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Chondral defects in the athlete's hip are a relatively common occurrence, often presenting with debilitating pain and activity limitation. Preoperative identification of cartilage defects is challenging and there are many different modalities for treatment. Nonsurgical interventions, including activity modification, physical therapy, and injections, play a vital role, especially in less severe cases and as adjuncts to surgical intervention. Treating surgeons must be familiar with the cartilage restoration procedures available, including debridement, microfracture, and various implantation and transplantation options. Safe and effective management of cartilage defects is imperative to an athlete's return to sport. It is also imperative that surgeons are aware of all these various treatment options to determine what modality is best for their patients. This review serves to outline these options, cover the published literature, and provide general guidelines for surgeons when they encounter chondral defects in the office and the operating room. [ABSTRACT FROM AUTHOR]

Background: Chondral defects in the knee present a significant challenge due to their limited self-healing capacity, often leading to joint degeneration and functional disability. Current treatments, including surgical approaches like mosaicplasty and regenerative therapies such as bone marrow aspirate concentrate (BMAC) augmentation, aim to address these defects and improve patient outcomes. Materials and Methods: This study conducted a single-center, randomized controlled trial to evaluate the efficacy of different treatment approaches and rehabilitation protocols for chondral defects. Thirty-seven subjects presenting with symptomatic chondral or osteochondral defects (>3 cm2) in the weight-bearing region of the femoral condyle were partitioned into three groups, and underwent mosaicplasty with or without BMAC augmentation, followed by either a 6-week or 12-week rehabilitation program. Group 1 (n = 10) received mosaicplasty combined with BMAC augmentation and engaged in a twelve-week two-phase rehabilitation protocol. Group 2 (n = 15) underwent mosaicplasty alone and participated in the same twelve-week two-phase rehabilitation regimen. Meanwhile, Group 3 (n = 12) underwent mosaicplasty and underwent a shorter six-week one-phase rehabilitation program. Clinical assessments were performed using the visual analog scale (VAS) for pain, goniometry for the knee's range of motion (ROM), manual muscle testing (MMT) for quadricep strength, and the Western Ontario and McMaster University Arthritis Index (WOMAC) for functional evaluation in three test phases. Results: Significant differences in WOMAC scale scores were observed between the three groups at the intermediate (F(2, 34) = 5.24, p < 0.010) and final (F(2, 34) = 111, p < 0.000) stages, with post hoc Tukey tests revealing variations shared among all three groups. The between-group analysis of the VAS scale demonstrated no statistically significant difference initially (F(2, 34) = 0.18, p < 0.982), but significant differences emerged following the intermediate (F(2, 34) = 11.40, p < 0.000) and final assessments (F(2, 34) = 59.87, p < 0.000), with post hoc Tukey tests revealing specific group variations, notably between Group 1 and both Group 2 and Group 3, and also between Group 3 and Group 2. The between-group analysis of quadricep muscle strength using MMT scores revealed no statistically significant differences initially (F(2, 34) = 0.376, p < 0.689) or following the intermediate assessment (F(2, 34) = 2.090, p < 0.139). The one-way ANOVA analysis showed no significant difference in the knee ROM initially (F(2, 34) = 1.037, p < 0.366), but significant differences emerged following intermediate (F(2, 34) = 9.38, p < 0.001) and final assessments (F(2, 34) = 11.60, p < 0.000). Post hoc Tukey tests revealed significant differences between Groups 1 and 2, Groups 1 and 3, and Groups 2 and 3 at intermediate and final assessments. Conclusions: The patients who received BMAC augmentation and completed a 12-week rehabilitation protocol had significantly better outcomes in pain relief, knee function, and ROM when compared to those who did not receive BMAC augmentation or those who completed a shorter rehabilitation period. Our findings suggest that combining mosaicplasty with BMAC augmentation and a comprehensive rehabilitation program can lead to superior clinical outcomes for patients with chondral defects in the knee. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate clinical and instrumental outcomes of the autologous matrix-induced chondrogenesis (AMIC) technique for the treatment of isolated traumatic condyle and femoropatellar cartilage lesions. A total of 25 patients (12 males, 13 females, mean age 47.3 years) treated between 2018 and 2021 were retrospectively reviewed and subdivided into two groups based on age (Group A, age < 45 years; Group B, age > 45 years). A clinical evaluation was performed using the International Knee Documentation Committee (IKDC), Lysholm score and Visual Analogue Score (VAS). Cartilage regeneration was evaluated via magnetic resonance (1.5 Tesla) and classified according to a Magnetic resonance Observation of CArtilage Repair Tissue (MOCART) scoring system. At a minimum follow-up of 2 years, Group A patients obtained greater instrumental results in comparison to group B: in fact, the MOCART score was statistically significantly correlated with IKDC (r = 0.223) (p < 0.001) exclusively in group A. Nevertheless, a significant improvement in clinical functionality was shown in Group B (p < 0.001), demonstrating that this technique is safe, reproducible and capable of offering satisfactory clinical results regardless of age. [ABSTRACT FROM AUTHOR]

Background: Chondral defects in the knee present a significant challenge due to their limited self-healing capacity, often leading to joint degeneration and functional disability. Current treatments, including surgical approaches like mosaicplasty and regenerative therapies such as bone marrow aspirate concentrate (BMAC) augmentation, aim to address these defects and improve patient outcomes. Materials and Methods: This study conducted a single-center, randomized controlled trial to evaluate the efficacy of different treatment approaches and rehabilitation protocols for chondral defects. Thirty-seven subjects presenting with symptomatic chondral or osteochondral defects (>3 cm2) in the weight-bearing region of the femoral condyle were partitioned into three groups, and underwent mosaicplasty with or without BMAC augmentation, followed by either a 6-week or 12-week rehabilitation program. Group 1 (n = 10) received mosaicplasty combined with BMAC augmentation and engaged in a twelve-week two-phase rehabilitation protocol. Group 2 (n = 15) underwent mosaicplasty alone and participated in the same twelve-week two-phase rehabilitation regimen. Meanwhile, Group 3 (n = 12) underwent mosaicplasty and underwent a shorter six-week one-phase rehabilitation program. Clinical assessments were performed using the visual analog scale (VAS) for pain, goniometry for the knee’s range of motion (ROM), manual muscle testing (MMT) for quadricep strength, and the Western Ontario and McMaster University Arthritis Index (WOMAC) for functional evaluation in three test phases. Results: Significant differences in WOMAC scale scores were observed between the three groups at the intermediate (F(2, 34) = 5.24, p < 0.010) and final (F(2, 34) = 111, p < 0.000) stages, with post hoc Tukey tests revealing variations shared among all three groups. The between-group analysis of the VAS scale demonstrated no statistically significant difference initially (F(2, 34) = 0.18, p < 0.982), but significant differences emerged following the intermediate (F(2, 34) = 11.40, p < 0.000) and final assessments (F(2, 34) = 59.87, p < 0.000), with post hoc Tukey tests revealing specific group variations, notably between Group 1 and both Group 2 and Group 3, and also between Group 3 and Group 2. The between-group analysis of quadricep muscle strength using MMT scores revealed no statistically significant differences initially (F(2, 34) = 0.376, p < 0.689) or following the intermediate assessment (F(2, 34) = 2.090, p < 0.139). The one-way ANOVA analysis showed no significant difference in the knee ROM initially (F(2, 34) = 1.037, p < 0.366), but significant differences emerged following intermediate (F(2, 34) = 9.38, p < 0.001) and final assessments (F(2, 34) = 11.60, p < 0.000). Post hoc Tukey tests revealed significant differences between Groups 1 and 2, Groups 1 and 3, and Groups 2 and 3 at intermediate and final assessments. Conclusions: The patients who received BMAC augmentation and completed a 12-week rehabilitation protocol had significantly better outcomes in pain relief, knee function, and ROM when compared to those who did not receive BMAC augmentation or those who completed a shorter rehabilitation period. Our findings suggest that combining mosaicplasty with BMAC augmentation and a comprehensive rehabilitation program can lead to superior clinical outcomes for patients with chondral defects in the knee.

Articular cartilage injuries are found in up to 60% of patients who undergo an arthroscopic knee procedure, and those that totally affect articular cartilage (grade IV) have limited regenerative capacity and extended time for recovery. 3-D scaffolds represent a novel solution to address this type of injury. Our purpose was to analyze the MRI findings and functional status of patients that underwent repair of chondral defects either by microfractures or Hyaluronan (HA) 3-D scaffolding. We conducted a retrospective study of patients with chondral defects. The outcomes analyzed in this study included anatomical changes evaluated by the Henderson score (based on MRI findings) at baseline, 6, and 12 months after surgery, and improvement in functionality evaluated by the Modified Cincinnati Knee Rating System (MCKRS) at baseline and 6 months after surgery. Clinical and demographic characteristics were similar for both groups. There was a statistically significant improvement in Henderson score for the 3-D scaffold-treated group at 6 months versus the microfracture group (p < 0.0001). Improvement in functionality, measured by the MCKRS, was more frequently found in the 3-D scaffold-treated group. In conclusion, the use of HA 3-D scaffolding was superior, with faster recovery evident 6 months after the surgery that progressed to full recovery in all patients a year after surgery. Future studies with a randomized design might help to support our findings. This study provides level III evidence. [ABSTRACT FROM AUTHOR]

The treatment of chondral and osteochondral defects is challenging. These types of lesions are painful and progress to osteoarthritis over time. Tissue engineering offers tools to address this unmet medical need. The use of an autologous cartilage construct consisting of hyaline cartilage chips embedded in plasma rich in growth factors (PRGF) has been proposed as a therapeutic alternative. The purpose of this study was to dig into the potential mechanisms behind the in vitro remodelling process that might explain the clinical success of this technique and facilitate its optimisation. Chondrocyte viability and cellular behaviour over eight weeks of in vitro culture, type II collagen synthesis, the dual delivery of growth factors by hyaline cartilage and PRGF matrix, and the ultrastructure of the construct and its remodelling were characterised. The main finding of this research is that the cartilage fragments embedded in the three-dimensional PRGF scaffold contain viable chondrocytes that are able to migrate into the fibrin network, proliferate and synthesise extracellular matrix after the second week of in vitro culture. The characterization of this three-dimensional matrix is key to unravelling the molecular kinetics responsible for its efficacy. [ABSTRACT FROM AUTHOR]

Abstract Background The management of chondral defects of the patellofemoral joint is debated, and definitive evidence is lacking. This study systematically updated and summarised the current literature on the surgical management of isolated chondral defects of the patellofemoral joint, discussing techniques, outcome, pitfalls, and new frontiers. Methods This systematic review was conducted according to the 2020 PRISMA statement. In August 2022, PubMed, Web of Science, Google Scholar, and Embase databases were accessed with no time constrain. All the clinical studies investigating the surgical management of chondral defects of the patellofemoral joint were retrieved. Articles which reported data on patients with advanced to severe osteoarthritis were not eligible. Only studies with a minimum 24 months follow-up were considered. Studies which mixed results of patellofemoral and tibiofemoral joints were not considered. Results Data from 10 studies (692 procedures) were retrieved. The mean follow-up was 46.9 ± 18.2 months. The mean age of the patients was 34.0 ± 6.1 years, and the mean BMI was 25.9 ± 0.8 kg/m2. The mean duration of symptoms before the index surgery was 81.0 ± 24.0 months. The mean defect size was 3.8 ± 0.8 cm2. All the PROMs improved from baseline to last follow-up: VAS 0–10 (P = 0.04), Tegner (P = 0.02), Lysholm (P = 0.03), and International Knee Documentation Committee (P = 0.03). The rate of hypertrophy was 5.6% (14 of 251), the rate of progression to total knee arthroplasty was 2.4% (2 of 83), the rate of revision was 16.9% (29 of 136), and the rate of failure was 13.0% (16 of 123). Conclusion Current surgical strategies may be effective to improve symptoms deriving from chondral defects of the patellofemoral joint. The limited and heterogeneous data included for analysis impact negatively the results of the present study. Further clinical studies are strongly required to define surgical indications and outcomes, and the most suitable technique.

Abstract 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

Introduction: Cartilage defects in the knee can be caused by injury, various types of arthritis, or degeneration. As a long-term consequence of cartilage defects, osteoarthritis can develop over time, often leading to the need for a total knee replacement (TKR). The treatment alternatives of chondral defects include, among others, microfracture, and matrix-associated autologous chondrocyte implantation (M-ACI). The purpose of this study was to determine cost-effectiveness of M-ACI in Germany with available mid- and long-term outcome data, with special focus on the avoidance of TKR. Materials and methods: We developed a discrete-event simulation (DES) that follows up individuals with cartilage defects of the knee over their lifetimes. The DES was conducted with a status-quo scenario in which M-ACI is available and a comparison scenario with no M-ACI available. The model included 10,000 patients with articular cartilage defects. We assumed Weibull distributions for short- and long-term effects for implant failures. Model outcomes were costs, number of TKRs, and quality-adjusted life years (QALYs). All analyses were performed from the perspective of the German statutory health insurance. Results: The majority of patients was under 45 years old, with defect sizes between 2 and 7 cm2 (mean: 4.5 cm2); average modeled lifetime was 48 years. In the scenario without M-ACI, 26.4% of patients required a TKR over their lifetime. In the M-ACI scenario, this was the case in only 5.5% of cases. Thus, in the modeled cohort of 10,000 patients, 2700 TKRs, including revisions, could be avoided. Patients treated with M-ACI experienced improved quality of life (22.53 vs. 21.21 QALYs) at higher treatment-related costs (18,589 vs. 14,134 € /patient) compared to those treated without M-ACI, yielding an incremental cost‐effectiveness ratio (ICER) of 3376 € /QALY. Conclusion: M-ACI is projected to be a highly cost‐effective treatment for chondral defects of the knee in the German healthcare setting. [ABSTRACT FROM AUTHOR]

A healthy articular cartilage is paramount to joint function. Cartilage defects, whether acute or chronic, are a significant source of morbidity. This review summarizes various imaging modalities used for cartilage assessment. While radiographs are insensitive, they are still widely used to indirectly assess cartilage. Ultrasound has shown promise in the detection of cartilage defects, but its efficacy is limited in many joints due to inadequate visualization. CT arthrography has the potential to assess internal derangements of joints along with cartilage, especially in patients with contraindications to MRI. MRI remains the favored imaging modality to assess cartilage. The conventional imaging techniques are able to assess cartilage abnormalities when cartilage is already damaged. The newer imaging techniques are thus targeted at detecting biochemical and structural changes in cartilage before an actual visible irreversible loss. These include, but are not limited to, T2 and T2* mapping, dGEMRI, T1ρ imaging, gagCEST imaging, sodium MRI and integrated PET with MRI. A brief discussion of the advances in the surgical management of cartilage defects and post-operative imaging assessment is also included. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate clinical and instrumental outcomes of the autologous matrix-induced chondrogenesis (AMIC) technique for the treatment of isolated traumatic condyle and femoropatellar cartilage lesions. A total of 25 patients (12 males, 13 females, mean age 47.3 years) treated between 2018 and 2021 were retrospectively reviewed and subdivided into two groups based on age (Group A, age < 45 years; Group B, age > 45 years). A clinical evaluation was performed using the International Knee Documentation Committee (IKDC), Lysholm score and Visual Analogue Score (VAS). Cartilage regeneration was evaluated via magnetic resonance (1.5 Tesla) and classified according to a Magnetic resonance Observation of CArtilage Repair Tissue (MOCART) scoring system. At a minimum follow-up of 2 years, Group A patients obtained greater instrumental results in comparison to group B: in fact, the MOCART score was statistically significantly correlated with IKDC (r = 0.223) (p < 0.001) exclusively in group A. Nevertheless, a significant improvement in clinical functionality was shown in Group B (p < 0.001), demonstrating that this technique is safe, reproducible and capable of offering satisfactory clinical results regardless of age.

Abstract Background Some authors secured the membrane during matrix-induced autologous chondrocyte implantation (mACI) with fibrin glue or did not use a formal fixation. The real impact of fibrin glue addition on chondrocytes migration and proliferation has not yet been clarified. This study evaluated the impact of fibrin glue on a chondrocyte loaded collagenic membrane. Methods A resorbable collagen I/III porcine derived membrane commonly employed in AMIC was used for all experiments. Chondrocytes from three difference donors were used. At 1-, 2-, 3-, 4-, 6-, and at 8-week the membranes were embedded in Mounting Medium with Dapi (ABCAM, Cambridge, UK). The Dapi contained in the mounting medium ties the DNA of the cell nucleus and emits a blue fluorescence. In this way, the spreading of the cells in the membrane can be easily monitored. The outcomes of interest were to evaluate (1) cell migration and (2) cell proliferation within the porous membrane layer. DAPI/nuclei signals were analysed with fluorescence microscope under a magnification of 100-fold. Results The no-fibrin group demonstrated greater migration of the cells within the membrane. Although migration resulted higher in the no-fibrin group at every follow-up, this difference was significant only at week 1 (P

Background: Knee pain is one of the commonest symptoms in patients who attend the Orthopaedic outpatient clinics. Chondral defects result in a painful knee. Incidence of chondral defect is reported to be between 5 and 10% over the age of 40. It is well documented that chondral defects can lead to osteoarthritis. Early detection of these lesions and cartilage repair surgery can delay the onset of osteoarthritis. The purpose of this study is to highlight the incidence, associations and correlations between opposing cartilage defects in patients who present to the knee clinic with pain. Methods: A retrospective analysis was carried out on patients who had Magnetic Resonance Imaging scans for painful knees between June 2017 and May 2019. About 227 consecutive knees were studied for the incidence of chondral defects, number of lesions, grade and size of lesion, geographical location and associated pathology in the knee. Results: All the 227 patients had chondral lesions. Most patients had 2–3 lesions (66.1%) with patellar lesions (76.6%) being the commonest followed by medial femoral condyle (59.9%). Significant correlation was found in grade and size between opposing surface lesions in patella-trochlea, Medial Femoral Condyle-Medial Tibial Plateau and Lateral Femoral Condyle-Lateral Tibial Plateau. Females were more predisposed to patella lesions. Significance between age and lesions were established. Conclusion: Incidence of cartilage defects in the knee is very high. Kissing lesions must be considered when treating cartilage lesions. Volume index could be a promising method to quantify lesions. [ABSTRACT FROM AUTHOR]

Background: The management of chondral defects of the patellofemoral joint is debated, and definitive evidence is lacking. This study systematically updated and summarised the current literature on the surgical management of isolated chondral defects of the patellofemoral joint, discussing techniques, outcome, pitfalls, and new frontiers. Methods: This systematic review was conducted according to the 2020 PRISMA statement. In August 2022, PubMed, Web of Science, Google Scholar, and Embase databases were accessed with no time constrain. All the clinical studies investigating the surgical management of chondral defects of the patellofemoral joint were retrieved. Articles which reported data on patients with advanced to severe osteoarthritis were not eligible. Only studies with a minimum 24 months follow-up were considered. Studies which mixed results of patellofemoral and tibiofemoral joints were not considered. Results: Data from 10 studies (692 procedures) were retrieved. The mean follow-up was 46.9 ± 18.2 months. The mean age of the patients was 34.0 ± 6.1 years, and the mean BMI was 25.9 ± 0.8 kg/m2. The mean duration of symptoms before the index surgery was 81.0 ± 24.0 months. The mean defect size was 3.8 ± 0.8 cm2. All the PROMs improved from baseline to last follow-up: VAS 0–10 (P = 0.04), Tegner (P = 0.02), Lysholm (P = 0.03), and International Knee Documentation Committee (P = 0.03). The rate of hypertrophy was 5.6% (14 of 251), the rate of progression to total knee arthroplasty was 2.4% (2 of 83), the rate of revision was 16.9% (29 of 136), and the rate of failure was 13.0% (16 of 123). Conclusion: Current surgical strategies may be effective to improve symptoms deriving from chondral defects of the patellofemoral joint. The limited and heterogeneous data included for analysis impact negatively the results of the present study. Further clinical studies are strongly required to define surgical indications and outcomes, and the most suitable technique. [ABSTRACT FROM AUTHOR]

Background: Some authors secured the membrane during matrix-induced autologous chondrocyte implantation (mACI) with fibrin glue or did not use a formal fixation. The real impact of fibrin glue addition on chondrocytes migration and proliferation has not yet been clarified. This study evaluated the impact of fibrin glue on a chondrocyte loaded collagenic membrane. Methods: A resorbable collagen I/III porcine derived membrane commonly employed in AMIC was used for all experiments. Chondrocytes from three difference donors were used. At 1-, 2-, 3-, 4-, 6-, and at 8-week the membranes were embedded in Mounting Medium with Dapi (ABCAM, Cambridge, UK). The Dapi contained in the mounting medium ties the DNA of the cell nucleus and emits a blue fluorescence. In this way, the spreading of the cells in the membrane can be easily monitored. The outcomes of interest were to evaluate (1) cell migration and (2) cell proliferation within the porous membrane layer. DAPI/nuclei signals were analysed with fluorescence microscope under a magnification of 100-fold. Results: The no-fibrin group demonstrated greater migration of the cells within the membrane. Although migration resulted higher in the no-fibrin group at every follow-up, this difference was significant only at week 1 (P < 0.001), 2 (P = 0.004), and 3 (P = 0.03). No difference was found at week 3, 6, and 8. The no-fibrin group demonstrated greater proliferation of the chondrocytes within the membrane. These differences were significant at week 4 (P < 0.0001), 6 (P < 0.0001), 8 (P < 0.0001). Conclusion: The use of fibrin glue over a resorbable membrane leads to lower in vitro proliferation and migration of chondrocytes. [ABSTRACT FROM AUTHOR]

Articular cartilage injuries are found in up to 60% of patients who undergo an arthroscopic knee procedure, and those that totally affect articular cartilage (grade IV) have limited regenerative capacity and extended time for recovery. 3-D scaffolds represent a novel solution to address this type of injury. Our purpose was to analyze the MRI findings and functional status of patients that underwent repair of chondral defects either by microfractures or Hyaluronan (HA) 3-D scaffolding. We conducted a retrospective study of patients with chondral defects. The outcomes analyzed in this study included anatomical changes evaluated by the Henderson score (based on MRI findings) at baseline, 6, and 12 months after surgery, and improvement in functionality evaluated by the Modified Cincinnati Knee Rating System (MCKRS) at baseline and 6 months after surgery. Clinical and demographic characteristics were similar for both groups. There was a statistically significant improvement in Henderson score for the 3-D scaffold-treated group at 6 months versus the microfracture group (p < 0.0001). Improvement in functionality, measured by the MCKRS, was more frequently found in the 3-D scaffold-treated group. In conclusion, the use of HA 3-D scaffolding was superior, with faster recovery evident 6 months after the surgery that progressed to full recovery in all patients a year after surgery. Future studies with a randomized design might help to support our findings. This study provides level III evidence.

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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]

Abstract 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.

The treatment of chondral and osteochondral defects is challenging. These types of lesions are painful and progress to osteoarthritis over time. Tissue engineering offers tools to address this unmet medical need. The use of an autologous cartilage construct consisting of hyaline cartilage chips embedded in plasma rich in growth factors (PRGF) has been proposed as a therapeutic alternative. The purpose of this study was to dig into the potential mechanisms behind the in vitro remodelling process that might explain the clinical success of this technique and facilitate its optimisation. Chondrocyte viability and cellular behaviour over eight weeks of in vitro culture, type II collagen synthesis, the dual delivery of growth factors by hyaline cartilage and PRGF matrix, and the ultrastructure of the construct and its remodelling were characterised. The main finding of this research is that the cartilage fragments embedded in the three-dimensional PRGF scaffold contain viable chondrocytes that are able to migrate into the fibrin network, proliferate and synthesise extracellular matrix after the second week of in vitro culture. The characterization of this three-dimensional matrix is key to unravelling the molecular kinetics responsible for its efficacy.

Equine osteoarthritis (OA) leads to cartilage degradation with impaired animal well-being, premature cessation of sport activity, and financial losses. Mesenchymal stem cell (MSC)-based therapies are promising for cartilage repair, but face limitations inherent to the cell itself. Soluble mediators and extracellular vesicles (EVs) secreted by MSCs are the alternatives to overcome those limitations while preserving MSC restorative properties. The effect of equine bone marrow MSC secretome on equine articular chondrocytes (eACs) was analyzed with indirect co-culture and/or MSC-conditioned media (CM). The expression of healthy cartilage/OA and proliferation markers was evaluated in eACs (monolayers or organoids). In vitro repair experiments with MSC-CM were made to evaluate the proliferation and migration of eACs. The presence of nanosized EVs in MSC-CM was appraised with nanoparticle tracking assay and transmission electron microscopy. Our results demonstrated that the MSC secretome influences eAC phenotype by increasing cartilage functionality markers and cell migration in a greater way than MSCs, which could delay OA final outcomes. This study makes acellular therapy an appealing strategy to improve equine OA treatments. However, the MSC secretome contains a wide variety of soluble mediators and small EVs, such as exosomes, and further investigation must be performed to understand the mechanisms occurring behind these promising effects. [ABSTRACT FROM AUTHOR]

A healthy articular cartilage is paramount to joint function. Cartilage defects, whether acute or chronic, are a significant source of morbidity. This review summarizes various imaging modalities used for cartilage assessment. While radiographs are insensitive, they are still widely used to indirectly assess cartilage. Ultrasound has shown promise in the detection of cartilage defects, but its efficacy is limited in many joints due to inadequate visualization. CT arthrography has the potential to assess internal derangements of joints along with cartilage, especially in patients with contraindications to MRI. MRI remains the favored imaging modality to assess cartilage. The conventional imaging techniques are able to assess cartilage abnormalities when cartilage is already damaged. The newer imaging techniques are thus targeted at detecting biochemical and structural changes in cartilage before an actual visible irreversible loss. These include, but are not limited to, T2 and T2* mapping, dGEMRI, T1ρ imaging, gagCEST imaging, sodium MRI and integrated PET with MRI. A brief discussion of the advances in the surgical management of cartilage defects and post-operative imaging assessment is also included.

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]

Introduction: Autologous chondrocyte implantation (ACI) has undergone several technical modifications. Objectives: To compare clinical outcomes and graft survivorship between ''first-generation'' periosteum-covered ACI (ACI-P) and ''second-generation'' collagen membrane ACI (ACI-C). Methods: A total of 400 consecutive ACI cases performed by a single surgeon were reviewed. Of the total, 200 were treated with ACI-P and 200 ACI-C. Patients with a minimum follow-up of 2 years were included (ACI-P, n = 112; ACI-C, n = 94). A separate long-term analysis was completed with a mean follow-up of 9 ± 1.8 years in the ACI-P group and 12 ± 2.2 years in the ACI-C group. Clinical outcomes and graft survivorship were compared at both follow-up intervals. Predictors of treatment failures and subsequent surgical procedures (SSPs) were identified. Results: Treatment failures were significantly greater among ACI-P cases compared to ACI-C, P = .007 with a greater proportion of cases with disease progression in the ACI-P cohort, P = .022. SSPs were greater in the ACI-P cohort, P < .001. Debridement for symptomatic hypertrophy was the most frequently performed SSP among ACI-P cases. ACI generation and prior marrow stimulation were significant predictors of treatment failures and SSPs. There were significant mean improvements in patient subjective responses within treatment groups. No differences in patient subjective responses were observed between ACI generations. Cumulative graft survivorship was greater in the ACI-C cohort (P = .024). Conclusions: The use of ACI-C improved clinical outcomes with a reduction in treatment failures, SSPs, and graft hypertrophy, allowing the surgeon to treat a greater number of bipolar and multiple lesion cases with similar functional outcomes when compared to ACI-P.

Introduction: Full-thickness chondral defects at the knee joint predispose to the beginning of a degenerative process which final consequence is the compartment collapse and finally the deviation to varus, because the cartilage of the medial femoral condyle is the most frequently affected area. Likewise, people with these chondral defects are more likely to develop tricompartmental osteoarthritis, reason why early surgical management should be the treatment of choice. The aim of this study was to compare the pre- and post-operative lower limb alignment (mechanical axis), in cases of full-thickness chondral defects of the femoral medial condyle that have been managed by means of a prosthetic focal inlay resurfacing, at a minimum follow-up of five years. Methods: A retrospective study of patients treated for chondral defects in the medial femoral condyle was performed. The inclusion criteria were patients who had undergone a focal inlay resurfacing and minimum follow-up of 5 years. Patients that required a concomitant valguizing tibial osteotomy were finally excluded. The follow-up analysis was performed by means of radiological examinations performed prior to surgery and at the last follow-up visit. The mean limb mechanical axis of the operated knees was calculated both pre- and post-operatively, and comparisons between these two settings were performed. Results: Ten patients were included: eight men and two women. The mean age at the time of surgery was 55 (40–65) years. The mean follow-up was 9 years (range 5–15). The mean limb mechanical axis was 1.33 ± 4.16 in the pre-operative setting and 2.40 ± 5.50 in the post-operative setting (p = 0.441). Conclusion: In the setting of small to moderate size, unique femoral medial condyle full-thickness chondral lesions, filling the defect with an inlay prosthetic resurfacing may protect against the progression to varus deformity. Level of evidence: Therapeutic case series, Level IV. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

PURPOSE OF THE STUDY In patients older than 40 years of age, treatment of chondral lesions of the knee employing microfractures does not provide satisfactory outcomes. One of the contributing factors may be the age-related lack of sufficient mesenchymal stromal cells able to efficiently migrate into the desired site of the lesion. Concomitant application of mononuclear cells (MNCs) or cultured mesenchymal stem cells (MSCs) isolated from bone marrow and seeded on a 3D scaffold could provide an alternative enhancing therapeutic efficacy in these patients. The aim of our study was to assess two different sources of bone marrow for isolation of progenitor cells. To be specific, material obtained from proximal tibia and iliac crest (the commonly used bone marrow source) was compared in terms of quantity and quality of cells and their suitability for cellbased treatment of chondral lesions. MATERIAL AND METHODS Bone marrow was collected during a total knee replacement surgery from the iliac crest and the proximal metaphysis of the tibia from ten volunteers older than 40 years of age, using aspiration biopsy needles. The MNCs from the obtained material were isolated, cultured and analyzed for their phenotypic features. Both sources were compared as to the yield and viability of MNCs and MSCs as well as the ability of MSCs of chondrogenic differentiation. RESULTS The MNCs concentration/yield was significantly higher in samples from the iliac crests. Similar results were obtained with cultured MSCs after the first passage when the MSCs/MNCs ratio was compared. Nevertheless, the qualitative analysis that included MSCs immuno-phenotyping, viability and population doubling time showed no difference between the two tested bone marrow sources. DISCUSSION Particularly in older patients, therapies of chondral defects employing bone marrow-stimulating techniques result in unsatisfactory outcomes. Therefore, orthopedic surgeons have turned their attention to cell-based treatments. Bone marrow located in pelvic bone and metaphysis of long bones (distal femur, proximal tibia) contains mononuclear cells that possess features of MSCs. In accordance with other authors, quantitative differences between the cells from two anatomical locations were found in our cohort of patients. Qualitatively, however, there was no significant variability observed. We also confirmed that the metaphysis of proximal tibia is a suitable source for cultured MSCs. Moreover, in contrast to several reports, the quality of these cells does not appear to decrease with the patients age. CONCLUSIONS The iliac crest represents a superior bone marrow source for the MNCs and MSCs yield when compared with tibia. However, there was no qualitative difference between the isolated and cultured cells. The population doubling time analysis showed that the tibia is a good alternative source of MSCs which can be obtained at therapeutically relevant numbers for example for the treatment of chondral lesions of the knee. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) remains incurable in humans or horses and mesenchymal stromal/stem cells (MSCs) represent an attractive solution for producing a neocartilage substitute. However, the best MSC source still needs to be identified. This study compared the chondrogenic potential of equine MSCs derived from bone marrow (BM) and umbilical cord blood (UCB), at their undifferentiated status to check if one cell source is better proned, and after chondrogenic-induced differentiation. Chondrogenesis was induced by culture in collagen scaffold with BMP-2 + TGF-ß1 in hypoxia or normoxia. MSCs chondrogenic potential was evaluated using the mRNA and corresponding protein levels for osteogenic, hypertrophic and chondrogenic markers. MSCs characterization demonstrated that BM- and UCB-MSCs differ in proliferation and tripotencies. At undifferentiated status, they also showed differences in their expression of osteogenic, chondrogenic and hypertrophic markers. Upon chondrogenesis induction, both MSCs sources exhibited increased chondrogenic expression and produce an extracellular matrix (ECM) of better quality in hypoxia, although collagen I remained expressed. UCB-MSCs produced higher amounts of collagen II, particularly its IIB isoform, than BM-MSCs, but also collagen I and Htra1, regardless of the oxygen condition. Finally, immunohistochemistry revealed that the BM-MSCs synthesized an ECM of higher quality, regarding the more homogenous distribution of type IIB collagen, compared to UCB-MSCs. Considering collagen I as the major undesirable component in the neo-synthesis of in vitro cartilage, we recommend using BM-MSCs for horse cartilage engineering. [ABSTRACT FROM AUTHOR]

Articular cartilage defects represent an inciting factor for future osteoarthritis (OA) and degenerative joint disease progression. Despite multiple clinically available therapies that succeed in providing short term pain reduction and restoration of limited mobility, current treatments do not reliably regenerate native hyaline cartilage or halt cartilage degeneration at these defect sites. Novel therapeutics aimed at addressing limitations of current clinical cartilage regeneration therapies increasingly focus on allogeneic cells, specifically mesenchymal stem cells (MSCs), as potent, banked, and available cell sources that express chondrogenic lineage commitment capabilities. Innovative tissue engineering approaches employing allogeneic MSCs aim to develop three-dimensional (3D), chondrogenically differentiated constructs for direct and immediate replacement of hyaline cartilage, improve local site tissue integration, and optimize treatment outcomes. Among emerging tissue engineering technologies, advancements in cell sheet tissue engineering offer promising capabilities for achieving both in vitro hyaline-like differentiation and effective transplantation, based on controlled 3D cellular interactions and retained cellular adhesion molecules. This review focuses on 3D MSC-based tissue engineering approaches for fabricating “ready-to-use” hyaline-like cartilage constructs for future rapid in vivo regenerative cartilage therapies. We highlight current approaches and future directions regarding development of MSC-derived cartilage therapies, emphasizing cell sheet tissue engineering, with specific focus on regulating 3D cellular interactions for controlled chondrogenic differentiation and post-differentiation transplantation capabilities.

Introduction: Evidence on the management of chondral defects of the patella arises from studies in which the patellofemoral joint was treated together with the femorotibial joint and primary and revision settings. Furthermore, the superiority of Autologous Matrix Induced Chondrogenesis (AMIC) over microfractures (MFx) for patellar chondral defects is uncertain. Therefore, the present study compared primary isolated AMIC versus MFx for focal unipolar chondral defects of the patellar facet joints at midterm follow-up. Methods: Patients undergoing AMIC or isolated MFx surgery for borderline-sized focal unipolar chondral defects of the patellar facet joints were followed at our institution. All surgeries were performed in the same fashion by experienced surgeons. A parapatellar arthrotomy was adopted in all surgeries. The outcomes of interest were: Visual Analogic Scale (VAS), Tegner Activity Scale, International Knee Documentation Committee (IKDC), and the Lysholm scores. The Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) was assessed by a blinded radiologist, who had not been involved in the clinical management of the patients. Results: 38 patients were enrolled in the present study: 27 underwent AMIC, and 11 MFx. The mean follow-up was 45.1 months. The mean age of the patients at baseline was 34.5 years. The mean size of the defect was 2.6 cm2. The MFx cohort experienced a shorter length of the hospitalization (P = 0.008). There was no difference in terms of follow-up and previous symptoms duration, mean age, sex, side, defect size, and BMI. At last follow-up, the AMIC cohort reported greater IKDC (P = 0.01), Lysholm (P = 0.009), and Tegner (P = 0.02), along with a low rate of failure (P = 0.02). VAS was lower in the AMIC group (P = 0.002). No difference was found in the MOCART score (P = 0.09), rates of revision (P = 0.06), and arthroplasty (P = 0.2). Conclusion: The AMIC procedure achieves greater IKDC and Lysholm score, and a significant reduction of the VAS score in the management of patellar chondral defects. The Tegner scale demonstrated greater activity after AMIC procedure. Finally, the AMIC group evidenced a lower rate of failure. Similarity was found on MOCART score, rates of revision, and arthroplasty between the two procedures.

Introduction: The potential of autologous matrix-induced chondrogenesis (AMIC) to restore unipolar focal chondral defects of the knee is promising. However, the outcome compared to microfracturing (MFx) for certain defect sizes (2–3 cm2) is still uncertain. Therefore, the present study compared primary isolated AMIC versus MFx in a cohort of patients with borderline sized focal unipolar chondral defects of the knee at midterm follow-up. Methods: Patients with chondral defects of the knee who underwent AMIC or MFx were compared. An arthroscopic approach was used for MFx, and a minimally invasive parapatellar arthrotomy for AMIC. For those patients who underwent AMIC, a collagen membrane was used with fibrin glue. The patients answered independently: Visual Analogic Scale (VAS), Tegner Activity Scale, International Knee Documentation Committee (IKDC), and the Lysholm scores. Results: A total of 83 patients with a mean age of 30.2 and body mass index (BMI) of 26.9 kg/m2 were recruited. Of them, 33.7% (28 of 83) were women, and 55.4% (46 of 83 patients) had defects in the right knee. The mean length of symptoms before surgery was 43.3 months. The mean size of the defect was 2.7 cm2. The mean length of follow-up was 42.1 months. No difference was found in terms of symptoms and follow-up length, mean age and BMI, mean size of defect, sex, and side. The AMIC cohort reported greater IKCD (p > 0.0001), Lysholm (p = 0.002), VAS (p = 0.01), Tegner (p = 0.004) scores. The AMIC cohort reported lower rate of failure (p = 0.005) and revision surgery (p = 0.02). No difference was found in the rate of arthroplasty (p = 0.2). No delamination or hypertrophy were detected. Conclusion: AMIC demonstrated superiority over MFx for focal unipolar chondral defects of the knee. At approximately 40 months follow-up, the IKDC, Lysholm, and VAS scores were greater in the AMIC group. Patients treated with AMIC also demonstrated a higher level of sport activity, and lower rates of failure and revision surgeries.

Articular cartilage is a tissue characterized by its poor intrinsic capacity for self-repair. This tissue is frequently altered upon trauma or in osteoarthritis (OA), a degenerative disease that is currently incurable. Similar musculoskeletal disorders also affect horses and OA incurs considerable economic loss for the equine sector. In the view to develop new therapies for humans and horses, significant progress in tissue engineering has led to the emergence of new generations of cartilage therapy. Matrix-associated autologous chondrocyte implantation is an advanced 3D cell-based therapy that holds promise for cartilage repair. This study aims to improve the autologous chondrocyte implantation technique by using equine mesenchymal stem cells (MSCs) from bone marrow differentiated into chondrocytes that can be implanted in the chondral lesion. The optimized protocol relies on culture under hypoxia within type I/III collagen sponges. Here, we explored three parameters that influence MSC differentiation: culture times, growth factors and RNA interference strategies. Our results suggest first that an increase in culture time from 14 to 28 or 42 days lead to a sharp increase in the expression of chondrocyte markers, notably type II collagen (especially the IIB isoform), along with a concomitant decrease in HtrA1 expression. Nevertheless, the expression of type I collagen also increased with longer culture times. Second, regarding the growth factor cocktail, TGF-β3 alone showed promising result but the previously tested association of BMP-2 and TGF-β1 better limits the expression of type I collagen. Third, RNA interference targeting Col1a2 as well as Col1a1 mRNA led to a more significant knockdown, compared with a conventional strategy targeting Col1a1 alone. This chondrogenic differentiation strategy showed a strong increase in the Col2a1:Col1a1 mRNA ratio in the chondrocytes derived from equine bone marrow MSCs, this ratio being considered as an index of the functionality of cartilage. These data provide evidence of a more stable chondrocyte phenotype when combining Col1a1 and Col1a2 siRNAs associated to a longer culture time in the presence of BMP-2 and TGF-β1, opening new opportunities for preclinical trials in the horse. In addition, because the horse is an excellent model for human articular cartilage disorders, the equine therapeutic approach developed here can also serve as a preclinical step for human medicine. [ABSTRACT FROM AUTHOR]

Articular cartilage presents a poor capacity for self-repair. Its structure-function are frequently disrupted or damaged upon physical trauma or osteoarthritis in humans. Similar musculoskeletal disorders also affect horses and are the leading cause of poor performance or early retirement of sport- and racehorses. To develop a therapeutic solution for horses, we tested the autologous chondrocyte implantation technique developed on human bone marrow (BM) mesenchymal stem cells (MSCs) on horse BM-MSCs. This technique involves BM-MSC chondrogenesis using a combinatory approach based on the association of 3D-culture in collagen sponges, under hypoxia in the presence of chondrogenic factors (BMP-2 + TGF-β) and siRNA to knockdown collagen I and HtrA1. Horse BM-MSCs were characterized before being cultured in chondrogenic conditions to find the best combination to enhance, stabilize, the chondrocyte phenotype. Our results show a very high proliferation of MSCs and these cells satisfy the criteria defining stem cells (pluripotency-surface markers expression). The combination of BMP-2 + TGF-β strongly induces the chondrogenic differentiation of MSCs and prevents HtrA1 expression. siRNAs targeting Col1a1 and Htra1 were functionally validated. Ultimately, the combined use of specific culture conditions defined here with specific growth factors and a Col1a1 siRNAs (50 nM) association leads to the in vitro synthesis of a hyaline-type neocartilage whose chondrocytes present an optimal phenotypic index similar to that of healthy, differentiated chondrocytes. Our results lead the way to setting up pre-clinical trials in horses to better understand the reaction of neocartilage substitute and to carry out a proof-of-concept of this therapeutic strategy on a large animal model. [ABSTRACT FROM AUTHOR]

Purpose: To compare the diagnostic performance of three-dimensional (3D) intermediate-weighted FSE (IW-3D) and 3D hybrid T1-weighted sequences (Hy-3D) and 2D fast-spin-echo sequences (FSE) in diagnosing chondral and labral lesions at 1.5 Tesla hip MR arthrography (MRA). Materials and methods: Institutional review board approval was obtained and informed consent was waived. Ninety-two consecutive patients were evaluated. Chondral and labral lesions were retrospectively and independently evaluated by two radiologists. Intra-operative findings were used as the reference standard (arthroscopy = 73, open surgery = 19). Sensitivity (Se), specificity (Sp), and accuracy (Acc) values that obtained were compared using McNemar test. A value of p < 0.05 was considered statistically significant. Inter-observer agreement was calculated using kappa statistics. Results: Surgeons revealed 81 labrum and 44 chondral lesions, respectively. The highest Se, Sp, and Acc for Reader 1 were 96.3, 90.9, and 95.6%, respectively, in evaluating labral lesions (by reading 2D data set) and 90.9, 100, and 95.7% in evaluating chondral lesions (by reading IW-3D images). The highest Se, Sp, and Acc for Reader 2 were 93.8, 81.8, and 92.4% in evaluating labral lesions (using 2D images) and 88.6, 97.9, and 93.5%, respectively, in evaluating chondral lesions (using Hy-3D). The difference of diagnostic accuracy achieved was not significant ( p > 0.05). A near-perfect inter-observer agreement was achieved by reading 2D data set ( k = 0.88) and Hy-3D ( k = 0.83) and IW-3D ( k = 0.85). Conclusions: At 1.5 Tesla hip MRA, the accuracy of IW-3D and Hy-3D images was not significantly higher than the 2D sequences in evaluating acetabular labrum and chondral lesions. [ABSTRACT FROM AUTHOR]

Background: Conventional osteochondral allograft (OCA) matching, requiring orthotopic, size-matched condyles, and narrow surgical time windows often prohibit timely transplantation. Hypothesis: The femoral condyle radius of curvature (RoC) is an appropriate, isolated criterion for donor-host matching in fresh OCAs, potentially enhancing matching efficiency when compared with conventional matching techniques. Study Design: Descriptive laboratory study. Methods: In part 1 of this study, 3-dimensional digital reconstructions of 14 randomly selected, cadaveric distal femoral hemicondyles were performed. Each condyle was divided into anterior, middle, and posterior zones. A virtual best-fit grid was applied to each, and each zone's sagittal- and coronal-plane RoCs were determined. Seven nonorthotopic OCA transplantations were performed based on RoC matching with 1-mm tolerance, and the preoperative and postoperative surface geometry were quantified to assess the accuracy of articular surface restoration. Of note, each donor-host pair did not match by the conventional method. In part 2 of this study, 12 cadaveric distal femora were categorized by size and digitized in the aforementioned manner. Simulated circular defects measuring 20, 25, and 30 mm in diameter were introduced into each zone. OCA matches were determined based on donor and host RoCs, and the total number of potential matches (of 71 total comparisons) was recorded as a percentage for each simulated defect. Finally, the results of RoC matching were compared with the conventional method for simulated defects in all zones of both the medial and lateral femoral condyles. Results: Part 1: The mean surface deviation after OCA transplantation was -0.09 mm, with a mean maximum protrusion at any point of 0.59 mm. Part 2: Using the RoC, 20-mm defects had a 100% chance of being matched. Defects of 25 and 30 mm had a 91% and 64% chance of being matched, respectively. Compared with the conventional method, the RoC method yielded a 3.2-fold greater match rate for lesions of the medial and lateral femoral condyles (P = .02). Conclusion: This investigation shows that femoral condyle RoCs in the sagittal and coronal planes may be useful, alternative matching criteria, expanding on current standards. Clinical Relevance: These matching criteria may increase the number of available matches, reduce wait times for patients, and reduce the number of wasted grafts. [ABSTRACT FROM AUTHOR]

Articular cartilage is a tissue characterized by its poor intrinsic capacity for self-repair. This tissue is frequently altered upon trauma or in osteoarthritis (OA), a degenerative disease that is currently incurable. Similar musculoskeletal disorders also affect horses and OA incurs considerable economic loss for the equine sector. In the view to develop new therapies for humans and horses, significant progress in tissue engineering has led to the emergence of new generations of cartilage therapy. Matrix-associated autologous chondrocyte implantation is an advanced 3D cell-based therapy that holds promise for cartilage repair. This study aims to improve the autologous chondrocyte implantation technique by using equine mesenchymal stem cells (MSCs) from bone marrow differentiated into chondrocytes that can be implanted in the chondral lesion. The optimized protocol relies on culture under hypoxia within type I/III collagen sponges. Here, we explored three parameters that influence MSC differentiation: culture times, growth factors and RNA interference strategies. Our results suggest first that an increase in culture time from 14 to 28 or 42 days lead to a sharp increase in the expression of chondrocyte markers, notably type II collagen (especially the IIB isoform), along with a concomitant decrease in HtrA1 expression. Nevertheless, the expression of type I collagen also increased with longer culture times. Second, regarding the growth factor cocktail, TGF-β3 alone showed promising result but the previously tested association of BMP-2 and TGF-β1 better limits the expression of type I collagen. Third, RNA interference targeting Col1a2 as well as Col1a1 mRNA led to a more significant knockdown, compared with a conventional strategy targeting Col1a1 alone. This chondrogenic differentiation strategy showed a strong increase in the Col2a1:Col1a1 mRNA ratio in the chondrocytes derived from equine bone marrow MSCs, this ratio being considered as an index of the functionality of cartilage. These data provide evidence of a more stable chondrocyte phenotype when combining Col1a1 and Col1a2 siRNAs associated to a longer culture time in the presence of BMP-2 and TGF-β1, opening new opportunities for preclinical trials in the horse. In addition, because the horse is an excellent model for human articular cartilage disorders, the equine therapeutic approach developed here can also serve as a preclinical step for human medicine.

Increased muscle co-contraction during gait is common in individuals with knee pathology, and worrisome as it is known to amplify tibiofemoral compressive forces. While knees with articular cartilage defects (ACD) are more vulnerable to compressive forces, muscle co-contraction has never been reported in this population. The purpose of this study was to evaluate the extent to which individuals with ACDs in the knee demonstrate elevated quadriceps to hamstrings muscle co-contraction on the involved limb during gait compared to the uninvolved limb and to healthy controls. We also explored the impact of participant characteristics and knee impairments on co-contraction. Twenty-nine individuals with full-thickness knee ACDs (ACD group) and 19 healthy adults (control group) participated in this study. Participants performed five gait trials at self-selected speed, during which activity of the quadriceps and hamstrings muscles were collected with surface electromyography. Three-dimensional motion capture was used to define phases of gait. Quadriceps strength and self-reported outcomes were also assessed in the same session. There were no differences in quadriceps: hamstrings co-contraction between the ACD and control groups, or between the involved and uninvolved limb for the ACD group. For both ACD and control groups, co-contraction was highest in early stance and lowest in late stance. Quadriceps strength was consistently the strongest predictor of muscle co-contraction in both the ACD and the control groups, with individuals with lower strength demonstrating greater co-contraction. Further study is needed to understand the effect of increased muscle co-contraction on joint compressive forces in the presence of varied quadriceps strength. [ABSTRACT FROM AUTHOR]

Purpose: Hip arthroscopy is a safe and reproducible method for treating femoroacetabular impingement (FAI) and has evolved greatly in recent years. But little is known about the influences on the outcome after surgery. The aims of the current study were to elucidate (1) which parameters can be used as a marker for the presence of chondral and labral lesions, (2) the postoperative clinical outcome, and (3) at which time after surgery recovery occurs.Methods: A prospective study was performed with 177 patients who underwent hip arthroscopy because of cam-type FAI. The patients were examined preoperatively as well as 6 weeks and 6 months postoperatively, and their condition was rated according to the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and the Non-Arthritic Hip Score (NAHS). Statistical analyses were performed to evaluate the influence of independent factors such as "patient age," "pain duration before surgery" on the clinical outcome, and the appearance of chondral or labral defects.Results: The NAHS and WOMAC scores showed a significant enhancement 6 weeks after surgery. Only the NAHS showed a further improvement after 6 months. A positive correlation with the dependent variable "chondral lesion" was evaluated for the independent variables "pain duration before surgery," "preoperative NAHS," and "labrum lesion". Using ROC analysis, the optimal cutoff value of "pain duration before surgery" as a predictor was 9.5 months, for the NAHS 42.5 points. For the dependent variable, "6-month postoperative NAHS" significant correlations for the independent variables "age" and "pain duration before surgery" were revealed with a cutoff value of 55.5 years, respectively, 23.5 months.Conclusions: It was concluded from the results that the date of surgery is relevant for the appearance of chondral defects. Patient age is a further relevant factor for clinical outcome. Recovery after hip arthroscopy takes place mainly in the first 6 weeks after surgery.Level Of Evidence: Therapeutic study, Level III. [ABSTRACT FROM AUTHOR]

Chondral defects of the knee are quite common, affecting an estimated 10% to 12% of the population. Symptomatic chondral defects are thought to be persistent and possibly progressive. Less is known about the natural history of asymptomatic chondral lesions. Traditional treatment of chondral lesions has involved arthroscopic debridement with a mechanical shaver. Radiofrequency chondroplasty has been explored as a possible alternative or adjuvant to mechanical chondroplasty. The role of chondroplasty in the setting of knee osteoarthritis is more controversial. Early studies demonstrated promising results of arthroscopic debridement in the context of knee arthritis. However, publications in the last 10 to 15 years have brought into question the role of arthroscopic debridement in the setting of knee osteoarthritis. The purpose of this chapter is to explore the role of arthroscopic debridement in the treatment of chondral defects. [ABSTRACT FROM AUTHOR]

Chondral lesions are currently considered in the hip as a consequence of trauma, osteonecrosis, dysplasia, labral tears, loose bodies, dislocation, previous slipped capital femoral epiphysis and Femoro-Acetabular-Impingement (FAI). The management of chondral lesions is debated and several techniques are described. The physical examination must be carefully performed, followed by radiographs and magnetic resonance imaging (MRI). Differential diagnosis with other pathologies must be considered. Debridement is indicated in patients younger than 50 years with a chondropathy of 1st or 2nd degree. Microfractures are indicated in patients younger than 50 years with a chondropathy of 3rd or 4th degree less than 2 cm2. Matrix-Induced Autologous Chondrocyte Implantation (MACI) and Autologous Matrix-Induced Chondrogenesis (AMIC) procedures are indicated in patients with full-thickness symptomatic 3rd–4th degree chondral defects, extended 2 cm2 or more. The AMIC procedure has the advantage of a one-step procedure and much less expense. Microfragmented adipose tissue transplantation (MATT) is indicated for the treatment of delamination and 1st and 2nd degree chondral lesions, regardless of the age of the patient. Chondral defects are effective when the joint space is not compromised. When the Tonnis classification is two or greater, treatment of chondral lesions should be considered ineffective.

Actively steering the chondrogenic differentiation of mesenchymal stromal cells (MSCs) into either permanent cartilage or hypertrophic cartilage destined to be replaced by bone has not yet been possible. During limb development, the developing long bone is exposed to a concentration gradient of oxygen, with lower oxygen tension in the region destined to become articular cartilage and higher oxygen tension in transient hypertrophic cartilage. Here, we prove that metabolic programming of MSCs by oxygen tension directs chon-drogenesis into either permanent or transient hyaline cartilage. Human MSCs chondrogenically differentiated in vitro under hypoxia (2.5% O2) produced more hyaline cartilage, which expressed typical articular cartilage biomarkers, including established inhibitors of hypertrophic differentiation. In contrast, normoxia (21 % O2) prevented the expression of these inhibitors and was associated with increased hypertrophic differentiation. Interestingly, gene network analysis revealed that oxygen tension resulted in metabolic programming of the MSCs directing chondrogenesis into articular- or epiphyseal cartilage-like tissue. This differentiation program resembled the embryological development of these distinct types of hyaline cartilage. Remarkably, the distinct cartilage phenotypes were preserved upon implantation in mice. Hypoxia-preconditioned implants remained cartilaginous, whereas normoxia-preconditioned implants readily underwent calcification, vascular invasion, and subsequent endochondral ossification. In conclusion, metabolic programming of MSCs by oxygen tension provides a simple yet effective mechanism by which to direct the chondrogenic differentiation program into either permanent articular-like cartilage or hypertrophic cartilage that is destined to become endochondral bone. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies report professional athletes return to play following arthroscopic microfracture of the hip for chondral defects. Our hypothesis is that professional hockey players undergoing arthroscopic microfracture for chondral defects of the hip achieve the same performance they had pre-injury and compared to matched controls. Methods: Seventeen professional hockey players underwent arthroscopic microfracture for an Outerbridge grade IV chondral lesion. Concomitant procedures for labral pathology or FAI were included. Performance data for the full season preceding and following index procedure were analysed, in addition to two matched control players per subject. Data were collected at two points, 2 years apart. Results: Eighty-two per cent (14/17) of players who underwent arthroscopic microfracture returned to play. The year prior to injury for the 14 players who returned was compared to the average of their individual controls. There was no statistical difference between the groups for age, number of seasons in the league, games played, time on ice, points, save percentage, and shots against goal. Post-operatively, there was no statistical difference between the treatment and control groups regarding performance measures. There was a trend towards a decrease in games played and points post-operatively compared with controls. The treatment group decreased 11 games played, while the controls decreased five games. The treatment group also decreased 14 points, while the controls decreased three points for the season. Conclusions: Professional hockey players with a discrete, full-thickness chondral defect of the hip are able to return to elite performance level following an arthroscopic microfracture procedure when compared to pre-injury outcomes and controls. Level of evidence: III. [ABSTRACT FROM AUTHOR]

The article presents a study which investigated the effectiveness of a one-step surgery with multipotent stem cells for the treatment of large full-thickness chondral defects of the knee. In the study, bone marrow-obtained multipotent stem cells (MSC) and a second-generation matrix were used. Among the methods used in the study are radiographs, magnetic resonance imaging (MRI) and visual analog scale (VAS).

Purpose: The purpose of this study was to describe the practice of microfracture surgery for knee chondral defects among Canadian orthopedic surgeons. Methods: All orthopedic surgeon members of the Canadian Orthopaedic Association were invited to participate in a survey, designed to explore the microfracture technique used by orthopedic surgeons in the treatment for knee chondral defects The primary outcome measure was an emailed 26-item questionnaire, which explored indications for microfracture surgery, surgical techniques, types of postoperative rehabilitation regimes used and assessment of outcome. In addition, responses were compared between orthopedic surgeons with a sports medicine practice to surgeons with a non-sports medicine practice. Results: The survey response rate was 24.6% (299/1,216), with 131 regularly performing microfracture. 41% of surgeons indicated that they had no upper limit for age at the time of surgery, and 87% indicated no upper limit for body mass index. The majority of respondents (97%) resected cartilage back to a stable margin, while 69% of respondents removed the calcified cartilage layer prior to creating holes. Only 11% of respondents used continuous passive motion (CPM) postoperatively, and 39% did not restrict weight bearing. Sports surgeons were more likely than non-sports surgeons to remove the calcified cartilage layer, use a 45° pick, use CPM and restrict weight bearing postoperatively (all P values < 0.05). Conclusions: This survey on microfracture for knee chondral defects revealed widespread variation among surgeons regarding the indications for surgery, surgical technique, postoperative rehabilitation and assessment of outcome. Sports surgeons demonstrate better evidence-based practice than non-sports surgeons for a few important parameters. Level of evidence: Cross-sectional survey, Level II. [ABSTRACT FROM AUTHOR]

Purpose: Articular resurfacing by treatment of chondral defects may include chondral abrasion, autologous chondrocyte Implantation (ACI), matrix-induced chondrocyte transplantation (MACT) or osteochondral autologous transplantation (OATS). This technical note describes the method of autologous matrix-induced chondrogenesis (AMIC), a one-step procedure combining subchondral microfracture with the fixation of a collagen I/III membrane with fibrin glue or sutures. Methods: This is a technical note on the AMIC procedure and its further development. Results and conclusion: This method is applied primarily in chondral or osteochondral lesions of the knee. Indications and contraindications are provided; the technique is described. The further development of AMIC is described with an increased focus on the subchondral zone and the complex of cartilage and bone, the osteochondral unit, which receives increased attention in cartilage research. Level of evidence: IV. [ABSTRACT FROM AUTHOR]

Abstract: Articular cartilage lesions can hardly be regenerated spontaneously in vivo, remain a challenging problem for orthopedic surgeons. Various techniques have been used to treat this pathology with variable success rates. In recent years, however, regenerative techniques, such as autologous chondrocyte implantation, have emerged as possible solutions for the treatment of chondral defects. The use of classic autologous chondro-cyte implantation (first generation) has been associated with several limitations. To overcome these problems, a recent powerful cell based tissue engineering therapy has developed, Chondron™ as a commercial product of third generation autologous chondrocyte implantation. It consists of mixture of biodegradable and biocompatible gel with in vitro cultured autologous chondrocytes. This procedure avoids the use of periosteal flap, further simplifies the surgical procedure with limited time of operation with an arthroscopic procedure. Thus, the surgical morbidity and the recovery time for the patient are extremely reduced with no complications related to septic conditions and periosteal flap. The clinical outcomes of Chondron™ ACI have shown positively significant results. [Copyright &y& Elsevier]

Molecular and supramolecular design of bioactive biomaterials could have a significant impact on regenerative medicine. Ideal regenerative therapies should be minimally invasive, and thus the notion of self-assembling biomaterials programmed to transform from injectable liquids to solid bioactive structures in tissue is highly attractive for clinical translation. We report here on a coassembly system of peptide amphiphile (PA) molecules designed to form nanofibers for cartilage regeneration by displaying a high density of binding epitopes to transforming growth factor β-1 (TGFβ-1). Growth factor release studies showed that passive release of TGFβ-1 was slower from PA gels containing the growth factor binding sites. In vitro experiments indicate these materials support the survival and promote the chondrogenic differentiation of human mesenchymal stem cells. We also show that these materials can promote regeneration of articular cartilage in a full thickness chondral defect treated with microfracture in a rabbit model with or even without the addition of exogenous growth factor. These results demonstrate the potential of a completely synthetic bioactive biomaterial as a therapy to promote cartilage regeneration. [ABSTRACT FROM AUTHOR]

Surgical treatment for chondral defects of the knee in competitive running and jumping athletes remains controversial. This study evaluated the performance outcomes of professional basketball players in the National Basketball Association (NBA) who underwent microfracture. Data from 24 professional basketball players from 1997 to 2006 was obtained and analyzed. NBA player efficiency ratings (PER) were calculated for two seasons before and after injury. A control group of 24 players was used for comparison. Study group and control group demographics including age, NBA experience, and minutes per game demonstrated no statistical difference. Mean time to return to an NBA game was 30.0 weeks from the time of surgery. The first season after returning to competition PER and minutes per game decreased by 3.5 ( P < 0.01) and 4.9 min ( P < 0.05), respectively. The 17 players who continued to play two or more seasons after surgery, the average reduction in their PER and minutes per game was 2.7 ( P > 0.05) and 3.0 min ( P < 0.26), respectively. A multivariant comparison versus controls demonstrated that power rating during the 2 years after surgery decreased by 3.1 ( P < 0.01); while minutes per game decreased by 5.2 ( P < 0.001). Twenty-one percent ( n = 5 of 24) of the players treated with microfracture did not return to competition in an NBA game. On return to competition player performance and minutes per game are diminished. [ABSTRACT FROM AUTHOR]

Although clinical trials have proved that the use of glycosamide in humans is encouraging, the data from veterinary medicine are scarce and controversal. That is why the present study wants to evaluate the effect of glycosamide as food supplement in dogs with surgically induced chondral defects by analysing some parameters of the synovial fluid. 5 month after surgery the evaluation of the average number of cells/ μL, of the mononuclear percentage and the neutrophils, of the cell morphlolgy, of the sinoval fluid have not showed significat differences at the batch using glycosamide as compared with the batch that was on a glycosamide free diet. [ABSTRACT FROM AUTHOR]

The article focuses on the basic science, surgical techniques and clinical outcomes of the third-generation cell-based technologies for cartilage repair. It states that cell-based therapies such as autologous chondrocyte implantation (ACI) hold promise for cartilage regeneration, however, these techniques still do not predictably result in hyaline cartilage formation. It mentions that these new procedures use three novel approaches, including chondro-inductive or chondro-conductive matrix, use of allogeneic cells, and techniques to mechanically condition the developing tissue before surgical application to enhance the material properties and maturation of the implant.