Fibronectin-coating enhances attachment and proliferation of mesenchymal stem cells on a polyurethane meniscal scaffold.

INTRODUCTION: Partial meniscectomy is one of the most common surgical strategy for a meniscal injury, but sometimes, patients complain of knee pain due to an overload in the ablated compartment. In these cases, implantation of tissue engineering scaffold could be indicated. Currently, two commercial scaffolds, based on collagen or polycaprolactone-polyurethane (PCL-PU), are available for meniscus scaffolding. In short term follow-up assessments, both showed clinical improvement and tissue formation. However, long-term studies carried out in PCL-PU showed that the new tissue decreased in volume and assumed an irregular shape. Moreover, in some cases, the scaffold was totally reabsorbed, without new tissue formation.Mesenchymal stem cells (MSCs) combined with scaffolds could represents a promising approach for treating meniscal defects because of their multipotency and self-renewal. In this work, we aimed to compare the behaviour of MSCs and chondrocytes on a PCL-PU scaffold in vitro. MSCs express integrins that binds to fibronectin (FN), so we also investigate the effect of a FN coating on the bioactivity of the scaffold. METHODS: We isolated rabbit bone marrow MSCs (rBM-MSCs) from two skeletally mature New Zealand white rabbits and stablished the optimum culture condition to expand them. Then, they were seeded over non-coated and FN-coated scaffolds and cultured in chondrogenic conditions. To evaluate cell functionality, we performed an MTS assay to compare cell proliferation between both conditions. Finally, a histologic study was performed to assess extracellular matrix (ECM) production in both samples, and to compare them with the ones obtained with rabbit chondrocytes (rCHs) seeded in a non-coated scaffold. RESULTS: A culture protocol based on low FBS concentration was set as the best for rBM-MSCs expansion. The MTS assay revealed that rBM-MSCs seeded on FN-coated scaffolds have more cells on proliferation (145%; 95% CI: 107%-182%) compared with rBM-MSCs seeded on non-coated scaffolds. Finally, the histologic study demonstrated that rCHs seeded on non-coated scaffolds displayed the highest production of ECM, followed by rBM-MSCs seeded on FN-coated scaffolds. Furthermore, both cell types produced a comparable ECM pattern. CONCLUSION: These results suggest that MSCs have low capacity attachment to PCL-PU scaffolds, but the presence of integrin alpha5beta1 (FN-receptor) in MSCs allows them to interact with the FN-coated scaffolds. These results could be applied in the design of scaffolds, and might have important clinical implications in orthopaedic surgery of meniscal injuries.

A Nomogram-Based Prognostic Model for Advanced Hepatocellular Carcinoma Patients Treated with Sorafenib: A Multicenter Study.

Among scores and staging systems used for HCC, none showed a good prognostic ability in patients with advanced HCC treated with Sorafenib. We aimed to evaluate predictive factors of overall survival (OS) and drug response in HCC patients undergoing Sorafenib included in the Italian Liver Cancer (ITA.LI.CA.) multicenter cohort. Patients in the ITA.LI.CA database treated with Sorafenib and updated on 30 June 2019 were included. Demographic and clinical data before starting Sorafenib treatment were considered. For the evaluation of predictive factors for OS, a time-dependent Cox proportional hazard model was used. A total of 1107 patients were included in our analysis. The mean age was 64.3 years and 81.7% were male. Most patients were staged as BCLC B (205, 18.9%) or C (706, 65.1%). The median time of Sorafenib administration was 4 months (interquartile range (IQR) 2-12), and the median OS was 10 months (IQR: 4-20). A total of 263 patients (33.8%) out of 780 with available evaluation experienced objective tumoral response to Sorafenib. The Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (hazard ratio (HR) 1.284), maximum tumoral diameter (HR 1.100), plasma total bilirubin (HR 1.119), aspartate amino transferase assessed as multiple of the upper normal value (HR 1.032), alpha-fetoprotein ≥200 ng/mL (HR 1.342), hemoglobin (HR 0.903) and platelet count (HR 1.002) were associated with OS at multivariate Cox regression analysis. Drug response was predicted by maximum tumoral diameter and platelet count. A novel prognostic nomogram for patients undergoing Sorafenib is hereby proposed. The novelty introduced is the comprehensive patient's assessment using common markers of patient's general status, liver damage and function and HCC biology. Further studies are required to test its accuracy and provide external validation.

Polyurethane Meniscal Scaffold: Does Preoperative Remnant Meniscal Extrusion Have an Influence on Postoperative Extrusion and Knee Function?

Meniscal extrusion (ME) has been identified as a risk factor in the development of knee osteoarthritis. The relevance of this finding when a meniscal scaffold is used has not been extensively studied. The objective of this study was to determine whether preoperative meniscal remnant extrusion (MRE) was correlated with postoperative scaffold extrusion (SE) or with functional outcomes at the 2-year follow-up. Retrospective study included all polyurethane scaffolds implanted with a minimum 2-year follow-up. A magnetic resonance imaging (MRI) was performed preoperatively and postoperatively at 2 years. Extrusion was measured in millimeters in a coronal view. Patients were assigned to either group 1 or 2 depending on the preoperative MRE being either <3 mm (minor extrusion) or 3 mm (major extrusion). Functional outcomes were analyzed by means of the Western Ontario Meniscal Evaluation Tool (WOMET), International Knee Documentation Committee, Kujala and Tegner scores, as well as visual analog scale. Satisfaction was also documented. Sixty-two out of 98 patients were available to undergo an MRI at final follow-up. The mean age was 41.3 years (range, 17-58) and the mean follow-up was 45 months (range, 25-69). The mean preoperative MRE was 2.8 mm (standard deviation [SD] 1.2) and the mean postoperative SE was 3.8 mm (SD 1.8) (p < 0.01). All functional scores improved during the study period. When the correlation (Spearman's rho) between the difference in extrusion between the pre 26 and postoperative periods and their correlation with the different scores was assessed, correlation was only observed in the WOMET (rho 0.61, p = 0.02). The preoperative MRE in Group 1 was 1.85 mm (SD 0.83) and 3.7 mm (SD 2.2) in Group 2 (p < 0.01). At final follow-up, SE was 3.86 mm (SD 0.7) in Group 1, whereas it was 3.98 mm (SD 1) in Group 2 (p = 0.81). No differences were observed in the scores used for these two groups. The SE observed at the 2-year follow-up after the implantation of a polyurethane scaffold did not depend on preoperative MRE (major or minor extrusion). The WOMET score, which was the only meniscal-specific functional scored used, showed some inferior results in the most extruded meniscal scaffolds. This is a retrospective case series. Level of evidence is 4.

Magnetic Resonance Imaging and Functional Outcomes After a Polyurethane Meniscal Scaffold Implantation: Minimum 5-Year Follow-up.

PURPOSE: To report the magnetic resonance imaging (MRI) and clinical outcomes at a minimum 5-year follow-up in a series of patients with postmeniscectomy syndrome and treated with a polyurethane scaffold. METHODS: All consecutive patients operated on from September 2008 to February 2011 for either persistent medial or lateral joint line compartmental pain receiving a polyurethane scaffold due to a previous partial meniscus resection with a minimum 5-year follow-up were included. Functional scores (Knee Injury and Osteoarthritis Outcomes Score, International Knee Documentation Committee, Lysholm, and Tegner) were assessed preoperatively and at the last follow-up. The state of the scaffold as well as postoperative scaffold extrusion and the total remaining meniscal volume was also evaluated in MRI. RESULTS: Thirty-two patients were included. The mean follow-up was 70.8 ± 7.5 months. The functionality of the knees improved in all the scores used (P < .001) except for the Tegner score that stayed steady. Most of meniscal implants showed extrusion of 2.4 mm (95% confidence interval [CI], 1.1-3.7) were smaller and a hyperintensity signal was seen in the MRI. Three scaffolds were resorbed at the last follow-up. The meniscal volume, determined by MRI, was 1.14 cm3 (95% CI, 0.96-1.31) preoperatively and 1.61 cm3 (95% CI, 1.43-1.7) at the last follow-up. No differences were presented. CONCLUSIONS: The use of a polyurethane meniscal scaffold in patients with a symptomatic meniscus deficit had a good functional outcome at 5 years after surgery. However, the implanted scaffolds did not present normal meniscal tissue with MRI, and the implant volume was considerably less than expected. The fact that most of patients included received different concomitant procedures during scaffold implantation introduces a degree of performance bias into the results. LEVEL OF EVIDENCE: Level IV, case series.