Biomechanical and histological comparison of two suture configurations for soft tissue grafts: speedtrap™ versus krackow stitch.

To compare 2 different graft preparation techniques to determine biomechanical strength and resultant tissue trauma evaluated by histology. Twelve common flexors of the finger's tendons were prepared with either tubulization (SpeedTrap™) or transtendon stiches (Orthocord™). The stiffness, resistance and energy at maximum load were tested for biomechanical assessment in both groups. After load testing, Samples were stained with hematoxylin and eosin (HE) to evaluate histological damage. We observe that the time to prepare tendons with SpeedTrap™ was 8.3 times faster (1:25 min) than traditional ones (15:02 min). In all cases, the mean values for SpeedTrap™ were higher in terms of strength, stiffness and energy at maximum load than for traditional suture but without significant difference (p > 0.05). The Krackow stitch produces greater structural damage to the collagen fibers while SpeedTrap™ maintains better organized arrangement of the fibers after tubulization preparation. With the results obtained, we can conclude that the tubulization technique allows faster graft preparation with less structural damage to the manipulated tissue without altering the biomechanical resistance provided by the transtendon suture technique.

A modified animal-free serum technique for efficient isolation and proliferation of mesenchymal stem cells from Hoffa fat pad.

We focus on this study in designing an alternative technique for obtaining mesenchymal stem cells (MSCs) from residual tissue, Hoffa fat, in arthroscopic procedures. Two males and two females were included, and underwent knee arthroscopy; a sample of infrapatellar adipose tissue was obtained with basket forceps. The primary culture was made using the explant method and the culture media: DMEM-high glucose, supplemented with 10% of inactivated human allogeneic serum. All the cellular cultures remained under culture conditions for three weeks, after that by flow cytometry the cells were characterized by MSCs antibody panel: CD105, CD73 and CD90. Subsequently, in the first pass, the MSCs were cultured in commercial human chondrogenic, osteogenic and adipogenic mediums, respectively. After primary culture, we obtained on average 95,600.00 ± 7,233.26 cells/cm2, and the duplication time of MSCs isolate from Hoffa fat pad was established in 39 hours. By flow cytometry, we found that surface markers percentage for expanded MSCs (CD105, CD73, CD90) in primary culture significantly increased and its morphology was fibroblastic-like. After differentiation culture which was made in the first pass, by immunofluorescence, we obtained positive cell markers for three lineages of differentiation, adipocytes: LPL protein, osteocytes: RUNX2, Osteopontin, chondrocytes: SOX9, Aggrecan and COL2A1. We managed to isolate a significant number of MSCs from this source using an easy method to implement and minimal nutrient supplementation, with high potential for differentiation to mature mesenchymal tissues and potential use in basic experimental, preclinical and even clinical research.

Suitable characteristics in the selection of human allogeneic chondrocytes donors to increase the number of viable cells for cartilage repair.

Autologous chondrocyte implantation has shown optimal long-term outcomes in the treatment of cartilage lesions. The challenge for a single-stage approach lies in obtaining sufficient number of cells with high viability. The answer could lie in supplementing or replacing them with allogenic chondrocytes coming from cadaveric donors. In the present work, we aimed to compare the number of viable cells isolated from cartilage of live and cadaveric donors and to determine the suitable characteristics of the best donors. A total of 65 samples from donors aged from 17 to 55 years, either women or men, were enrolled in this study (33 living vs. 32 cadaveric). The mean time of hours from death to processing samples in cadaveric donors was higher compared to live donors (64.3 ± 17.7 vs. 4.6±6.4). The number of isolated chondrocytes per gram of cartilage was higher in cadaveric donors (5.389 × 106 compared to 3.067 × 106 in living donors), whereas the average of cell viability was comparable in both groups (84.16% cadaveric, 87.8% alive). It is possible to obtain viable chondrocytes from cartilage harvested from cadaveric donors, reaching a similar cell number and viability to that obtained from the cartilage of living donors.

Synovial membrane mesenchymal stem cells for cartilaginous tissues repair.

BACKGROUND: The present review is focused on general aspects of the synovial membrane as well as specialized aspects of its cellular constituents, particularly the composition and location of synovial membrane mesenchymal stem cells (S-MSCs). S-MSC multipotency properties are currently at the center of translational medicine for the repair of multiple joint tissues, such as articular cartilage and meniscus lesions. METHODS AND RESULTS: We reviewed the results of in vitro and in vivo research on the current clinical applications of S-MSCs, surface markers, cell culture techniques, regenerative properties, and immunomodulatory mechanisms of S-MSCs as well as the practical limitations of the last twenty-five years (1996 to 2021). CONCLUSIONS: Despite the poor interest in the development of new clinical trials for the application of S-MSCs in joint tissue repair, we found evidence to support the clinical use of S-MSCs for cartilage repair. S-MSCs can be considered a valuable therapy for the treatment of repairing joint lesions.

Osteogenic Potential of Monosodium Urate Crystals in Synovial Mesenchymal Stem Cells.

Background and Objectives: Deposits of monosodium urate (MSU) crystals due to increased levels of uric acid (UA) have been associated with bone formation and erosion, mainly in patients with chronic gout. The synovial membrane (SM) comprises several types of cells, including mesenchymal stem cells (SM-MSCs); however, it is unknown whether UA and MSU induce osteogenesis through SM-MSCs. Materials and Methods: Cultures of SM were immunotyped with CD44, CD69, CD90, CD166, CD105, CD34, and CD45 to identify MSCs. CD90+ cells were isolated by immunomagnetic separation (MACS), colony-forming units (CFU) were identified, and the cells were exposed to UA (3, 6.8, and 9 mg/dL) and MSU crystals (1, 5, and 10 µg/mL) for 3 weeks, and cellular morphological changes were evaluated. IL-1ß and IL-6 were determined by ELISA, mineralization was assessed by alizarin red, and the expression of Runx2 was assessed by Western blot. Results: Cells derived from SM and after immunomagnetic separation were positive for CD90 (53 ± 8%) and CD105 (52 ± 18%) antigens, with 53 ± 5 CFU identified. Long-term exposure to SM-MSCs by UA and MSU crystals did not cause morphological damage or affect cell viability, nor were indicators of inflammation detected. Mineralization was observed at doses of 6.8 mg/dL UA and 5 µg/mL MSU crystals; however, the differences were not significant with respect to the control. The highest dose of MSU crystals (10 µg/mL) induced significant Runx2 expression with respect to the control (1.4 times greater) and SM-MSCs cultured in the osteogenic medium. Conclusions: MSU crystals may modulate osteogenic differentiation of SM-MSCs through an increase in Runx2.

Ultrastructural changes in giant cell tumor of bone cultured cells exposed to quercetin.

Giant cell tumor of bone (GCTB) is a primary bone tumor that affects skeletally mature people and whose main treatment is surgical. Because there are few pharmacological alternatives for the treatment of this tumor to find other molecules or compounds that could be potential therapeutic agents is desirable. Quercetin is a flavonoid with described antitumoral effect in different types of cancer cell lines that could be a possible option in GCTB treatment. However, there is no literature about the effect of quercetin on GCTB. In the present paper, we reported the ultrastructural changes in GCTB cells exposed to quercetin and also determined the expression of RIP1K, Caspase 3 and Caspase 8 on the exposed cells. For this purpose, GCTB sample was obtained from one patient and cultured. Quercetin affected all the histological components of the GCTB. The ultrastructural changes consisted mainly in necroptosis, autophagocytosis and secondary necrosis. This is the first report about quercetin effects on giant cell tumor of bone cultured cells. Further studies in other models could be done to support the use of quercetin as a complementary treatment in giant cell tumor of bone.Abbreviations: Giant cell tumor of bone (GCTB); transmission electron microscopy (TEM); reverse transcription - polymerase chain reaction (RT-PCR); receptor interacting protein kinase 1 (RIP1K); Dulbecco's Modified Eagle's Medium (DMEM).

Hyperlipidemic microenvironment conditionates damage mechanisms in human chondrocytes by oxidative stress.

BACKGROUND: Currently, two pathogenic pathways describe the role of obesity in osteoarthritis (OA); one through biomechanical stress, and the other by the contribution of systemic inflammation. The aim of this study was to evaluate the effect of free fatty acids (FFA) in human chondrocytes (HC) expression of proinflammatory factors and reactive oxygen species (ROS). METHODS: HC were exposed to two different concentrations of FFA in order to evaluate the secretion of adipokines through cytokines immunoassays panel, quantify the protein secretion of FFA-treated chondrocytes, and fluorescent cytometry assays were performed to evaluate the reactive oxygen species (ROS) production. RESULTS: HC injury was observed at 48 h of treatment with FFA. In the FFA-treated HC the production of reactive oxygen species such as superoxide radical, hydrogen peroxide, and the reactive nitrogen species increased significantly in a at the two-dose tested (250 and 500 µM). In addition, we found an increase in the cytokine secretion of IL-6 and chemokine IL-8 in FFA-treated HC in comparison to the untreated HC. CONCLUSION: In our in vitro model of HC, a hyperlipidemia microenvironment induces an oxidative stress state that enhances the inflammatory process mediated by adipokines secretion in HC.

Co-culture of dedifferentiated and primary human chondrocytes obtained from cadaveric donor enhance the histological quality of repair tissue: an in-vivo animal study.

To compare the quality of the repair tissue in three-dimensional co-culture of human chondrocytes implanted in an in vivo model. Six cadaveric and five live human donors were included. Osteochondral biopsies from the donor knees were harvested for chondrocyte isolation. Fifty percent of cadaveric chondrocytes were expanded until passage-2 (P2) while the remaining cells were cryopreserved in passage-0 (P0). Fresh primary chondrocytes (P0f) obtained from live human donors were co-cultured. Three-dimensional constructs were prepared with a monolayer of passage-2 chondrocytes, collagen membrane (Geistlich Bio-Gide®), and pellet of non-co-cultured (P2) or co-cultured chondrocytes (P2 + P0c, P2 + P0f). Constructs were implanted in the subcutaneous tissue of athymic mice and left for 3 months growth. Safranin-O and Alcian blue staining were used to glycosaminoglycan content assessment. Aggrecan and type-II collagen were evaluated by immunohistochemistry. New-formed tissue quality was evaluated with an adaptation of the modified O'Driscoll score. Histological quality of non-co-cultured group was 4.37 (SD ±4.71), while co-cultured groups had a mean score of 8.71 (SD ±3.98) for the fresh primary chondrocytes and 9.57 (SD ±1.27) in the cryopreserved chondrocytes. In immunohistochemistry, Co-culture groups were strongly stained for type-II and aggrecan not seen in the non-co-cultured group. It is possible to isolate viable chondrocytes from cadaveric human donors in samples processed in the first 48-h of dead. There is non-significant difference between the numbers of chondrocytes isolated from live or cadaveric donors. Cryopreservation of cadaveric primary chondrocytes does not alter the capability to form cartilage like tissue. Co-culture of primary and passaged chondrocytes enhances the histological quality of new-formed tissue compared to non-co-cultured cells.

Cryopreserved CD90+ cells obtained from mobilized peripheral blood in sheep: a new source of mesenchymal stem cells for preclinical applications.

Mobilized peripheral blood (MPB) bone marrow cells possess the potential to differentiate into a variety of mesenchymal tissue types and offer a source of easy access for obtaining stem cells for the development of experimental models with applications in tissue engineering. In the present work, we aimed to isolate by magnetic activated cell sorting CD90+ cells from MPB by means of the administration of Granulocyte-Colony Stimulating Factor and to evaluate cell proliferation capacity, after thawing of the in vitro culture of this population of mesenchymal stem cells (MSCs) in sheep. We obtained a median of 8.2 ± 0.6 million of CD90+ cells from the 20-mL MPB sample. After thawing, at day 15 under in vitro culture, the mean CD90+ cells determined by flow cytometry was 92.92 ± 1.29 % and cell duplication time determined by crystal violet staining was 47.59 h. This study describes for the first time the isolation, characterization, and post-in vitro culture thawing of CD90+ MSCs from mobilized peripheral blood in sheep. This population can be considered as a source of MSCs for experimental models in tissue engineering research.

Central compartment release versus lesser trochanter release of the iliopsoas tendon for the treatment of internal snapping hip: a comparative study.

PURPOSE: To evaluate the results of 2 different techniques of endoscopic iliopsoas tendon release in the treatment of internal snapping hip syndrome. METHODS: Between January 2008 and January 2012, a consecutive series of patients with the diagnosis of internal snapping hip syndrome were treated with endoscopic release of the iliopsoas tendon. The patients were divided into 2 groups according to the surgical technique used. Group 1 was treated with endoscopic iliopsoas tendon release at the lesser trochanter, and group 2 was treated with iliopsoas release from the central compartment. Hip arthroscopy of both the central and peripheral compartments was performed in both groups by the lateral approach. Associated injuries were identified and treated arthroscopically. The postoperative physical therapy protocol was the same for both groups. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were evaluated preoperatively and at last follow-up at a minimum of 24 months. RESULTS: Twenty patients were included in the study: 6 in group 1 (4 male and 2 female patients; mean age, 35.6 years) and 14 in group 2 (5 male and 9 female patients; mean age, 32.7 years). Associated injuries were found and treated in 4 patients in group 1 and 10 patients in group 2. Every patient in both groups had an improvement in the WOMAC score. One patient in group 2 presented with recurrence of snapping that required surgical intervention. No complications were seen. CONCLUSIONS: Both central compartment release and release at the lesser trochanter produced favorable results, based on WOMAC scores, for the treatment of internal snapping hip syndrome. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Effect of smoking on the redox status of knee osteoarthritis: A preliminary study.

Even though smoking has been scarcely studied in osteoarthritis (OA) etiology, it is considered a controversial risk factor for the disease. Exposure to tobacco smoke has been reported to promote oxidative stress (OS) as part of the damage mechanism. The aim of this study was to assess whether smoking increases cartilage damage through the generation of OS. Peripheral blood (PB) and synovial fluid (SF) samples from patients with OA were analyzed. The samples were stratified according to smoking habit, Kellgren-Lawrence score, pain, and cotinine concentrations in PB. Malondialdehyde (MDA), methylglyoxal (MGO), advanced protein oxidation products (APOPs), and myeloperoxidase (MPO) were assessed; the activity of antioxidant enzymes such as gamma-glutamyl transferase (GGT), glutathione S-transferase (GST) and catalase (CAT), as well as the activity of arginase, which favors the destruction of cartilage, was determined. When stratified by age, for individuals <60 years, the levels of MDA and APOPs and the activity of MPO and GST were higher, as well as antioxidant system activity in the smoking group (OA-S). A greater degree of pain in the OA-S group increased the concentrations of APOPs and arginase activity (P < 0.01 and P < 0.05, respectively). Arginase activity increased significantly with a higher degree of pain (P < 0.01). Active smoking can be an important risk factor for the development of OA by inducing systemic OS in young adults, in addition to reducing antioxidant enzymes in older adults and enhancing the degree of pain and loss of cartilage.

The Critical Role of Hypoxia in the Re-Differentiation of Human Articular Chondrocytes.

The preservation of the chondrogenic phenotype and hypoxia-related physiological microenvironment are major challenges in the 2D culture of primary human chondrocytes. To address this problem, we develop a 3D culture system generating scaffold-free spheroids from human chondrocytes. Our results highlight the chondrogenic potential of cultured human articular chondrocytes in a 3D system combined with hypoxia independently of the cartilage source. After 14 days of culture, we developed spheroids with homogenous diameter and shape from hyaline cartilage donors. Spheroids generated in hypoxia showed a significantly increased glycosaminoglycans synthesis and up-regulated the expression of SOX9, ACAN, COL2A1, COMP, and SNAI1 compared to those obtained under normoxic conditions. Therefore, we conclude that spheroids developed under hypoxic conditions modulate the expression of chondrogenesis-related genes and native tissue features better than 2D cultures. Thus, this scaffold-free 3D culture system represents a novel in vitro model that can be used for cartilage biology research.

Free Hand Drilling Technique to Enhance Central Position of Tunnels in Arthroscopic Acromioclavicular Joint Fixation Using TightRope System.

Acromioclavicular joint (ACJ) dislocations represent one of the most common lesions in the shoulder. Arthroscopic reduction and ACJ fixation with the button system is one of the most used techniques for displaced and unstable dislocations. Difficulties with placing the tunnels in the central and correct position of the clavicular and coracoid can occur with the use of a guide, which can result in fractures, eccentric tunnel position, cortical rupture, prolongation of surgical times with its complications as bleeding, tissue infiltration, difficult visualization, and increased risk of infection. Prior free hand central tunnel placement in the clavicle with a 3.2 mm drill helps to keep in place the pin guide over the superior cortical of coracoid with reduction of guide movement to enhance the correct position of tunnel in the coracoid process avoiding bone complications.

Arthroscopic Treatment of Patellar and Trochlear Cartilage Lesions with Matrix Encapsulated Chondrocyte Implantation versus Microfracture: Quantitative Assessment with MRI T2-Mapping and MOCART at 4-Year Follow-up.

METHODS: Seventeen patients aged 18 to 55 years with symptomatic full-thickness cartilage lesions on either patella or trochlea were treated with matrix autologous chondrocyte implantation (MACI) or microfracture (MF). Both procedures combined with unloading/realigning techniques. Clinical assessment and T2-mapping were evaluated at 48-months. RESULTS: Clinically results from pre-op to 48-months improved significantly in MACI and MF for Lysholm (p = 0.001, p = 0.001), IKDC-S (p = 0.001, p = 0.002), KOOS-P (p = 0.000, p = 0.002), KOOS-DLA (p = 0.002, p = 0.003), KOOS-Sports/Rec (p = 0.000, p = 0.004), KOOS-QoL (p = 0.000, p = 0.003), KOOS-symptoms (p = 0.001, p = 0.020), and Kujala (p = 0.000, p = 0.01), respectively. Tegner was significant between baseline and 48 months only for MACI (p < 0.008) compared with MF (p = 0.25). No significant difference was observed between groups for any score at 3, 12, 24, and 48-months (p > 0.05). T2-mapping values improved significantly over time in MACI compared with MF at 24 months (39.35 vs. 50.44, p = 0.007) and 48 months (36.54 vs. 48.37, p = 0.005). When comparing control values to MACI at 12-m (p = 0.714), 24-m (p = 0.175), and 48-m (p = 0.097), no significant difference was found. MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score comparison gave no statistical difference between groups. CONCLUSIONS: Clinically both techniques improved significantly over time. However, quantitative assessment showed that only newly formed tissue with MACI technique improves significantly since 12-months and maintains stable values compared with native cartilage until 48-month follow-up. MF results were never comparable to those native values. Level of evidence II.

Anterior Tibial Tendon Side-to-Side Tenorrhaphy after Posterior Tibial Tendon Transfer: A Technique to Improve Reliability in Drop Foot after Common Peroneal Nerve Injury.

Common peroneal nerve injury is present in 40% of knee dislocations, and foot drop is the principal complication. Posterior tibial tendon transfer is a viable solution to replace the function of the anterior tibial tendon (ATT) in the mid-foot. Several techniques for posterior tibial tendon transfer exist today, with variable results reported. However, adding augmentation with side-to-side tenorrhaphy of ATT to the transferred posterior tibial tendon (PTT) enhances anterior tissue balance and load sharing stress between native ATT enthesis and PTT tenodesis, allowing early rehabilitation and improving functional outcomes. Side-to-side tenorrhaphy is performed after PTT tenodesis in the lateral cuneiform to improve reliability in foot drop. This technique allows shorter immobilization time (from 6 to 2 weeks), earlier rehabilitation, sooner weight-bearing, and decreased risk of arthrofibrosis, scar formation, and muscle atrophy.

A novel model to culture cells from giant cell tumor of bone using three-dimensional (3D) polycaprolactone scaffold.

Two-dimensional (2D) culture of cells from giant cell tumor of bone (GCTB) is affected by loss of the multinucleated giant cells in subsequent passages. Therefore, there is limited time to study GCTB with all its histological components in 2D culture. Here, we explored the possibility of culturing GCTB cells on a polycaprolactone (PCL)-printed scaffold. We also evaluated the viability of the cultured cells and their adherence to the PCL scaffold at day 14 days using immunofluorescence analysis with calcein, vinculin, and phalloidin. Using the histological technique with hematoxylin and eosin staining, we observed all the histological components of GCTB in this 3D model. Immunohistochemical assays with cathepsin K, p63, and receptor activator of nuclear factor (NF)-κB ligand (RANKL) yielded positive results in this construct, which allowed us to confirm that the seeded cells maintained the expression of GCTB markers. Based on these findings, we concluded that the PCL scaffold is an efficient model to culture GCTB cells, and the cell viability and adherence to the scaffold can be preserved for up to 14 days. Moreover, this model can also be used in subsequent studies to assess in vitro cell-cell interactions and antineoplastic efficacy of certain agents to establish a treatment against GCTB.

Arthroscopic Matrix-Encapsulated Autologous Chondrocyte Implantation: A Pilot Multicenter Investigation in Latin America.

Objective. To evaluate minimum biosecurity parameters (MBP) for arthroscopic matrix-encapsulated autologous chondrocyte implantation (AMECI) based on patients' clinical outcomes, magnetic resonance imaging (MRI) T2-mapping, Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and International Cartilage Repair Society (ICRS) second-look arthroscopic evaluation, laying the basis for a future multicenter study. Design. Pilot clinical study. We analyzed the logistics to perform AMECI to treat focal chondral lesions in different hospitals following strict biosecurity parameters related to tissue and construct transportation, chondrocyte isolation, and cell expansion. Patient progress was analyzed with patient-reported outcome measures, MRI T2-mapping, MOCART, and ICRS arthroscopic second-look evaluation. Results. Thirty-five lesions in 30 patients treated in 7 different hospitals were evaluated. Cell viability before implantation was >90%. Cell viability in construct remnants was 87% ± 11% at 24 hours, 75% ± 17.1% at 48 hours, and 60% ± 8% at 72 hours after implantation. Mean final follow-up was 37 months (12-72 months). Patients showed statistically significant improvement in all clinical scores and MOCART evaluations. MRI T2-mapping evaluation showed significant decrease in relaxation time from 61.2 ± 14.3 to 42.9 ± 7.2 ms (P < 0.05). Arthroscopic second-look evaluation showed grade II "near normal" tissue in 83% of patients. Two treatment failures were documented. Conclusions. It was feasible to perform AMECI in 7 different institutions in a large metropolitan area following our biosecurity measures without any implant-related complication. Treated patients showed improvement in clinical, MRI T2-mapping, and MOCART scores, as well as a low failure rate and a favorable ICRS arthroscopic evaluation at a mid-term follow-up. Level of Evidence. 2b.

Soluble inflammatory mediators of synoviocytes stimulated by monosodium urate crystals induce the production of oxidative stress, pain, and inflammation mediators in chondrocytes : Secretome of synoviocytes induces chondrocyte damage.

We hypothesized that the secretion of inflammatory mediators from synoviocytes affects the chondrocyte homeostasis of articular cartilage. This study was a preliminary attempt to elucidate the molecular mechanisms by which soluble mediators obtained from activated synoviocytes induce oxidative stress and inflammation in chondrocytes. We measured the concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), nerve growth factor (NGF), superoxide anion (O2•-), hydrogen peroxide (H2O2), and nitric oxide (NO•) from articular human cells. First, we created a conditional basal medium by exposing synoviocytes (HS) to monosodium urate crystals (CBM). The chondrocytes were exposed to either CBM (CCM), urate crystals directly (CMSU), or remained untreated (CC) as a negative control. Data were analyzed by ANOVA tests; Bonferroni test was performed for multiple comparisons between groups. Interestingly, we observed that mediators of inflammation and oxidative stress were significantly higher in CCM than CMSU and CC groups (P<0.01). The specific concentrations were as follows: 19.85 ng/mL of IL-6, 9.79 ng/mL of IL-8, 5.17 ng/mL of NGF, and 11.91 ng/mL of MCP-1. Of note, we observed the same trend for reactive oxygen and nitrogen species (P<0.001). Soluble mediators secreted by synoviocytes after being activated with MSU crystals (as observed in individuals who present gout attacks) trigger chondrocyte activation intensifying the articular inflammatory, oxidative, and pain states that damage cartilage in OA; this damage is more severe even when compared to HC directly exposed to monosodium urate crystals. Key Points • The molecular relation between MSU depositions and cartilage damage could be mediated by pro-inflammatory soluble mediators and oxidative molecules. • The secretion of pro-inflammatory mediators by activated synoviocytes is more harmful to chondrocytes than a direct activation in the chondrocyte culture. • Under this model, there is an important imbalance in the matrix homeostasis due to changes in several chemokines, cytokines, and other factors such as NGF, as well as oxidative mediators.

First Clinical Application of Polyurethane Meniscal Scaffolds with Mesenchymal Stem Cells and Assessment of Cartilage Quality with T2 Mapping at 12 Months.

BACKGROUND: Complex meniscal lesions often require meniscectomy with favorable results in the short term but a high risk of early osteoarthritis subsequently. Partial meniscectomy treated with meniscal substitutes may delay articular cartilage degeneration. PURPOSE: To evaluate the status of articular cartilage by T2 mapping after meniscal substitution with polyurethane scaffolds enriched with mesenchymal stem cells (MSC) and comparison with acellular scaffolds at 12 months. METHODS: Seventeen patients (18-50 years) with past meniscectomies were enrolled in 2 groups: (1) acellular polyurethane scaffold (APS) or (2) polyurethane scaffold enriched with MSC (MPS). Patients in the MPS group received filgrastim to stimulate MSC production, and CD90+ cells were obtained and cultured in the polyurethane scaffold. The scaffolds were implanted arthroscopically into partial meniscus defects. Concomitant injuries (articular cartilage lesions or cartilage lesions) were treated during the same procedure. Changes in the quality of articular cartilage were evaluated with T2 mapping in femur and tibia at 12 months. RESULTS: In tibial T2 mapping, values for the MPS group increased slightly at 9 months but returned to initial values at 12 months (P > 0.05). In the APS group, a clear decrease from 3 months to 12 months was observed (P > 0.05). This difference tended to be significantly lower in the APS group compared with the MPS group at the final time point (P = 0.18). In the femur, a slight increase in the MPS group (47.8 ± 3.4) compared with the APS group (45.3 ± 4.9) was observed (P > 0.05). CONCLUSION: Meniscal substitution with polyurethane scaffold maintains normal T2 mapping values in adjacent cartilage at 12 months. The addition of MSC did not show any advantage in the protection of articular cartilage over acellular scaffolds (P > 0.05).

Arthroscopic Matrix-Assisted Autologous Chondrocyte Transplantation Versus Microfracture: A 6-Year Follow-up of a Prospective Randomized Trial.

BACKGROUND: Few randomized controlled trials with a midterm follow-up have compared matrix-assisted autologous chondrocyte transplantation (MACT) with microfracture (MFx) for knee cartilage lesions. PURPOSE: To compare the structural, clinical, and safety outcomes at midterm follow-up of MACT versus MFx for treating symptomatic knee cartilage lesions. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 48 patients aged between 18 and 50 years, with 1- to 4-cm2 International Cartilage Repair Society (ICRS) grade III to IV knee chondral lesions, were randomized in a 1:1 ratio to the MACT and MFx treatment groups. A sequential prospective evaluation was performed using magnetic resonance imaging (MRI) T2 mapping, the MOCART (magnetic resonance observation of cartilage repair tissue) score, second-look arthroscopic surgery, patient-reported outcome measures, the responder rate (based on achieving the minimal clinically important difference for the Knee injury and Osteoarthritis Outcome Score [KOOS] pain and KOOS Sport/Recreation), adverse events, and treatment failure (defined as a reoperation because of symptoms caused by the primary defect and the detachment or absence of >50% of the repaired tissue during revision surgery). RESULTS: Overall, 35 patients (18 MACT and 17 MFx) with a mean chondral lesion size of 1.8 ± 0.8 cm2 (range, 1-4 cm2) were followed up to a mean of 6 years postoperatively (range, 4-9 years). MACT demonstrated significantly better structural outcomes than MFx at 1 to 6 years postoperatively. At final follow-up, the MRI T2 mapping values of the repaired tissue were 37.7 ± 8.5 ms for MACT versus 46.4 ± 8.5 ms for MFx (P = .003), while the MOCART scores were 59.4 ± 17.3 and 42.4 ± 16.3, respectively (P = .006). More than 50% defect filling was seen in 95% of patients at 2 years and 82% at 6 years in the MACT group and in 67% at 2 years and 53% at 6 years in the MFx group. The second-look ICRS scores at 1 year were 10.7 ± 1.3 for MACT and 9.0 ± 1.8 for MFx (P = .001). Both groups showed significant clinical improvements at 6 years postoperatively compared with their preoperative status. Significant differences favoring the MACT group were observed at 2 years on the KOOS Activities of Daily Living (P = .043), at 4 years on all KOOS subscales (except Symptoms; P < .05) and the Tegner scale (P = .008), and at 6 years on the Tegner scale (P = .010). The responder rates at 6 years were 53% and 77% for MFx and MACT, respectively. There were no reported treatment failures after MACT; the failure rate was 8.3% in the MFx group. Neither group had serious adverse events related to treatment. CONCLUSION: Patients who underwent MACT had better structural outcomes than those who underwent MFx at 1 to 6 years postoperatively. Both groups of patients showed significant clinical improvements at final follow-up compared with their preoperative status. MACT showed superiority at 4 years for the majority of the KOOS subscales and for the Tegner scale at 4 to 6 years. The MACT group also had a higher responder rate and lower failure rate at final follow-up. REGISTRATION: NCT01947374 (ClinicalTrials.gov identifier).