714 and inhibiting miR-331-3p could suppress IL-1β-evoked these effects, and both were through up-regulating PIK3R3, a key gene in PI3K/AKT signaling pathway. Mechanically, circ_0045714 functioned as competing endogenous RNA (ceRNA) for miR-331-3p and further regulated expression of the downstream target gene PIK3R3. Conclusion: There was a novel circ_0045714/miR-331-3p/PIK3R3 ceRNA axis in HAC, and its inhibition might be one mechanism of HAC injury in OA. [ABSTRACT FROM AUTHOR]

Background: Focal chondral defects of the knee are common. Several surgical techniques have been proposed for the management of chondral defects: microfractures (MFX), osteochondral autograft transplantation (OAT), autologous matrix-induced chondrogenesis (AMIC) and autologous chondrocyte implantation (ACI)—first generation (pACI), second generation (cACI) and third generation (mACI). A Bayesian network meta-analysis was conducted to compare these surgical strategies for chondral defects in knee at midterm follow-up. Methods: This Bayesian network meta-analysis was conducted according to the PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions. PubMed, Google Scholar, Embase and Scopus databases were accessed in July 2021. All the prospective comparative clinical trials investigating two or more surgical interventions for chondral defects of the knee were accessed. The network meta-analyses were performed through a Bayesian hierarchical random-effects model analysis. The log odds ratio (LOR) effect measures were used for dichotomic variables, while the standardized mean difference (SMD) for the continuous variables. Results: Data from 2220 procedures (36 articles) were retrieved. The median follow-up was 36 (24 to 60) months. The ANOVA test found good baseline comparability between symptoms duration, age, sex and body mass index. AMIC resulted in higher Lysholm score (SMD 3.97) and Tegner score (SMD 2.10). AMIC demonstrated the lowest rate of failures (LOR −0.22) and the lowest rate of revisions (LOR 0.89). As expected, MFX reported the lower rate of hypertrophy (LOR −0.17) followed by AMIC (LOR 0.21). No statistically significant inconsistency was found in the comparisons. Conclusion: AMIC procedure for focal chondral defects of the knee performed better overall at approximately 3 years' follow-up. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to analyse the re-operation rate after surgical treatment of osteochondral lesions of the talus (OCLTs) in children and adolescents. Methods: Between 2009 and 2019, 27 consecutive patients with a solitary OCLT (10 male, 17 female; mean age 16.9 ± 2.2 years; 8 idiopathic vs. 19 traumatic) received primary operative treatment (arthroscopy + bone marrow stimulation [BMS], n = 8; arthroscopy + retrograde drilling, n = 8; autologous chondrocyte implantation [ACI]/autologous bone grafting, n = 9; arthroscopy + BMS + retrograde drilling; n = 1; flake fixation, n = 1). Seventeen OCLTs were located at the medial and ten at the lateral talus. 'Re-operation' as the outcome measure was evaluated after a median follow-up of 42 months (range 6–117 months). Patients were further subdivided into groups A (re-operation, n = 7) and B (no re-operation, n = 20). Groups A and B were compared with respect to epidemiological, lesion- and therapy-related variables. Results: Seven of 27 patients needed a re-operation (re-operation rate 25.9% after a median interval of 31 months [range 13–61 months]). The following operative techniques were initially used in these seven patients: arthroscopy + BMS n = 2, arthroscopy + retrograde drilling n = 4, ACI + autologous bone grafting n = 1. A comparison of group A with group B revealed different OCLT characteristics between both groups. The intraoperative findings according to the International Cartilage Repair Society (ICRS) classification revealed significantly more advanced cartilage damage in group B than in group A (p = 0.001). Conclusions: We detected a re-operation rate of 25.9% after primary surgical OCLT treatment. Patients with re-operation had significantly lower ICRS classification stages compared to patients without re-operation. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the clinical efficacy of arthroscopic therapy with infrapatellar fat pad cell concentrates in treating knee cartilage lesions, we conducted a prospective randomized single-blind clinical study of controlled method. Methods: Sixty cases from Shanghai Changzheng Hospital from April 2018 to December 2019 were chosen and randomly divided into 2 groups equally. Patients in the experiment group were treated through knee arthroscopy with knee infrapatellar fat pad cell concentrates containing mesenchymal stromal cells, while patients in the control group were treated through regular knee arthroscopic therapy. VAS and WOMAC scores were assessed at pre-operation, and 6 weeks, 12 weeks, 6 months, and 12 months after intervention. MORCART scores were assessed at pre-operation and 12 months after intervention. Results: Twenty-nine cases in the experiment group and 28 cases in the control group were followed up. No significant difference in VAS, WOMAC, and MOCART scores were found between the two groups before surgery (P > 0.05). The WOMAC total and WOMAC function scores of the experiment group were significantly lower than those of the control group 6 months and 12 months after surgery (P < 0.05). The VAS rest and VAS motion scores of the experiment group were found significantly lower than those of the control group 12 months after surgery (P < 0.05). The MOCART scores of the experiment group were found significantly higher compared with the control group 12 months after surgery (P < 0.05). No significant difference in WOMAC stiffness scores were found between the two groups. Conclusions: The short-term results of our study are encouraging and demonstrate that knee arthroscopy with infrapatellar fat pad cell concentrates containing mesenchymal stromal cells is safe and provides assistance in reducing pain and improving function in patients with knee cartilage lesions. Trial registration: ChiCTR1800015379. Registered on 27 March 2018, http://www.chictr.org.cn/showproj.aspx?proj=25901. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the repairing effects of glucosamine sulfate combined with etoricoxib on articular cartilages of patients with knee osteoarthritis (KOA). Methods: A total of 106 KOA patients were randomly divided into control (n = 40) and experimental groups (n = 66) and treated with etoricoxib alone and glucosamine sulfate plus etoricoxib, respectively. Changes in WOMAC score and clinical efficacy were observed. The synovial fluid was extracted. Bone metabolism indices, growth factors, inflammatory factors, matrix metalloproteinases (MMPs), and NO-induced apoptosis-related factors were measured by ELISA. JNK and Wnt5a mRNA levels were determined using RT-PCR. Results: After treatment, the total WOMAC scores of both groups significantly declined (P < 0.05), being lower in experimental group. The total effective rate of experimental group was higher (P < 0.05). BGP and OPG levels rose, especially in experimental group (P < 0.05). CTX-II, COMP, and RANKL levels decreased, particularly in experimental group (P < 0.05). TGF-β, IGF-1, and FGF-2 levels increased, especially in experimental group (P < 0.05). Both groups, particularly experimental group, had decreased levels of IL-1β, IL-17, IL-18, TNF-α, MMP-3, MMP-9, and MMP-13 (P < 0.05). JNK and Wnt5a mRNA levels of both groups dropped, which were lower in experimental group (P < 0.05). NO and LPO levels reduced, being lower in experimental group. SOD level rose, especially in experimental group (P < 0.05). Conclusion: Glucosamine sulfate plus etoricoxib can repair the articular cartilages of KOA patients. Probably, JNK and Wnt5a are downregulated to inhibit the secretion of MMPs through lowering the levels of inflammatory factors, thereby delaying cartilage matrix degradation. NO-induced chondrocyte apoptosis may be suppressed via the SOD pathway. [ABSTRACT FROM AUTHOR]

Background: Anterior cruciate ligament (ACL) revision surgery has been associated with inferior outcome compared with primary ACL reconstruction. However, this has rarely been investigated in a consecutive cohort limited to patients that have undergone both primary and revision ACL reconstruction. This study aimed to assess differences in outcome and concomitant injuries between primary and revision ACL reconstruction in such a cohort, and to identify predictors of the patient-reported outcome after ACL revision. Methods: Patients who had undergone both primary and revision ACL reconstruction were identified in the Swedish National Knee Ligament Registry. Patients aged 13–49 years with hamstring tendon primary ACL reconstruction and data on the Knee Injury and Osteoarthritis Outcome Score (KOOS) on at least one occasion (preoperative or one year postoperatively) at both surgeries were eligible. Concomitant injuries and the KOOS were compared between each patient's primary and revision ACL reconstruction. Linear regression analyses were performed to determine predictors of the one-year KOOS after ACL revision. Results: A total of 1014 patients were included. Cartilage injuries increased at ACL revision (p < 0.001), as 23.0% had a cartilage injury at ACL revision that was not present at primary ACL reconstruction. The 1-year KOOS was lower after ACL revision compared with primary ACL reconstruction, with the largest difference in the KOOS sports and recreation (5.2 points, SD 32.2, p = 0.002). A posterolateral corner (PLC) injury at ACL revision was a negative predictor of KOOS, with the largest effect on the sports and recreation subscale (β = − 29.20 [95% CI − 50.71; − 6.69], p = 0.011). The use of allograft for ACL revision was an independent predictor of a poorer KOOS QoL (β = − 12.69 [95% CI − 21.84; − 3.55], p = 0.0066) and KOOS4 (β = − 11.40 [95% CI − 19.24; − 3.57], p = 0.0044). Conclusion: Patients undergoing ACL revision reported a 1-year outcome that was slightly inferior to the 1-year outcome after their primary ACL reconstruction. An ACL revision was associated with an increase in cartilage injuries. A PLC injury at ACL revision and the use of allograft for ACL revision predicted a clinically relevant poorer KOOS one year after ACL revision. [ABSTRACT FROM AUTHOR]

Background: It is difficult to repair cartilage damage when cartilage undergoes trauma or degeneration. Cartilage tissue engineering is an ideal treatment method to repair cartilage defects, but at present, there are still some uncertainties to be researched in cartilage tissue engineering including the mechanical properties of the repaired region. Methods: In this study, using an agarose gel as artificial cartilage implanted into the cartilage defect and gluing the agarose gel to cartilage by using the medical bio-adhesive, the full-thickness and half-thickness defects models of articular cartilage in vitro repaired by tissue engineering were constructed. Strain behaviors of the repaired region were analyzed by the digital correlation technology under 5,10, 15, and 20% compressive load. Results: The axial normal strain (Ex) perpendicular to the surface of the cartilage and lateral normal strain (Ey) as well as shear strain (Exy) appeared obviously heterogeneous in the repaired region. In the full-defect model, Ex showed depth- dependent strain profiles where maximum Ex occurs at the low middle zone while in the half-defect mode, Ex showed heterogeneous strain profiles where maximum Ex occurs at the near deep zone. Ey and Exy at the interface site of both models present significantly differed from the host cartilage site. Ey and Exy exhibited region-specific change at the host, interface, and artificial cartilage sites in the superficial, middle, and deep zones due to the artificial cartilage implantation. Conclusion: Both defect models of cartilage exhibited a heterogeneous strain field due to the engineered cartilage tissue implant. The abnormal strain field can cause the cells within the repaired area to enter complex mechanical states which will affect the restoration of cartilage defects. [ABSTRACT FROM AUTHOR]

Background: Although differences in the results of the bone marrow stimulation technique between the knee and ankle have been reported, a detailed mechanism for those differences has not been clarified. The purpose of this study was to examine whether morphological differences between the knee and ankle joint affect the results of drilling as treatment for osteochondral defects in a rabbit model. Methods: Osteochondral defects were created at the knee and ankle joint in the rabbit. In the knee, osteochondral defects were created at the medial femoral condyle (MFC) and patellar groove (PG). At the ankle, defects were created in the talus at either a covered or uncovered area by the tibial plafond. After creating the osteochondral defect, drilling was performed. At 4, 8, and 12 weeks after surgery, repair of the osteochondral defects were evaluated histologically. The proliferation of rabbit chondrocytes and proteoglycan release of cartilage tissue in response to IL- 1β were analyzed in vitro in both joints. Results: At 8 weeks after surgery, hyaline cartilage repair was observed in defects at the covered area of the talus and the MFC. At 12 weeks, hyaline cartilage with a normal thickness was observed for the defect at the covered area of the talus, but not for the defect at the MFC. At 12 weeks, subchondral bone formation progressed and a normal contour of subchondral bone was observed on CT in the defect at the covered area of the talus. No significant differences in chondrocyte proliferation rate and proteoglycan release were detected between the knee and ankle in vitro. Conclusions: Our results demonstrate that the covered areas of the talus show early and sufficient osteochondral repair compared to that of the knee and the uncovered areas of the talus. These results suggest that the congruent joint shows better subchondral repair prior to cartilage repair compared to that of the incongruent joint. [ABSTRACT FROM AUTHOR]

Background: The purpose was to determine the influence of irrigation solution osmolarity on articular chondrocytes survival and metabolic state following mechanical injury. Methods: Osteochondral explants were harvested from patients undergoing total knee arthroplasty for osteoarthritis and then cut through their full thickness to establish mechanical injury models. Cartilage explants were incubated in irrigation solutions (saline and balanced salt) with different osmolarities (180, 280, 380, 580 mOsm/L) for 2 h. The percentage of cell death (100 × number of dead cells/number of dead and live cells) was quantified with the laser confocal microscopy. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was performed to detect apoptosis index of injured cartilage. The contents of proteoglycan elution were determined by spectrophotometer at 530 nm, and HIF-1α and type II collagen mRNA yields were quantified with real-time PCR. Results: In situ dead chondrocytes were mainly localized to the superficial tangential region of injured cartilage edge after mechanical injury. The percentage of cell death was decreased, and proteoglycan elution was gradually reduced with the increasing of osmolarity. The apoptosis indices of TUNEL assay in different osmolarities had no significant difference (P = 0.158). HIF-1α and type II collagen mRNA yields were the least for chondrocytes exposed to 180 mOsm/L medium and were the greatest for chondrocytes exposed to 380 mOsm/L medium. Compared with the saline group, the cell death of superficial zone was significantly decreased (P = 0.001) and contents of proteoglycan elution were also significantly decreased (P = 0.045) in the balanced salt. HIF-1α (P = 0.017) and type II collagen (P = 0.034) mRNA yields in the chondrocytes exposed to the balanced salt were significantly more than the saline group. Conclusion: The osmolarity of irrigation solutions plays an important role in the survival and metabolic state of chondrocytes following mechanical injury, and the chondrocyte death is not caused by apoptosis. Increasing osmolarity of irrigation solutions may be chondroprotective with decreasing the chondrocyte death, reducing inhibition of metabolism and proteoglycan elution, ultimately preventing cartilage degeneration and promoting integrative repair. [ABSTRACT FROM AUTHOR]

Background: Full-thickness articular cartilage injury of the knee is a major cause of disability. The aim of this study is to assess the outcome of patients treated with differentiated to chondrocytes bone marrow mesenchymal stem cells (BM-MSCs) cultured on a collagen type I/III (Chondro-Gide®) scaffold. The secondary aim was to confirm the absence of adverse events. Methods: Fifteen patients (19 knees) with symptomatic full-thickness cartilage defects of the knee were enrolled. Bone marrow was harvested from the iliac crest, BM-MSCs were prepared, and expanded cells were grown in a standard medium or in a standard culture medium containing TGF-β. BM-MSCs differentiated to chondrocytes were seeded in a porcine collagen type I/III scaffold (Chondro-Gide®) and cultured in TGF-β containing media. After 4 weeks, the membrane was sutured on the cartilage defect. All patients underwent plain radiographs (antero-posterior, lateral, and axial view of the patella) and MRI of the affected knee. The Oxford knee score, the Lyhsolm scale, and the VAS score were administered to all patients. At final follow-up a MRI for the study of articular cartilage was undertaken. Results: The mean size of the cartilage lesions was 20 × 17 mm (range, 15 × 10 mm–30 × 30 mm). At final follow-up, the median Oxford knee score and Lyhsolm scale scores significantly improved from 29 (range 12–39; SD 7.39) to 45 (range 24–48; SD 5.6) and from 55.5 (range 25–81; SD 17.7) to 94.5 (58–100; SD 10.8), respectively. Pain, according to the VAS score, significantly improved. Sixty percent of patients reported their satisfaction as excellent, 20% as good, 14% as fair, and 1 patient as poor. Conclusion: The treatment of full-thickness chondral injuries of the knee with differentiated to chondrocytes BM-MSCs and Chondro-Gide® scaffold showed encouraging outcomes. Further studies involving more patients, and with longer follow-up, are required to evaluate the effectiveness of the treatment and the long-term results. [ABSTRACT FROM AUTHOR]

This article [2] was published twice [1] due to a production error. The original article [1] should be considered the version of record and used for citation purposes. The publisher apologizes to the authors and readers for the error and any inconvenience caused. [ABSTRACT FROM AUTHOR]

Background: Chondral injury is a common problem around the world. Currently, there are several treatment strategies for these types of injuries. The possible complications and problems associated with conventional techniques lead us to investigate a minimally invasive and biotechnological alternative treatment. Combining tissue-engineering and microencapsulation technologies provide new direction for the development of biotechnological solutions. The aim of this study is to develop a minimal invasive tissue-engineering approach, using bio-targeted microspheres including autologous cells, for the treatment of the cartilage lesions. Method: In this study, a total of 28 sheeps of Akkaraman breed were randomly assigned to one of the following groups: control (group 1), microfracture (group 2), scaffold (group 3), and microsphere (group 4). Microspheres and scaffold group animals underwent adipose tissue collection prior to the treatment surgery. Mesenchymal cells collected from adipose tissue were differentiated into chondrocytes and encapsulated with scaffolds and microspheres. Osteochondral damage was conducted in the right knee joint of the sheep to create an animal model and all animals treated according to study groups. Results: Both macroscopic and radiologic examination showed that groups 3 and 4 have resulted better compared to the control and microfracture groups. Moreover, histologic assessments indicate hyaline-like cartilage formations in groups 3 and 4. Conclusion: In conclusion, we believe that the bio-targeted microspheres can be a more effective, easier, and safer approach for cartilage tissue engineering compared to previous alternatives. [ABSTRACT FROM AUTHOR]

Background: Biologic treatment options for cartilage injuries require chondrocyte expansion using cell culture. Clinical application is accomplished in two surgical sessions and is expensive. If isolation of chondrocytes and stimulus for proliferation and extracellular matrix synthesis can be achieved in vivo, the treatment can be performed in one session and the cost can be reduced. Methods: A 2.5-cm diameter full-thickness chondral defect was created in the knees of five groups of sheep. In one group, some of the chondral tissues obtained from the creation of the defect were diced into small pieces and were placed into the defect and were covered with a collagen membrane (MIV group). In the other group, the collagen membrane was soaked in collagenase prior to usage. In the next group, the collagen membrane was soaked in both collagenase and growth factors. Matrix-induced autologous chondrocyte implantation (MACI) was applied to another group in two sessions, and the last group was left untreated. After 15 weeks of follow-up, repair tissues were compared macroscopically, histomorphometrically, and biochemically for tissue concentrations of glycosaminoglycan and type II collagen. Results: MACI and MIV groups demonstrated better healing than others and were similar. Addition of collagenase or growth factors did not improve the results. Addition of collagenase did not have detrimental effect on the surrounding cartilage. Conclusions: With the described method, it is possible to obtain comparable results with MACI. Further studies are also needed to see if it works similarly in humans. [ABSTRACT FROM AUTHOR]