Unicompartmental osteoarthritis: High survival rate with a combined mechanical and biological salvage approach as alternative to metal resurfacing: Results at minimum 10 years of follow-up.

PURPOSE: The aim of this study was to prospectively evaluate the long-term clinical results and failure rate of patients treated with complex salvage procedures using a combined mechanical and biological approach to address unicompartmental knee osteoarthritis (OA) and postpone the need for joint replacement. METHODS: Thirty-nine patients (40.3 ± 10.9 years old) affected by unicompartmental OA (Kellgren-Lawrence 3) in stable joints underwent a personalized surgical treatment depending on the specific requirements of the affected compartment, including high tibial osteotomy, osteochondral scaffold, meniscal scaffold and meniscal allograft transplantation. Patients were evaluated with the International Knee Documentation Committee (IKDC), Visual Analogue Scale (VAS) and Tegner scores before surgery, at 3 years and a minimum of 10 years of follow-up. RESULTS: A significant improvement was observed over time in all scores but worsened at the final follow-up. The IKDC subjective score improved from 46.9 ± 16.2 to 79.8 ± 16.4 at 3 years (p < 0.0005) and then decreased to 64.5 ± 21.4 (p = 0.001) at 12 years. A similar trend was confirmed for VAS and Tegner scores. Only two patients subsequently underwent knee arthroplasty, and nine more patients were considered clinical failure, for a cumulative surgical and clinical failure rate of 28.2% at the final follow-up. CONCLUSION: A personalized, joint-preserving, combined mechanical and biological approach, addressing alignment as well as meniscal and cartilage lesions, is safe and effective, providing a clinical benefit and delaying the need for arthroplasty in young patients affected by unicompartmental knee OA. At the final evaluation, the clinical improvement decreased, but more than two-thirds of the patients still benefited from this treatment at a long-term follow-up. LEVEL OF EVIDENCE: Level IV case series.

Cell-free biomimetic osteochondral scaffold for the treatment of knee articular surface lesions: Clinical outcomes differ based on patient and lesion characteristics.

PURPOSE: A cell-free biomimetic osteochondral scaffold was developed to treat cartilage knee lesions, with positive clinical results documented in small case series. However, clear evidence on patient and lesion characteristics that might affect the outcome is still lacking. The aim of this study is to analyse a large cohort of patients treated with this scaffold to investigate factors that could influence the clinical outcome. METHODS: Two hundred and three patients (mean age 30.7 ± 10.9 years) treated with this scaffold were prospectively evaluated at baseline, 6-, 12- and 24-month follow-up. The clinical outcome was analysed using the International Knee Documentation Committee (IKDC) score, and the activity level was assessed with the Tegner score. The influence of patient and lesion characteristics on clinical outcomes was analysed. RESULTS: Mild and severe adverse reactions were found in 39.0% and 1.5% of patients, respectively. The failure rate was 2.0%, increasing to 12.3% when including also clinical failures. The IKDC subjective score increased from 43.3 ± 15.9 to 61.0 ± 16.2 at 6 months, 68.3 ± 18.5 at 12 months and 73.8 ± 18.3 at 24 months (p < 0.0005). The Tegner improved from 2.5 ± 1.7 to 4.2 ± 1.7 at 24 months (p < 0.0005), without reaching the pre-injury level (6.0 ± 2.2) (p < 0.0005). The IKDC objective score changed from 68.5% normal and nearly normal knees before the treatment to 90.1% at 24 months. At 24 months, age showed a correlation with the IKDC subjective score (ρ = -0.247; p < 0.0005), women had a lower score (p < 0.0005), as well as patients with patellar lesions (p = 0.002). Previous surgery correlated with lower results (p = 0.003), while better results were found in osteochondritis dissecans (OCD) compared to degenerative lesions (p = 0.001). CONCLUSION: This cell-free biomimetic scaffold is a safe and effective treatment for cartilage knee lesions, offering positive clinical results at 2 years with a low failure rate. Better outcomes were observed in younger patients, in lesions of the femoral condyles and in OCD, while joints affected by patellar lesions, patients who underwent previous knee surgery, and women may expect lower results. LEVEL OF EVIDENCE: III, Cohort study.

Platelet-rich plasma injections for the management of knee osteoarthritis: The ESSKA-ICRS consensus. Recommendations using the RAND/UCLA appropriateness method for different clinical scenarios.

PURPOSE: The aim of this consensus was to develop evidence- and expert-based patient-focused recommendations on the appropriateness of intra-articular platelet-rich plasma (PRP) injections in different clinical scenarios of patients with knee osteoarthritis (OA). METHODS: The RAND/UCLA Appropriateness Method was used by the European Society of Sports Traumatology, Knee Surgery, and Arthroscopy (ESSKA), as well as the International Cartilage Regeneration and Joint Preservation Society (ICRS) to reach a consensus and produce recommendations for specific patient categories combining best available scientific evidence with the collective judgement of a panel of experts. RESULTS: Scenarios were defined based on first treatment vs first injective treatment vs second injective treatment, age (<50/50-65/66-80/>80), tibiofemoral vs patellofemoral involvement, OA level (Kellgren-Lawrence/KL 0-I/II-III/IV), and joint effusion (dry knee, minor-mild or major effusion). Out of 216 scenarios, in 84 (38.9%) the indication was considered appropriate, in 9 (4.2%) inappropriate and in 123 (56.9%) uncertain. The parameters associated with the highest consensus were PRP use after failed injective treatments (62.5%), followed by PRP after failed conservative treatments and KL 0-III scenarios (58.3%), while the highest uncertainty was found for PRP use as first treatment and KL IV OA (91.7% and 87.5% of uncertain scenarios, respectively). CONCLUSION: This ESSKA-ICRS consensus established recommendations on the appropriateness or inappropriateness of PRP injections for the treatment of knee OA, providing a useful reference for clinical practice. PRP injections are considered appropriate in patients aged ≤80 years with knee KL 0-III OA grade after failed conservative non-injective or injective treatments, while they are not considered appropriate as first treatment nor in KL IV OA grade. LEVEL OF EVIDENCE: Level I.

Single-plug osteochondral autograft transplantation for knee osteochondritis dissecans: Clinical improvement and long-term survivorship at a minimum ten year follow-up.

PURPOSE: Osteochondritis dissecans (OCD) can lead to detrimental effects in the affected joints. Osteochondral autologous transplantation (OAT) allows to restore the articular surface with an autologous osteochondral unit. While short-term results are documented, there is a lack of long-term data. Aim of this study was to analyze the long-term clinical results of single-plug OAT for the treatment of knee OCD. METHODS: Twenty patients (14 men, 6 women) were treated with single plug-OAT. Mean age was 23.6 ± 9.9 years and BMI was 23.3 ± 3.6 kg/m2. Lesion size was 2.3 ± 1.6 cm2 and defects included 14 medial femoral condyles (MFC) and 6 lateral femoral condyles (LFC). Patients were followed up prospectively at baseline, 24 months, 60 months, and at minimum ten years (12.6 ± 2.0 years) using the IKDC subjective score and through an overall judgment on treatment satisfaction. The activity level was evaluated with the Tegner score and adverse events and failures were also recorded. Factors influencing the clinical outcomes, including age, sex, BMI, lesions size, and lesion location were also investigated. RESULTS: No severe adverse events and no surgical failures were reported and 85.0% of patients were satisfied at a minimum ten year follow-up. Subjective IKDC showed a significant and stable improvement at all follow-ups, passing from 45.3 ± 16.5 at baseline to 73.7 ± 16.6 at 24 months (p < 0.0005), to 72.9 ± 16.6 at 60 months (p < 0.0005), and to 74.1 ± 20.8 at long-term follow-up (p < 0.0005). Patients with OCD lesions localized on the LFC obtained lower results compared to those with MFC lesions at two years and five years (p = 0.034 and p = 0.023). The highest long-term scores were obtained in patients with lesion size lower than 2 cm2 (89.1 ± 8.8) compared to patients with lesion size between 2 and 4 cm2 (69.2 ± 15.7), and patients with lesion size larger than 4 cm2 (63.8 ± 34.6). CONCLUSIONS: OAT is a suitable technique to treat knee OCD in young patients and offers a high patient satisfaction and a significant improvement in terms of clinical subjective scores, with results remaining stable over time, although without reaching the pre-injury activity level. No severe adverse events and no surgical failures have been documented confirming OAT as a valid treatment option, although the best long-term results for lesions smaller than 2 cm2 and for MFC lesions should be considered when choosing this procedure to address knee OCD lesions.

Chitosan based scaffold applied in patellar cartilage lesions showed positive clinical and MRI results at minimum 2 years of follow up.

PURPOSE: New scaffold-based cartilage regeneration techniques have been developed to improve the results of microfractures also in complex locations like the patello-femoral joint. The aim of this study was to analyse the results obtained in patellar lesions treated with a bioscaffold,  a mixture composed by a chitosan solution, a buffer, and the patient's whole blood  which forms a stable clot into the lesion. METHODS: Fifteen patients with ICRS grade 3-4 cartilage lesions of the patellar surface were treated with a chitosan bioscaffold. Fourteen patients were clinically and radiologically evaluated prospectively for a minimum follow-up of 2 years with IKDC, KOOS, Tegner score, and MRI. The mean age of patients at the time of surgery was 31.8 ± 11.9 and nine patients presented degenerative aetiology, four patients with previous trauma, and 1 patient with osteochondritis dissecans.  RESULTS: The IKDC subjective score improved from 46.2 ± 19.3 preoperatively to 69.5 ± 20.3 (p < 0.05) and 74.1 ± 23.2 (p < 0.05) at 12 and 24 months, respectively. Also KOOS Pain, KOOS Sport/Rec and KOOS QOL showed a significant improvement from baseline to 12 months and to the final follow-up. MRI evaluation showed a complete filling of the cartilage defect at the final follow-up in 70% of the lesions, obtaining a total MOCART 2.0 score of 71.5 ± 13.6 at 24 months after surgery. CONCLUSION: Chondral patellar lesions represent a complex pathology, with lower results compared to other sites. This bioscaffold represents a safe surgical treatment providing a significant clinical improvement at 24 months in the treatment of patellar cartilage lesions. LEVEL OF EVIDENCE: IV.

Combined subchondral and intra-articular injections of bone marrow aspirate concentrate provide stable results up to 24 months.

PURPOSE: The aim of this study was to evaluate the clinical and imaging findings up to 24 months of follow-up in patients treated with combined subchondral and intra-articular bone marrow aspirate concentrate (BMAC) injections for the treatment of knee osteoarthritis (OA). METHODS: Thirty consecutive patients (19 males, 11 females) aged between 40 and 75 years (mean age 56.4 ± 8.1 years) with unilateral symptomatic knee OA (Kellgren-Lawrence 2-3) were included in the study. Patients were treated with combined intra-articular and subchondral bone BMAC injections (total 9 ml) under fluoroscopic control. IKDC subjective score, VAS for pain, KOOS, and EQ-VAS were prospectively evaluated up to 24 months. Radiographs were performed at baseline and at 24 months after the procedure. MRI was evaluated with the WORMS score at baseline, 6-12 months, and 24 months of follow-up. The statistical analysis was performed using SPSS v.19.0 and for all tests p < 0.05 was considered significant. RESULTS: No major complications and a 13% failure rate were reported. The IKDC subjective score remained stable from 62.6 ± 19.4 at 12 months to 63.4 ± 17.1 at 24 months (both p < 0.0005 compared to baseline, 40.5 ± 12.5). Similar improvements were reported for all KOOS subscales, while EQ-VAS did not report any significant improvement. VAS pain worsened from 3.0 ± 1.9 at 12 months to 4.4 ± 1.8 at the final follow-up (p = 0.0001), although remaining lower compared to the baseline value of 6.3 ± 1.8 (p = 0.002). The radiographic evaluation did not reveal signs of improvement or deterioration of the OA grade. The MRI findings showed a worsening in marginal osteophytes and synovitis, but a significant reduction of bone marrow edema at 24 months (p < 0.0005). CONCLUSION: Combined intra-articular and subchondral BMAC injections provided clinical and imaging benefits up to 24 months for the treatment of symptomatic knee OA, with durable clinical results, a low failure rate, and a significant reduction of bone marrow edema.

Pure Platelet and Leukocyte-Platelet-Rich Plasma for Regenerative Medicine in Orthopedics-Time- and Preparation-Dependent Release of Growth Factors and Effects on Synovial Fibroblasts: A Comparative Analysis.

Intra-articular injections of autologous platelet concentrates are considered capable to enhance the healing of cartilage lesions, alleviate joint inflammation, and relieve other musculoskeletal pathological conditions. The aim of this study was to analyze the soluble fractions obtained from platelet-rich plasma (pure- and leukocyte-PRP) to compare time- and preparation-dependent modifications of growth factor concentrations and the supporting activity of the two preparations on synovial fibroblast growth and hyaluronic acid (HA) production in vitro. The release kinetics of FGF-2, SDF-1, VEGF, HGF, EGF, PD GF-AB/BB, IGF-1, VCAM-1, and TGF-ß isoforms were followed up to 168 h after PRP activation, and their amounts were determined by multiplex-beads immunoassay. Synovial cell growth and supernatant HA production were respectively analyzed by Alamar Blue assay and ELISA. Time-dependent modifications grouped molecules in three peculiar patterns: one reaching the highest concentrations within 18 h and decreasing afterwards, another progressively increasing up to 168 h, and the last peaking at the central time points. Synovial fibroblast growth in response to L-PRP and P-PRP revealed differences over time and among added concentrations. Both preparations displayed a preserved supporting capacity of HA synthesis.

The 50 most-cited clinical articles in cartilage surgery research: a bibliometric analysis.

PURPOSE: Articular cartilage lesions remain a challenge for orthopedic surgeons. The identification of the most important articles can help identifying the most influential techniques of the past, the current prevalent focus, and emerging strategies. The aim of this study was to identify milestones and trends in cartilage research. METHODS: This study is a bibliometric analysis based on published articles. All citation count data included in the "Scopus database" were used to identify eligible studies up to December 2020. The 50 most-cited articles on cartilage surgery were ranked based on the citation count and analyzed regarding citation density and quality (Coleman score and RoB 2.0 tool). A further search was performed to identify the most promising clinical studies among the latest publications on cartilage surgery. RESULTS: Different kinds of cartilage treatments were investigated in the 50 most-cited clinical articles. Regenerative techniques with chondrocytes were the most reported with a total of 23 articles, followed by microfracture technique in 17 articles and mosaicplasty or osteochondral autograft transplantation (OAT) in 11. Forty-five articles focused on the knee. A higher citation density was found in the most recent articles (p = 0.004). The study of the most promising landmarks of the most recent articles showed new cell-free or tissue engineering-based procedures and an overall increasing quality of the published studies. CONCLUSION: This bibliometric analysis documented an increasing interest in cartilage surgery, with efforts toward high-quality studies. Over the years, the focus switched from reconstructive toward regenerative techniques, with emerging options including cell-free and tissue-engineering strategies to restore the cartilage surface. LEVEL OF EVIDENCE: IV.

Bone marrow aspirate concentrate injections provide similar results versus viscosupplementation up to 24 months of follow-up in patients with symptomatic knee osteoarthritis. A randomized controlled trial.

PURPOSE: The purpose of this double-blind randomized controlled trial (RCT) was to compare clinical improvement and radiographic findings up to 2 years of follow-up of a single intra-articular injection of bone marrow aspirate concentrate (BMAC) versus hyaluronic acid (HA) for the treatment of knee osteoarthritis (OA). The hypothesis was that BMAC injection could lead to better clinical and radiographic results compared to viscosupplementation. METHODS: Patients with bilateral knee OA were randomized to one intra-articular injection of tibial-derived BMAC in one knee and one HA injection in the contralateral knee. Sixty patients were enrolled, and 56 were studied up to the final follow-up (35 men, 21 women, mean age 57.8 ± 8.9 years), for a total of 112 knees. Patients were evaluated before the injection and at 1, 3, 6, 12, and 24 months with the IKDC subjective score, VAS for pain, and the KOOS score. Minimal clinically important difference (MCID), patient treatment judgement, and adverse events were documented, as well as bilateral X-Rays (Rosenberg view) before and after treatment. RESULTS: No severe adverse events nor differences were reported in terms of mild adverse events (7.1% vs 5.4%, p = ns) and treatment failures (10.7% vs 12.5%, p = ns) in BMAC and HA groups, respectively. The IKDC subjective score improved from baseline to all follow-ups for BMAC (p < 0.0005), while it improved up to 12 months (p < 0.0005) and then decreased at 24 months (p = 0.030) for HA. Compared to HA, BMAC showed a higher improvement for VAS pain at 12 (2.2 ± 2.6 vs 1.7 ± 2.5, p = 0.041) and 24 months (2.2 ± 2.6 vs 1.4 ± 2.8, p = 0.002). The analysis based on OA severity confirmed this difference only in Kellgren-Lawrence 1-2 knees, while comparable results were observed in moderate/severe OA. Radiographic evaluation did not show knee OA deterioration for both treatment groups, without intergroup differences. CONCLUSION: BMAC did not demonstrate a clinically significant superiority at short-term compared to viscosupplementation, reporting overall comparable results in terms of clinical scores, failures, adverse events, radiographic evaluation, MCID achievement, and patient treatment judgment. However, while HA results decreased over time, BMAC presented more durable results in mild OA knees. LEVEL OF EVIDENCE: Level I.

Matrix-assisted chondrocyte transplantation with bone grafting for knee osteochondritis dissecans: stable results at 12 years.

PURPOSE: To document clinical and radiological results of arthroscopic matrix-assisted autologous chondrocyte transplantation (MACT) combined with bone grafting for the treatment of knee osteochondritis dissecans (OCD) at long-term follow-up. METHODS: Thirty-one knees in 29 patients (20.4 ± 5.7 years) were treated for symptomatic unfixable OCD lesions (2.6 ± 1.1 cm2) and prospectively evaluated at 2, 5, and 12 years (average, minimum 10 years). Patients were evaluated over time with IKDC subjective score, EQ-VAS, and Tegner scores. Failures were also documented. At the final follow-up, MRI evaluation was performed in 14 knees with the MOCART 2.0 score. RESULTS: Beside 4 early failures, an overall clinical improvement was documented: the IKDC subjective score improved from 39.9 ± 16.8 to 82.1 ± 17.0 and 84.8 ± 17.2 at 2 and 5 years, respectively (p < 0.0005), and remained stable for up to 12 years (85.0 ± 20.2). EQ-VAS and Tegner scores presented similar trends, but patients did not reach their original activity level. Worse results were obtained for lesions bigger than 4 cm2. At MRI evaluation, subchondral bone abnormalities were detected in over 85% of knees at long-term follow-up. CONCLUSIONS: Arthroscopic bone grafting followed by MACT for unfixable knee OCD can offer a promising and stable clinical outcome over time in lesions smaller than 4 cm2, with a low failure rate of 13%. Persistent subchondral alterations were documented at long-term MRI evaluation, suggesting the limits of this approach to regenerate the osteochondral unit in patients affected by knee OCD. LEVEL OF EVIDENCE: IV.

Subchondral and intra-articular injections of bone marrow concentrate are a safe and effective treatment for knee osteoarthritis: a prospective, multi-center pilot study.

PURPOSE: Subchondral bone is becoming a treatment target for knee OA patients, with promising early findings on the use of bone marrow aspirate concentrate (BMAC). The aim of this prospective, multi-centric pilot study was to evaluate safety as well as clinical and MRI outcomes of a combined approach of intra-articular and subchondral BMAC injections. METHODS: Thirty patients (19 men, 11 women, 56.4 ± 8.1 years) with symptomatic knee OA were treated with a combination of an intra-articular and two subchondral BMAC injections (femoral condyle and tibial plateau). Patients were evaluated at baseline and at 1-3-6-12 months of follow-up with the IKDC subjective, VAS, KOOS, and EQ-VAS scores. The MRI evaluation was performed with the WORMS score. RESULTS: No major complications were reported and only two patients were considered treatment failures, requiring a new injective or surgical treatment. The IKDC subjective score improved significantly from 40.5 ± 12.5 to 59.9 ± 16.1 at 3 months, 59.1 ± 12.2 at 6 months, and 62.6 ± 19.4 at 12 months (p < 0.0005). A similar improvement was reported for VAS pain and all KOOS subscales at all follow-ups, while EQ-VAS did not show any significant improvement. The MRI analysis showed a significant bone marrow edema reduction (p = 0.003), while the remaining WORMS parameters did not show any significant changes. CONCLUSION: The pilot evaluation of this combined BMAC injective treatment showed safety and positive outcome up to 12 months of follow-up in patients with symptomatic knee OA associated with subchondral bone alterations. These findings suggest that targeting both subchondral bone and joint environment can provide promising results, and that BMAC can be a valid option for this combined approach to treat knee OA.

Osteochondral autograft transplantation versus autologous bone-cartilage paste grafting for the treatment of knee osteochondritis dissecans.

PURPOSE: To compare the results of two groups of patients affected by osteochondritis dissecans (OCD) of the knee and treated with either osteochondral autologous transplantation (OAT) or bone-cartilage paste grafting (PG). METHODS: A total of 27 patients affected by OCD lesions of the femoral condyles were included: 15 treated with OAT, 12 with PG, with comparable baseline characteristics (mean age 22.4 ± 7.2 vs. 24.2 ± 8.5 p = n.s., mean defect size 2.2 ± 1 cm2 vs 2.6 ± 1 cm2 p = n.s.). Patients were evaluated pre-operatively and at 24 and 84 months post-operatively with the International Knee Documentation Committee (IKDC) subjective and objective scores. Sport activity level was evaluated with the Tegner activity score. Adverse events and failures were also recorded. RESULTS: The IKDC subjective score improved significantly in both groups. At 24 months, a significant improvement from 53.4 ± 9.1 to 80.8 ± 12.9 (p = 0.005) was obtained in the OAT group and from 44.6 ± 11.0 to 71.4 ± 25.3 in the PG group (p = 0.008). A further statistically significant increase was observed at 84 months in both groups. No significant differences were found between OAT and PG at both follow-ups. One OAT patient required post-operative knee mobilization under narcosis and two complained of donor site symptoms. More failures were documented in the PG vs OAT group (25% vs 0%; p = 0.043). CONCLUSION: Both PG and OAT provided overall satisfactory results up to 84 months follow-up. However, while PG presents the advantages of a less invasive approach with lower adverse events, the higher failure rate of PG should be considered when choosing between these two surgical treatment options for restoration of the articular surface in patients affected by knee OCD.

Non-Coding RNAs in the Transcriptional Network That Differentiates Skeletal Muscles of Sedentary from Long-Term Endurance- and Resistance-Trained Elderly.

In a previous study, the whole transcriptome of the vastus lateralis muscle from sedentary elderly and from age-matched athletes with an exceptional record of high-intensity, life-long exercise training was compared-the two groups representing the two extremes on a physical activity scale. Exercise training enabled the skeletal muscle to counteract age-related sarcopenia by inducing a wide range of adaptations, sustained by the expression of protein-coding genes involved in energy handling, proteostasis, cytoskeletal organization, inflammation control, and cellular senescence. Building on the previous study, we examined here the network of non-coding RNAs participating in the orchestration of gene expression and identified differentially expressed micro- and long-non-coding RNAs and some of their possible targets and roles. Unsupervised hierarchical clustering analyses of all non-coding RNAs were able to discriminate between sedentary and trained individuals, regardless of the exercise typology. Validated targets of differentially expressed miRNA were grouped by KEGG analysis, which pointed to functional areas involved in cell cycle, cytoskeletal control, longevity, and many signaling pathways, including AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), which had been shown to be pivotal in the modulation of the effects of high-intensity, life-long exercise training. The analysis of differentially expressed long-non-coding RNAs identified transcriptional networks, involving lncRNAs, miRNAs and mRNAs, affecting processes in line with the beneficial role of exercise training.

Long-term Results of Matrix-assisted Autologous Chondrocyte Transplantation Combined With Autologous Bone Grafting for the Treatment of Juvenile Osteochondritis Dissecans.

BACKGROUND: Osteochondritis dissecans is a pathology affecting young patients that involves the entire osteochondral unit. In the case of unfixable fragments, regenerative cartilage treatments are a viable solution, but little is known about the use of these procedures for the treatment of juvenile osteochondritis dissecans (JOCD). The aim of this study was to evaluate the long-term results offered by matrix-assisted autologous chondrocyte transplantation combined with autologous bone grafting for the treatment of JOCD. METHODS: Nineteen patients have been enrolled. The mean age at the time of treatment was 16.8±1.5 years, with a mean body mass index of 22.9±2.7. The average size of the defects was 2.8±1.2 cm. All patients were evaluated prospectively before surgery and at 12, 24, 60, and at a final follow-up of 120 months with International Knee Documentation Committee scores, EuroQol-Visual Analogue Scale, and the Tegner Score. RESULTS: A statistically significant improvement in all clinical scores was observed from baseline evaluation to 120 months of final follow-up. In particular, the International Knee Documentation Committee subjective score improved from the preoperative evaluation of 38.7±17.3 to 74.0±21.8 at 12 months (P<0.0005), with scores remaining stable for up to 120 months (83.8±20.7), with all follow-ups showing a statistically significant improvement compared with the basal value (P<0.0005). Three patients failed at 12 months, for a failure rate of 16% at 10 years of follow-up. Lesions >3.5 cm obtained worse subjective results. In addition, lesion size and female sex were significantly associated with failures. CONCLUSIONS: The matrix-assisted autologous chondrocyte transplantation technique with autologous bone grafting is a valid treatment option for JOCD in case of unfixable fragments. The clinical improvement obtained is significant and stable, with good results maintained for up to 10 years of follow-up and an overall low failure rate. Lesion size and sex could influence the clinical outcome and should be considered in the treatment choice. LEVEL OF EVIDENCE: Level IV-case series.

Skeletal Muscle Gene Expression in Long-Term Endurance and Resistance Trained Elderly.

Physical exercise is deemed the most efficient way of counteracting the age-related decline of skeletal muscle. Here we report a transcriptional study by next-generation sequencing of vastus lateralis biopsies from elderly with a life-long high-level training practice (n = 9) and from age-matched sedentary subjects (n = 5). Unsupervised mixture distribution analysis was able to correctly categorize trained and untrained subjects, whereas it failed to discriminate between individuals who underwent a prevalent endurance (n = 5) or a prevalent resistance (n = 4) training, thus showing that the training mode was not relevant for sarcopenia prevention. KEGG analysis of transcripts showed that physical exercise affected a high number of metabolic and signaling pathways, in particular those related to energy handling and mitochondrial biogenesis, where AMPK and AKT-mTOR signaling pathways are both active and balance each other, concurring to the establishment of an insulin-sensitive phenotype and to the maintenance of a functional muscle mass. Other pathways affected by exercise training increased the efficiency of the proteostatic mechanisms, consolidated the cytoskeletal organization, lowered the inflammation level, and contrasted cellular senescence. This study on extraordinary individuals who trained at high level for at least thirty years suggests that aging processes and exercise training travel the same paths in the opposite direction.

A Composite Chitosan-Reinforced Scaffold Fails to Provide Osteochondral Regeneration.

Several biomaterials have recently been developed to address the challenge of osteochondral regeneration. Among these, chitosan holds promises both for cartilage and bone healing. The aim of this in vivo study was to evaluate the regeneration potential of a novel hybrid magnesium-doped hydroxyapatite (MgHA), collagen, chitosan-based scaffold, which was tested in a sheep model to ascertain its osteochondral regenerative potential, and in a rabbit model to further evaluate its ability to regenerate bone tissue. Macroscopic, microtomography, histology, histomorphometry, and immunohistochemical analysis were performed. In the sheep model, all analyses did not show significant differences compared to untreated defects (p > 0.05), with no evidence of cartilage and subchondral bone regeneration. In the rabbit model, this bone scaffold provided less ability to enhance tissue healing compared with a commercial bone scaffold. Moreover, persistence of scaffold material and absence of integration with connective tissue around the scaffolds were observed. These results raised some concerns about the osteochondral use of this chitosan composite scaffold, especially for the bone layer. Further studies are needed to explore the best formulation of chitosan-reinforced composites for osteochondral treatment.

Anterior cruciate ligament injury: post-traumatic bone marrow oedema correlates with long-term prognosis.

PURPOSE: Bone marrow oedema (BME) in the knee is a feature of several pathological conditions, and it has been described with high frequency in patients with acute anterior cruciate ligament (ACL) injury. The aim of this study is to evaluate the significance of BME, assessed in MRIs performed for ACL injury, with regards to clinical outcome and return to sport. METHODS: A total of 134 patients (98 men, 36 women) with ACL tear and MRI knee scan within six months from trauma were analysed. The presence of BME was evaluated on MRI images considering: extension and hyperintensity, the WORMS score oedema classification, and measuring the BME area. The clinical results were documented by IKDC-subjective score and the sport activity level by Tegner score at a minimum of five years follow up. RESULTS: BME was present in 74 knees (55.2 %), with a mean area of 523 ± 370 mm². The presence of BME showed a gradual decrease over time (p = 0.008), being detectable in MRIs performed more than three months after trauma in just 25.0 % of cases. Although 54 % of the patients without BME after three months returned to their previous sport level, no patients with oedema reached a full sport recovery (p = 0.01). In the group that underwent ACL reconstruction, the BME area was significantly correlated with a return to the previous sport level at the mid/long-term follow-up (p = 0.038). CONCLUSIONS: BME is a common finding, which decreases over time after injury. However, when BME is still detectable it correlates with clinical prognosis, and even in sport-active patients undergoing ACL reconstruction, a higher BME area is a negative predictive factor for a successful outcome at the mid/long-term follow-up.

A one-step treatment for chondral and osteochondral knee defects: clinical results of a biomimetic scaffold implantation at 2 years of follow-up.

The increasing interest in the role of subchondral bone with regard to articular surface disease led to the development of new bioengineered strategies. Aim of this study is to evaluate the clinical and MRI outcome after the implantation of a nanostructured biomimetic three-phasic collagen-hydroxyapatite construct for the treatment of chondral and osteochondral defects of the knee in a large cohort of patients. Seventy-nine patients (63 M, 16 W), affected by grade III-IV femoral condyle or trochlea chondral lesions or osteochondritis dissecans (OCD) were consecutively treated. Mean age was 31.0 ± 11.3 years, mean lesion size was 3.2 ± 2.0 cm(2). Fifty patients underwent previous surgeries, concurrent procedures were necessary in 39 cases. The clinical outcome was evaluated using the IKDC and Tegner scores at 12 and 24 months of follow-up. At follow-up times an MRI was performed and evaluated with the MOCART score. All the scores improved significantly from the baseline. IKDC subjective score showed a further increase between 12 and 24 months of follow-up, and 82.2% of the patients improved their symptoms at the final evaluation. Patients affected by OCDs had better results than those with degenerative lesions. Some abnormal MRI findings were present, even though no correlation was found with the clinical outcome. This one-step biomimetic approach developed to favor osteochondral tissue regeneration is effective in treating knees affected by damages of the articular surface, leading to a significant clinical improvement. However, abnormal MRI findings were present, even if not correlated with the clinical outcome.

Is the clinical outcome after cartilage treatment affected by subchondral bone edema?

PURPOSE: Subchondral bone edema is a common finding after cartilage treatment, but its interpretation is still debated. The aim of this study is to analyse the presence of edema after matrix-assisted autologous chondrocyte transplantation (MACT) for knee cartilage lesions at different follow-up times and its correlation with the clinical outcome. METHODS: Two hundred and forty-eight magnetic resonance imagings (MRIs) of patients treated with a hyaluronic acid-based MACT for lesions of the knee articular surface were considered. The MRIs belonged to 116 patients (mean age at surgery 28.6 ± 10.3 years, average defect size 2.4 ± 1.0 cm(2)), 57 affected by degenerative cartilage lesions, 27 traumatic and 32 were osteochondritis dissecans (OCD). MRI follow-up was performed from 6 to 108 months after treatment. Other than its presence or absence, the subchondral bone edema was evaluated using a 3-level grading considering extension and hyperintensity, and with the WORMS score edema classification. The IKDC subjective score was collected at the time of every MRI. RESULTS: An analysis of the entire MRI group showed that edema is not constantly present through the follow-up, but presents a particular and well-defined trend. Edema was present within the first 2 years and was then markedly reduced or disappeared at 2 and 3 years (p = 0.044). Afterwards the level of edema increased again (p < 0.0005) and remained steadily present at medium/long-term follow-up. Patellar lesions presented significantly lower edema (p = 0.012), whereas OCD lesions presented more edema at all follow-up (p = 0.002) and a different trend, with an increasing level of edema over time. No correlation was found between edema and clinical outcome. CONCLUSIONS: Edema after MACT is present during the first phases of cartilage maturation up to 2 years of follow-up, and then tends to disappear. However, after a few years, it tends to reappear. Less edema was found in the patella, whereas more edema was found in the OCD, where subchondral bone is primarily involved. Interestingly, the presence of edema was not correlated with a poorer clinical outcome. Whether this might be a prognostic factor at longer follow-up remains to be determined, but our results give some indication on what to expect on both MRI edema and clinical outcome after MACT. LEVEL OF EVIDENCE: Case series, Level IV.

Biodegradable polyurethane meniscal scaffold for isolated partial lesions or as combined procedure for knees with multiple comorbidities: clinical results at 2 years.

PURPOSE: The aim of this study is to evaluate the safety and clinical efficacy of this novel polyurethane meniscal scaffold to treat partial meniscal loss. METHODS: Eighteen patients (11 men and 7 women, mean age: 45 years) affected by irreparable acute meniscal tears requiring partial meniscectomy or chronic prior loss of meniscal tissue were enrolled in the study. They underwent arthroscopic polyurethane meniscal scaffold implantation (13 medial and 5 lateral) and, in case of presence of other comorbidities, concurrent procedures were also performed. Patients were prospectively evaluated up to 2 years of follow-up through IKDC objective, IKDC subjective, and Tegner scores. Furthermore, MRI evaluation of the meniscal scaffold was performed. RESULTS: No major adverse events were observed. A statistically significant increase in all the clinical parameters considered was found. The IKDC objective score increased from 61 % of normal or nearly normal knees at basal evaluation to 94 % at 2 years of follow-up (p = 0.01). There was also a significant increase in the IKDC subjective score both at 6-12 months of follow-up (p = 0.03 and p < 0.005), which was confirmed at 24 months. The Tegner score also showed a significant increase from the pre-operative level (median value 2, range 1-5) to final evaluation (median value 3, range 2-5; p = 0.005), albeit not reaching the pre-injury sports activity level. CONCLUSIONS: The implantation of this novel polyurethane scaffold proved to be a safe and potentially effective procedure to treat partial meniscal loss with encouraging results at short-term follow-up. Further high-quality studies with larger numbers of patients and longer evaluation times are needed to confirm these preliminary data.