Mechanisms of treatment effects using allogeneic, umbilical cord-derived mesenchymal stromal stem cells (MSCs) in knee osteoarthritis: a pharmacological clinical study protocol.

BACKGROUND: Knee osteoarthritis (KOA) presents a prevalent orthopedic condition causing substantial impairment in the quality of life and imposing a significant societal and economic burden. Mesenchymal stromal/stem cells (MSCs), known for their regenerative properties and immunomodulatory effects, have emerged as a promising therapeutic avenue in regenerative medicine. Despite MSCs' therapeutic potential, their precise mechanisms of action in KOA remain underexplored. METHODS: Conducted as a randomized, open-label clinical trial, 20 patients will be enrolled, with 10 in the intervention group and 10 in the control group. The primary focus will be to explore the molecular mechanisms associated with MSC therapy. Biomarkers and gene expressions related to cartilage metabolism, inflammation, immune modulation, and pain in the synovial fluid, blood, and tissue samples will be analyzed. Patients will undergo pre- and post-treatment evaluations using patient-reported outcome measures (PROMs) and comprehensive clinical assessments. DISCUSSION: This is an exploratory study with the goal to provide comprehensive insights into the therapeutic effects of MSCs on a molecular level, potentially paving the way for optimized and more effective MSC-based therapies in the management of KOA, as well as furthering the development of novel treatment strategies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT06078059. Registered on 5 October 2023.

A Biomimetic Osteochondral Scaffold Augmented With Filtered Bone Marrow Aspirate for the Treatment of Joint Surface Lesions in the Knee.

BACKGROUND: Multilayered osteochondral scaffolds are becoming increasingly utilized for the repair of knee joint surface lesions (KJSLs). However, the literature on predictive factors is rather limited. PURPOSE: To (1) evaluate the clinical outcomes and safety of a combined single-step approach using a biomimetic collagen-hydroxyapatite scaffold (CHAS) and filtered bone marrow aspirate (fBMA) for the treatment of KJSLs and (2) identify significant predictors of the treatment outcomes. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: All patients who underwent surgery because of a KJSL (size ≥1.5 cm2; International Cartilage Regeneration & Joint Preservation Society grades 3-4) using the combination above were selected from a hospital registry database (100 patients; minimum 2-year follow-up). Patient characteristics, medical history, knee joint and lesion status, intraoperative details, and cellular parameters of the injected fBMA were collected. The arthroscopic evaluation of chondral and meniscal tissue quality in all knee compartments was performed using the Chondropenia Severity Score. Treatment outcomes were determined clinically using patient-reported outcome measures (Knee Injury and Osteoarthritis Outcome Score, EuroQol-5 Dimensions-3 Levels, EuroQol-Visual Analog Scale, and Tegner Activity Scale) and by assessing the occurrence of serious adverse events and graft failure. Multivariable regression analysis was performed to identify significant predictors of the treatment outcomes. RESULTS: At a mean follow-up of 54.2 ± 19.4 months, 78 (87%) patients completed the questionnaires with significant improvements toward the baseline (P < .00625): KOOS Pain subscale from 62 ± 17 to 79 ± 18, KOOS Total score from 57 ± 16 to 70 ± 20, EuroQol-Visual Analog Scale from 61 ± 21 to 76 ± 16, EuroQol-5 Dimensions-3 Levels from 0.57 ± 0.20 to 0.80 ± 0.21, and Tegner Activity Scale from 2.8 ± 1.5 to 3.9 ± 1.9. The graft failure rate was 4%. A longer duration of preoperative symptoms, previous surgery, larger lesions, older age, and female sex were the main negative predictors for the treatment outcomes. The Chondropenia Severity Score and the number of fibroblast colony-forming units in fBMA positively influenced some of the clinical results and safety. CONCLUSION: A CHAS augmented with fBMA proved to be an adequate and safe approach for the treatment of KJSLs up to midterm follow-up. Based on the subanalysis of predictive factors, the surgical intervention should be performed in a timely and precise manner to prevent lesion enlargement, deterioration of the general knee cartilage status, and recurrent surgical procedures, especially in older and female patients. When a CHAS is used, the quantity of MSCs seems to play a role in augmentation. REGISTRATION: NCT06078072 (ClinicalTrials.gov identifier).

The Coronal Alignment of Lower Limbs in the Adolescent Football and Ice Hockey Players.

Background: To investigate the influence of sport-specific activities on coronal axial alignment of the lower limbs in adolescent football and ice hockey players. Methods: This cross-sectional study targeted healthy adolescent male football and ice hockey players with at least 3 years of sports participation. 90 football and 38 ice hockey players aged 12-16 years were divided into five age-matched subgroups. Coronal alignment of the lower limbs was determined by measuring the players' intercondylar or intermalleolar (ICD-IMD) distance with a custom-made calliper. In addition, their sports history was recorded. An age-matched comparison between the two sports groups was performed using the two-way model ANOVA and a multiple regression model for ICD-IMD was constructed. Results were additionally compared with age-matched data from the general population published in recent literature. Results: A statistically significant increase in ICD-IMD values (p < 0.05) was found between 12 (football 0 mm; ice hockey - 64 mm) and 16 years (football 340 mm; ice hockey 310 mm) in both sports groups. Results of regression analysis of pooled group data showed that ICD-IMD has low positive correlation (r = 0.407; r2 = 0.168; p < 0.05) with time of participation in sport, but no association with age of athletes at the start of their sport participation (r = - 0.018; r2 = 0.000; p > 0.05). There were no statistically significant differences between the two groups at any time point. Both sports groups showed a significant increase in ICD-IMD values (mean 198 mm) after the age of 14 compared to the general population. Conclusions: Participation in football and ice hockey is associated with a similar increase in ICD-IMD in the adolescent years in male athletes. The observed increase was higher in both groups of athletes than in their peers who do not regularly participate in sports. Level of Evidence: Level 4 (case series).

Biomaterials augmented with filtered bone marrow aspirate for the treatment of talar osteochondral lesions. A comparison of clinical and cellular parameters.

BACKGROUND: Biomaterials augmented with Bone Marrow Aspirate Concentrate (BMAC) are becoming increasingly utilized in the cartilage treatment. However, the potential role of cellular parameters in the intraoperatively applied BMAC have yet to be elucidated. PURPOSE: (A) To evaluate clinical outcomes and safety of a combined single-step approach with scaffolds (fibrin glues, collagen gels, collagen-hydroxyapatite membrane) and filtered Bone Marrow Aspirate (fBMA) for the treatment of osteochondral lesions of the talus (OLTs). (B) To identify significant factors for postoperative improvements, considering cellular parameters as potential predictors. METHODS: All the patients operated on due to OLTs by the combination above were selected from the hospital registry database (35 pts, years 16-55, and minimally 1 year follow-up). Treatment outcomes were followed clinically with Patient-reported outcome measures (PROMs), and by pursuing serious adverse events (SAE) and graft failures (GF). Cellular parameters of the injected fBMA were determined. Pre- and postoperative PROMs values were compared to evaluate postoperative improvements. Multivariable regression models were applied to identify potential factors (demographics, medical history, joint and lesion characteristics, scaffold type, surgical and cellular parameters) that predict the treatment outcomes. RESULTS: At the mean follow-up of 32.2 (12.5) months, all Foot and Ankle Outcome Score (FAOS) and European Quality of Life in Five Dimensions Three-Level (EQ-5D-3 L) values improved significantly. 4 (11%) SAE (3 arthrofibrosis, one hardware removal), and 3 (9%) GF occurred. Female gender and concomitant procedures were the main negative predictors for postoperative outcomes. The number of fibroblast colony forming units (CFU-F) or their proportion among total nucleated cells (CFU-F/TNC) were positively correlated with the improvements of some PROMs. CONCLUSIONS: Scaffolds augmented with fBMA proved as an adequate and safe approach for OLTs treatment. Cellular parameters seem to influence the treatment outcomes, thus further attention should be given to the intraoperatively applied products. LEVEL OF EVIDENCE: Level IV.

Partial Ankle Arthroplasty: Talus Resurfacing for Mild to Moderate Osteoarthritis and Talus Hemiarthroplasty for Complex Osteochondral Lesions.

BACKGROUND: To present prospective short-term results of a limited patient series treated with two innovative partial ankle arthroplasties: talar dome resurfacing for mild-to-moderate ankle osteoarthritis (OA) and talar shoulder hemiarthroplasty for chronic medial osteochondral lesions of the talus (OLT). METHODS: Eleven subjects underwent talus resurfacing, and six subjects were enrolled for talar hemiarthroplasty. The outcome was followed by patient-reported measures and by pursuing serious adverse events or implant failures over a 2-year period. Progression of ankle osteoarthritis, peri-implant bone changes, and implant migration were followed radiographically. RESULTS: Active dorsiflexion increased from 3° to 10° in resurfacing and from 15° to 22° in hemiarthroplasty. Patient-reported ankle function, quality of life, and activity level tended to improve only slightly after resurfacing (FAOS cumulative = 41 to 42; FAAM-ADL = 43 to 46; EQ-5D 3L = 0.38 to 0.39, Tegner activity scale = 1.6 to 2.0), but moderately after hemiarthroplasty (FAOS cumulative = 58 to 68, FAAM-ADL = 37 to 71, EQ-5D 3L = 0.53 to 0.72, Tegner activity scale = 3.1 to 3.1). No implant-related radiographic changes, implant failures, or implant-related revision surgeries were recorded. CONCLUSIONS: Based on a small and heterogeneous prospective case series, both partial ankle implants investigated were safe and stable over a 2-year follow-up period, without any radiographic OA progression of the remaining joint. However, patient-reported ankle function, quality of life, and activity level showed a tendency of only minor improvement after resurfacing but a moderate increase after hemiarthroplasty.

Knee osteoarthritis in the former elite football players and the ordinary population: a comparative cross-sectional study.

A cross-sectional case-control study compared subjective knee function, quality of life and radiographic knee osteoarthritis (OA) between 45 former elite football players and an age-matched general male population. Participants completed the Knee OA Outcome Score (KOOS), a quality-of-life assessment (EQ-5D-3 L) and standing knee radiographs. Among the players, 24 (53%) sustained at least one moderate or severe knee injury, while 21 (47%) did not recall any injury. Players with previous knee injuries reported significantly lower knee-specific and general quality-of-life scores (KOOS 69; EQ-5D-3 L 0.69 (0.2)) compared to the non-injured players (KOOS 92; EQ-5D-3 L 0.81 (0.2)) or the control population (KOOS 90; EQ-5D-3 L 0.83 (0.2)). The injured knees had higher radiographic OA Kellgren-Lawrence (KL) scale grades 1.7 (1.3) than the knees of the non-injured players 0.8 (1.0) or the control knees 0.8 (1.0)Former elite football players who had previously sustained a moderate or severe knee injury reported inferior knee function and lower quality of life. Injured knees had higher levels of radiographic OA. Non-injured players reported similar knee and general function and their knees had similar grades of OA to those in the control group. The defining moment for long-term knee preservation in football should be injury prevention protocols.

Multilayered biomimetic scaffolds for cartilage repair of the talus. A systematic review of the literature.

OBJECTIVE: The aim of the present review was to analyze the available evidence in the literature on the clinical and radiological outcomes of multilayered biomimetic scaffolds in the treatment of osteochondral lesions of the talus (OLTs). DESIGN: A systematic search was performed in three databases to identify clinical trials, where the multilayered biomimetic scaffolds were used for the treatment of OLTs. The PRISMA guidelines were followed. Qualitative analysis of the relevant data of the included studies was executed. The methodological quality of the analyzed studies was assessed with a modified Coleman Methodology Score (CMS). RESULTS: A total of 10 studies with 87 patients were included in the analysis. Only three multilayered biomimetic scaffolds have been investigated in clinical trials for the treatment of OLTs. The worst clinical and radiological outcomes, as well as safety profile were observed for the TruFit scaffold (Smith & Nephew, Andover, MA, USA), which had already been withdrawn from the market. The other two scaffolds (MaioRegen, Finceramica, Italy; Agili-C, Cartiheal, Israel) performed significantly better in the majority of the reviewed studies, especially in the clinical aspect. The radiological findings, the improvements of MOCART scores, the completeness of lesions' fill, and the structure of regenerated tissue were much more inconsistent. CONCLUSIONS: Two of the multilayered biomimetic scaffolds demonstrated an adequate potential in the treatment of complex OLTs. However, limited studies availability and their low level of medical evidence request further high-level investigations before the clinical decision making for such scaffolds in the treatment of OLTs can be defined.

Age, body mass index, female gender, and patellofemoral cartilage degeneration predict worse patient outcome after patellofemoral instability surgery.

PURPOSE: To evaluate predicting factors for patient-reported outcomes and revision interventions following surgical treatment of patients with patellofemoral instability. METHODS: From a prospective database at the university Orthopedic Department, 138 knees from 116 patients who underwent patellofemoral instability surgery (2012-2019) were enrolled in a retrospective analysis: 34 cases of isolated MPFLrec; 92 cases of MPFLrec plus tibial tuberosity transfer; and 12 cases of MPFLrec plus trochleoplasty. Patient-reported outcome measures were recorded for knee-specific function (KOOS), general quality of life (EQ-5D), and activity level (Tegner scale). Post-operative revision interventions were also actively recorded. As potential predicting factors, patient demographic (gender, age, BMI) and radiographic (pre-operative: patellar height and tilt, tibial tuberosity-trochlear groove distance, trochlear dysplasia, knee osteoarthritis; post-operative: MPFL insertion point; intra-operative: isolated vs. combined procedures, chondropenia severity score) parameters were analyzed using multivariate linear regression models. RESULTS: With median follow-up of 4.4 (1.0-8.9) years, all patient-reported outcome measures had significantly improved from pre-operative levels: KOOS cumulative, from 71 (15) to 78 (16); EQ-5D, from 0.68 (0.20) to 0.78 (0.21); and Tegner activity scale, from 3 (0-10) to 4 (0-10). No patellofemoral instability revision procedures were performed. One-fifth (27/138) of the operated knees required second surgical interventions, predominately due to hardware or arthrofibrosis. Patients who required post-operative knee manipulation under anesthesia or arthroscopic debridement showed lower post-operative improvement for KOOS cumulative and EQ-5D. Age, BMI, patellofemoral knee osteoarthritis, and shorter follow-up time revealed significant negative correlations to some of the post-operative KOOS subscales. Age was negatively correlated to post-operative EQ-5D, while post-operative Tegner activity scale was negatively correlated to female gender and patellofemoral chondropenia severity score. Femoral MPFL insertion point revealed no association with any outcome measures. CONCLUSION: Patellofemoral instability surgery for isolated or combined MPFLrec is safe and substantially improves knee function and patient quality of life and activity levels. Serious adverse events are rare, with no recurrent patellofemoral instability. Patients who required post-operative knee manipulation or arthroscopic debridement showed less improvement in subjective measures of treatment outcomes. Older age, higher BMI, worse pre-operative patellofemoral cartilage status, and female gender had negative effects on outcome. LEVEL OF EVIDENCE: III.

Patient Outcomes Following Extra-Osseous Talo-Tarsal Stabilization for Foot Hyperpronation.

The aim is to present a single-center case series of patients with symptomatic hyperpronated feet treated with arthroereisis by using a second generation extra-osseous talo-tarsal stabilization device. This case series enrolled 123 feet in 87 patients (20 [6-75] years) treated with arthroereisis, either isolated (76 cases) or combined procedure (47 cases). At their final follow-up, a patient reported questionnaire (overall satisfaction, foot stability and shape, activities of daily living, pain level, and analgesics usage) was distributed. The average postoperative follow-up period was 30 (13-55) months. Nineteen (15%) cases required at least one revision surgery: the implant was manipulated in 5 (4%), while 14 cases (11%) required definitive implant removal. The predominant reason for implant removal was pain (50%), followed by implant migration (27%). The pediatric population with isolated procedure showed lowest revision rate (5%), while adults with combined ankle/hindfoot procedures demonstrated revision rate of 50%. The overall patient satisfaction after arthroereisis was 84%. The patients' perceived improvement in foot stability was 75%, foot shape 85%, and activities of daily living 64%. Eighty-two percent of cases reported no analgesics usage in the last month and mean visual analogue scale (0-10) pain level decreased from 5.5 to 2.2 (p < .001). The subgroup analyses of patient-reported questionnaires revealed the best outcome in the pediatric-isolated cases, while adults with combined procedures reported the lowermost outcome. Extra-osseous talo-tarsal stabilization demonstrated a low rate of revisions surgery and a high satisfaction rate as an isolated procedure. Patients with conjoined procedures experienced more revisions and considerably lower satisfaction rates.

A prospective, single-center study following operative treatment for osteochondral lesions of the talus.

BACKGROUND: (1) To evaluate patient-reported outcomes and revision surgeries after various operative interventions for osteochondral lesions of the talus (OLT) in a prospective single center series over 10 years, and (2) to identify predicting factors related to subjective ankle status and quality of life pre- and postoperatively. METHODS: Ninety-nine patients underwent operative treatment due to primary or recurrent OLT, with an average follow up 3.5 (1.8) years. Treatment outcome was followed clinically (FAOS, EQ-5D, Tegner activity scale) and by pursuing any serious adverse events or graft failures. RESULTS: There were 80 responding patients (81%) for the study. The mean lesion size was 2.0 (1.1) cm2. All FAOS values increased from preoperative to final follow-up values (Symptoms 60-68, Pain 58-69, ADL 71-80, Sport 36-54, QoL 30-45). EQ-5D increased from 0.49 to 0.62, while Tegner activity scale change from 3.2 to 3.4. There were 19 (24%) serious adverse events recorded; 13 (16%) of them were graft-related. Graft survival rates were 100% at 1 year, 94% (males)/93% (females) at 2 years, and 77% (males)/47% (females) at 5 years. Female gender, higher BMI, and higher Kellgren-Lawrence ankle OA score were negative predictors for preoperative patient-reported ankle joint status. The foremost improvement after operative intervention was observed in patients with large osteochondral lesions without postoperative adverse events. CONCLUSION: Various operative interventions for OLT significantly improved patients' ankle status and quality of life. High graft survival rates were demonstrated over first two years, but notable decline was confirmed thereafter, especially in female patients.

Acute Cartilage Injury Induced by Trans-Articular Sutures.

OBJECTIVE: To determine the extent of acute cartilage injury by using trans-articular sutures. METHODS: Five different absorbable sutures, monofilament polydioxanone (PDS) and braided polyglactin (Vicryl), were compared on viable human osteochondral explants. An atraumatic needle with 30 cm of thread was advanced through the cartilage with the final thread left in the tissue. A representative 300 µm transversal slice from the cartilage midportion was stained with Live/Dead probes, scanned under the confocal laser microscope, and analyzed for the diameters of (a) central "Black zone" without any cells, representing in situ thread thickness and (b) "Green zone," including the closest Live cells, representing the maximum injury to the tissue. The exact diameters of suture needles and threads were separately measured under an optical microscope. RESULTS: The diameters of the Black (from 144 to 219 µm) and the Green zones (from 282 to 487 µm) varied between the different sutures (P < 0.001). The Green/Black zone ratio remained relatively constant (from 1.9 to 2.2; P = 0.767). A positive correlation between thread diameters and PDS suturing material, toward the Black and Green zone, was established, but needle diameters did not reveal any influence on the zones. CONCLUSIONS: The width of acute cartilage injury induced by the trans-articular sutures is about twice the thread thickness inside of the tissue. Less compressible monofilament PDS induced wider tissue injury in comparison to a softer braided Vicryl. Needle diameter did not correlate to the extent of acute cartilage injury.

Functional and molecular adaptations of quadriceps and hamstring muscles to blood flow restricted training in patients with ACL rupture.

Effects of low-load blood flow restricted (LL-BFR) training remain unexplored in patients with ACL rupture. Our hypothesis was that LL-BFR training triggers augmented gains in knee muscle strength and size, which are paralleled with transcriptional responses of hypoxia-regulated genes and myokines. Eighteen volunteers (age 37.5 ± 9 years) planned for ACL reconstruction, participated in the study. Twelve were divided between BFR group, performing 9 sessions of LL-BFR exercise, and SHAM-BFR group performing equal training with sham vascular occlusion. Six subjects served as a control for muscle biopsy analysis. Cross-sectional area (CSA) and isokinetic strength of knee muscles were assessed before and after the training. Change in CSAquad was significantly (p < 0.01) larger in BFR (4.9%) compared with SHAM-BFR (1.3%). Similarly, change in peak torque of knee extensors was significantly (p < 0.05) larger in BFR (14%) compared with SHAM-BFR (-1%). The decrease in fatigue index of knee extensors (6%) was larger (p < 0.01) in BFR than in SHAM-BFR (2%). mRNA expression of HIF-1α in the vastus lateralis was reduced (p < 0.05) in SHAM-BFR, while VEGF-A mRNA tended to be higher in BFR. The mRNA expression of myostatin and its receptor were reduced (p < 0.05) in the semitendinosus after both types of training. Expression of IL-6, its receptors IL-6Rα and gp130, as well as musclin were similar in control and training groups. In conclusion, our results show augmented strength and endurance of knee extensors but less of the flexors. LL-BFR training is especially effective for conditioning of knee extensors in this population.

Aragonite-Based Scaffold for the Treatment of Joint Surface Lesions in Mild to Moderate Osteoarthritic Knees: Results of a 2-Year Multicenter Prospective Study.

BACKGROUND: Osteoarthritis (OA) is considered a contraindication to most cartilage repair techniques. Several regenerative approaches have been attempted with the aim of delaying or preventing joint replacement, with controversial results. Currently, there is a paucity of data on the use of single-step techniques, such as cell-free biomimetic scaffolds, for the treatment of joint surface lesions (JSLs) in OA knees. PURPOSE: To present the 2-year follow-up clinical and radiological outcomes after implantation of a novel, cell-free aragonite-based scaffold for the treatment of JSLs in patients with mild to moderate knee OA in a multicenter prospective study. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 86 patients, 60 male and 26 female, with a mean age of 37.4 ± 10.0 years, mild to moderate knee OA, and a mean defect size of 3.0 ± 1.7 cm2, were recruited at 8 medical centers according to the following criteria: radiographic mild to moderate knee OA (Kellgren-Lawrence grade 2 or 3); up to 3 treatable chondral/osteochondral defects (International Cartilage Repair Society grades 3 and 4) on the femoral condyles or trochlea; a total defect size ≤7 cm2; and no concurrent knee instability, severe axial malalignment, or systemic arthropathy. All patients were evaluated at baseline and at 6, 12, 18, and 24 months after implantation using the Knee injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) subjective score. Additionally, magnetic resonance imaging (MRI) was performed to assess the amount of cartilage defect filling at the repaired site. RESULTS: Significant improvement on all KOOS subscales was recorded from baseline (Pain: 49.6 ± 13.1; Activities of Daily Living [ADL]: 56.1 ± 18.4; Sport: 22.8 ± 18.8; Quality of Life [QoL]: 23.5 ± 16.5; Symptoms: 55.4 ± 19.9) to the 24 months' follow-up (Pain: 79.5 ± 21.1 [P < .001]; ADL: 84.1 ± 21.4 [P < .001]; Sport: 60.8 ± 31.9 [P < .001]; QoL: 54.9 ± 30.4 [P < .001]; Symptoms: 77.7 ± 21.2 [P < .001]). The IKDC subjective score showed a similar trend and improved from 37.8 ± 14.7 at baseline to 65.8 ± 23.5 at 24 months (P < .001). MRI showed a significant increase in defect filling over time: up to 78.7% ± 25.3% of surface coverage after 24 months. Treatment failure requiring revision surgery occurred in 8 patients (9.3%). CONCLUSION: The use of an aragonite-based osteochondral scaffold in patients with JSLs and mild to moderate knee OA provided significant clinical improvement at the 24-month follow-up, as reported by the patients. These findings were associated with good cartilage defect filling, as observed on MRI.

The Influence of a Single Intra-Articular Lidocaine Injection on the Viability of Articular Cartilage in the Knee.

OBJECTIVE: To evaluate the in vivo effect of a single intra-articular injection of local anesthetic (LA) lidocaine on the viability of articular cartilage in the intact or osteoarthritic (OA) human knees, and to measure the synovial postinjection concentration of lidocaine in the knee. DESIGN: This study includes 3 interconnected experiments: (A) Synovial LA concentration measurement after a 2% lidocaine injection before knee arthroscopy in 10 patients by liquid chromatography-tandem mass spectrometry (LC-MS/MS). (B) Human osteochondral explants (N = 27) from intact knees procured at autopsies were incubated for different time intervals (30 minutes, 2 hours, 24 hours) with 2% lidocaine, 0.04% lidocaine (measured), or culture medium (control), and later evaluated for cell viability by LIVE/DEAD staining. (C) Ten out of 19 matched patients scheduled for knee replacement received a single intra-articular injection of 2% lidocaine approximately 30 minutes prior to the procedure; 9 patients served as control. Osteochondral samples with OA changes were harvested during surgery and analyzed for chondrocyte viability by LIVE/DEAD staining. RESULTS: (A) The synovial LA concentration was significantly lower than the primary concentration injected: average 0.23 mg/mL (0.02%), highest measured 0.37 mg/mL (0.04%). (B) In vitro exposure to a reduced LA concentration had no significant influence on chondrocyte viability in intact cartilage explants (24-hour averages: control, 93%; 0.04% lidocaine, 92%; 2% lidocaine, 79%). (C) Viability of chondrocytes in OA knees was similar between 2% lidocaine injection (85%) and control (80%). CONCLUSIONS: A single intra-articular knee injection of 2% lidocaine did not influence the chondrocyte viability neither in healthy nor in OA cartilage. A fast postinjection reduction of synovial LA concentration (more than 40 times) is the most likely protective mechanism.

Autologous chondrocytes versus filtered bone marrow mesenchymal stem/stromal cells for knee cartilage repair-a prospective study.

PURPOSE: To document clinical, radiologic, and cellular data of a prospective patient series treated by a tri-layer collagen-hydroxyapatite biomimetic osteochondral scaffold (CHAS) intra-operatively seeded with cultivated autologous chondrocytes (AC) or with filtered bone marrow stem/stromal cells (fBMSC) to address chronic osteochondral knee lesions. METHODS: Thirty-six consecutive patients (15 to 59 years) with chronic osteochondral lesions (1.8-10 cm2) in the condylar or patellofemoral knee surfaces were enrolled. Lesions were covered with CHAS fixed with a fibrin glue. The superficial layer of CHAS was intra-operatively injected with active cells: in initial five patients, ACs were put directly onto dry CHAS (dry-AC); next, eight AC patients had CHAS moistened with cell culture media (media-AC), while the tourniquet was released allowing blood soaking of CHAS in the rest (14 blood-AC, 9 blood-fBMSC). Seventeen (50%) patients required different concomitant procedures. All patients were followed for serious adverse events (SAE) or graft failures; clinical, radiographic, and MRI evaluation was conducted. Cellular data on the injected cells were assessed. RESULTS: At a follow-up of 39 months (16-81), 17 patients required an additional surgical intervention: seven graft-related SAE (early post-operative synovitis and/or arthrofibrosis) were registered (3 dry-AC, 3 media-AC, 1 blood-fBMSC). There were two graft failures (1 dry-AC, 1 blood-fBMSC) for secondary reasons. All clinical scores significantly improved from pre- to post-operative values: IKCD subjective 44 to 65; IKDC examination (9/17/5/5) to (20/10/5/1); KOOS (P61/S59/ADL67/Sp32/QoL31) to (P79/S75/ADL84/Sp55/QoL51); Tegner activity scale 3.3 to 4.4. There was evidence of radiographic osteoarthritis progression-Kellgren-Lawrence 1.0 to 1.5. MOCART scores at the final follow-up averaged 71 (10 to 95). Graft-type analysis demonstrated an increased rate of graft-related SAE in dry-AC and media-AC, but their final outcomes were equivalent. Cellular data of AC at the implantation were as follows: cells in suspension 9.2 × 106, viability 95%. In blood-fBMSC group, a cell suspension with 87% viability was injected, which contained 1156 CFU-Fs. CONCLUSION: CHAS with intra-operative seeding of active cells, either AC or fBMSC, led to an overall successful outcome for the treatment of chronic osteochondral lesions in the knee. Blood soaking of CHAS in situ before cell seeding significantly decreased early post-operative adverse events, such as synovitis and arthrofibrosis.

Patient-reported joint status and quality of life in sports-related ankle disorders and osteoarthritis.

PURPOSE: To compare self-reported joint status, quality of life, level of activity and pain management in patients scheduled for surgical treatment of seven common ankle disorders: osteoarthritis (OA), primary osteochondral lesion of talus (P-OLT), recurrent osteochondral lesion of talus (R-OLT), lateral ankle instability (INST) and anterior (ANT-IMP), posterior (POST-IMP) and combined (COMB-IMP) ankle impingements. METHODS: The cross-sectional study design was implemented. Hospital records of 610 patients that were admitted for surgical intervention on the ankle joint over a seven year period were reviewed. Patient selection (over 18 years, no systemic musculoskeletal illnesses, only one isolated ankle pathology) resulted in 123 eligible patients for current study (OA 22, P-OLT 19, R-OLT 18, INST 15, ANT-IMP 20, POST-IMP 13, COMB-IMP 16). Foot and Ankle Outcome Score (FAOS), European quality of life in a visual analogue and in five dimensions (EQ-VAS, EQ-5D-3L), Tegner activity scale (TAS) and pain medication usage were recorded at the admission and compared across these seven groups. RESULTS: All evaluated ankle disorders induced the following: (a) subjective joint-specific dysfunction - FAOS cumulative: 42 (OA), 50 (R-OLT), 65 (P-OLT), 65 (INST), 63 (ANT-IMP), 61 (POST-IMP), 60 (COMB-IMP); (b) decreased quality of life - EQ-5D-3L: 0.41 (OA), 0.44 (R-OLT), 0.56 (P-OLT), 0.62 (INST), 0.64 (ANT-IMP), 0.56 (POST-IMP), 0.60 (COMB-IMP) and (c) decreased activity level - TAS: 2.1 (OA), 2.7 (R-OLT), 3.7 (P-OLT), 4.0 (INST), 4.7 (ANT-IMP), 4.4 (POST-IMP), 5.1 (COMB-IMP). FAOS subscales, EQ-5D-3L and TAS were significantly lower in OA and R-OLT patients. Between 31% (POST-IMP) and 68% (OA and R-OLT) of patients required pain medication over one month prior to the assessment. CONCLUSION: All analysed ankle disorders in patients amenable for surgical treatment induced a considerable decline in patients` perceived ankle function, quality of life and activity level. The worst subjective ankle status was reported equally by OA and R-OLT patients, while patients with the other five disorders reported comparable values.

Treatment of hallux rigidus by a novel bi-phasic aragonite-based implant: results of a two year multi-centre clinical trial.

PURPOSE: The two year results of a multi-centre clinical trial were examined to evaluate surgical treatment of hallux rigidus using a novel, bi-phasic, biodegradable, and cell-free aragonite-based scaffold (Agili-C™, CartiHeal Ltd, Israel). METHODS: Twenty patients with moderate-to-severe hallux rigidus were recruited. After thorough metatarsophalangeal joint (MTPJ-1) debridement, the scaffolds were implanted into the defect centre. Eight patients received concomitant osteotomy. Treatment outcome was followed clinically (Pain VAS, FAAM-ADL, FAAM-Sport, AOFAS-HMIS, maximum active range of extension ROM-EXT, and flexion ROM-FLEX), and by medical imaging, at six month intervals for two years. Adverse events were recorded throughout the study follow-up period. RESULTS: Significant clinical improvement over time was observed in all evaluated parameters (screening to final evaluation averages: Pain VAS 59 to 26, FAAM-ADL 57 to 77, FAAM-Sport 39 to 66, AOFAS-HMIS 51 to 81, ROM-EXT 18° to 36°), except for ROM-FLEX. Radiographs showed stable MTPJ-1 width over the two years in 17/18 cases (94%). MRI demonstrated progressive implant biodegradation, coupled with articular cartilage and subchondral bone regeneration, with a repair tissue defect fill of 75-100% in 14/17 (82%) subjects at their final visit. Revision surgery with implant removal was performed in two patients. CONCLUSION: Bi-phasic, osteochondral, biodegradable, aragonite-based scaffold demonstrated positive clinical outcome and a good safety profile in the treatment of medium-to-advanced hallux rigidus. According to the medical imaging, this implant has the potential to restore the entire osteochondral unit of metatarsal head.

Complex Osteochondral Lesions of the Talus Treated With a Novel Bi-Phasic Aragonite-based Implant.

To present initial results of a novel, bi-phasic, porous, biodegrade, and cell-free aragonite-based scaffold for treating complex osteochondral lesions of the talus (OLT). Four subjects (2 males and 2 females; 34-61 years old) were operated on their ankles due to chronic and deep OLT-Hepple grades 4 or 5 (1.8-2.2 cm2). Three subjects had OLT on the medial central trochlea, and 1 had a combined medial and lateral lesions. OLT were exposed through medial malleolus osteotomy, with an additional lateral arthrotomy in the combined lesions. Bi-phasic porous osteochondral scaffolds (single implant or 2 implants) were implanted in a press-fit manner using a designated surgical toolset. Treatment outcome was followed clinically (Foot and Ankle Outcome Score, EQ-5D 3L, Tegner activity scale) and by medical imaging (radiographs, magnetic resonance imaging) from 18 to 32 months. All Foot and Ankle Outcome Score values increased from preoperative to final follow-up values (Symptoms 62 to 71, Pain 53 to 84, ADL 60 to 89, Sport 19 to 65, and QoL 18 to 47). EQ-5D 3L increased from 0.59 to 0.76, and Tegner activity values increased from 1.5 to 3. Kellgren-Lawrence ankle radiographic scores remained stable (2 to 2). Postoperative MR evaluation demonstrated cartilage defect fill of 75% to 100% respect to the native cartilage in 3 subjects (4 OLTs), while 1 lesion was filled 25% to 50%. No graft related serious adverse events or graft failures were reported. The use of a bi-phasic osteochondral biodegradable aragonite-based scaffold in the treatment of complex OLT during the reported period presented positive and promising clinical and radiologic outcome, without serious adverse events or graft failures.

Early clinical and neuromuscular properties in patients with normal or sub-normal subjective knee function after anterior cruciate ligament reconstruction.

PURPOSE: To determine clinical and neuromuscular properties in patients with normal or sub-normal subjective knee function after finalisation of 6 months' post-operative rehabilitation following anterior cruciate ligament reconstruction (ACLR). METHODS: Sixty patients after primary anatomical single-bundle hamstring ACLR were prospectively enrolled. Demographics, subjective, clinical and functional status of the injured knee were recorded at baseline, 6 and 12 months post-operatively. Return to pre-injury activities time (months) was monitored. Tensiomyography and isokinetic dynamometry of thigh muscles were performed at 6 months, when standard ACLR rehabilitation is finalized. Based on their IKDC Subjective Knee Evaluation scores at 6 months, they were assigned into "Normal" or "Sub-normal" group. All the above measured parameters were then compared between the two groups. RESULTS: At 6 months' timeline, 21 patients (35%) perceived their knee function as "Normal", while 39 (65%) were "Sub-normal". There were no differences in clinical status between both groups, but patients in Normal group achieved higher IKDC, Lysholm, Tegner scores as well as higher single-leg hop test. They were taller, had lower body mass index and more of them achieved their preinjury level of activity at 12 months (67% vs. 33%). Tensiomyography revealed higher biceps femoris as well as semitendinosus and semimembranosus radial displacement values on the operated leg in Normal group. Isokinetic dynamometry showed significantly higher normalised peak torque and average power of knee extensor muscles. CONCLUSIONS: Patients who perceive their knee function as normal at 6 months following ACLR presented with better neuromuscular properties of the thigh muscles. Decreased hamstring stiffness seems to be the key to higher return-to-preinjury activity. Postoperative rehabilitation should be more focused on reducing hamstring stiffness in addition to improving knee extensor muscle strength. Level of evidence II (prospective cohort study).

The influence of a sustained 10-day hypoxic bed rest on cartilage biomarkers and subchondral bone in females: The FemHab study.

This study assessed the influence of a 10-day hypoxic bed rest on cartilage biomarkers and subchondral bone density across the patellofemoral joint (PFJ). Within clinical settings hypoxic tissue may arise in several types of disorders. Furthermore, a hypoxic environment is being considered for space flight habitats in the near future. Female participants (N = 12) participated in this study comprising three 10-day interventions: hypoxic ambulation (HAMB), normoxic bed rest (NBR), and hypoxic bed rest (HBR). Venous samples were collected prior to (day -2: Pre) and during the intervention (days 2 and 5), immediately before reambulation (D11) and 24 hr post intervention (R1). Blood samples were analyzed for: aggrecan, hyaluronan, Type IIA procollagen amino terminal propeptide (PIIANP), and cartilage oligomeric matrix protein (COMP). Total bone mineral density (BMD) in eight regions (2 mm × 10 mm) across the PFJ was determined. The three interventions (HAMB, HBR, and NBR) did not induce any significant changes in the cartilage biomarkers of hyaluronan or PIIANP. Aggrecan increased during the HAMB trial to 2.02 fold the Pre value. COMP decreased significantly in both NBR & HBR compared to HAMB on D5. There were significant differences in BMD measured across the PFJ from cortical patellar bone (735 to 800 mg/cm3 ) to femur trabecular (195 to 226 mg/cm3 ). However, there were no significant changes in BMD from Pre to Post bed rest. These results indicate that there were no significant detectable effects of inactivity/unloading on subchondral bone density. The biomarker of cartilage, COMP, decreased on D5, whereas the addition of hypoxia to bed rest had no effect, it appears that hypoxia in combination with ambulation counteracted this decrease.