Potential of Melt Electrowritten Scaffolds Seeded with Meniscus Cells and Mesenchymal Stromal Cells.

Meniscus injury and meniscectomy are strongly related to osteoarthritis, thus there is a clinical need for meniscus replacement. The purpose of this study is to create a meniscus scaffold with micro-scale circumferential and radial fibres suitable for a one-stage cell-based treatment. Poly-caprolactone-based scaffolds with three different architectures were made using melt electrowriting (MEW) technology and their in vitro performance was compared with scaffolds made using fused-deposition modelling (FDM) and with the clinically used Collagen Meniscus Implants® (CMI®). The scaffolds were seeded with meniscus and mesenchymal stromal cells (MSCs) in fibrin gel and cultured for 28 d. A basal level of proteoglycan production was demonstrated in MEW scaffolds, the CMI®, and fibrin gel control, yet within the FDM scaffolds less proteoglycan production was observed. Compressive properties were assessed under uniaxial confined compression after 1 and 28 d of culture. The MEW scaffolds showed a higher Young's modulus when compared to the CMI® scaffolds and a higher yield point compared to FDM scaffolds. This study demonstrates the feasibility of creating a wedge-shaped meniscus scaffold with MEW using medical-grade materials and seeding the scaffold with a clinically-feasible cell number and -type for potential translation as a one-stage treatment.

The regenerative effect of different growth factors and platelet lysate on meniscus cells and mesenchymal stromal cells and proof of concept with a functionalized meniscus implant.

Meniscus regeneration could be enhanced by targeting meniscus cells and mesenchymal stromal cells (MSCs) with the right growth factors. Combining these growth factors with the Collagen Meniscus Implant (CMI®) could accelerate cell ingrowth and tissue formation in the implant and thereby improve clinical outcomes. Using a transwell migration assay and a micro-wound assay, the effect of insulin-like growth factor-1, platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor beta 1 (TGF-ß1), fibroblast growth factor, and platelet lysate (PL) on migration and proliferation of meniscus cells and MSCs was assessed. The formation of extracellular matrix under influence of the above-mentioned growth factors was assessed after 28 days of culture of both MSCs and meniscus cells. As a proof of concept, the CMI® was functionalized with a VEGF binding peptide and coated with platelet-rich plasma (PRP) for clinical application. Our results demonstrate that PDGF, TGF-ß1, and PL stimulate migration, proliferation, and/or extracellular matrix production of meniscus cells and MSCs. Additionally, the CMI® was successfully functionalized with a VEGF binding peptide and PRP which increased migration of meniscus cell and MSC into the implant. This study demonstrates proof of concept of functionalizing the CMI® with growth factor binding peptides. A CMI® functionalized with the right growth factors holds great potential for meniscus replacement after partial meniscectomy.

Secondary Meniscal Tears in Patients With Anterior Cruciate Ligament Injury: Relationship Among Operative Management, Osteoarthritis, and Arthroplasty at 18-Year Mean Follow-up.

BACKGROUND: Anterior cruciate ligament (ACL) injury is one of the most frequent orthopaedic injuries and reasons for time loss in sports and carries significant implications, including posttraumatic osteoarthritis (OA). Instability associated with ACL injury has been linked to the development of secondary meniscal tears (defined as tears that develop after the initial ACL injury). To date, no study has examined secondary meniscal tears after ACL injury and their effect on OA and arthroplasty risk. PURPOSE: To describe the rates and natural history of secondary meniscal tears after ACL injury and to determine the effect of meniscal tear treatment on the development of OA and conversion to total knee arthroplasty (TKA). STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A geographic database of >500,000 patients was reviewed to identify patients with primary ACL injuries between January 1, 1990, and December 31, 2005. Information was collected with regard to ACL injury treatment, rates/characteristics of the secondary meniscal tears, and outcomes, including development of OA and conversion to TKA. Kaplan-Meier and adjusted multivariate survival analyses were performed to test for the effect of meniscal treatment on survivorship free of OA and TKA. RESULTS: Of 1398 primary ACL injuries, the overall rate of secondary meniscal tears was 16%. Significantly lower rates of secondary meniscal tears were noted among patients undergoing acute ACL reconstruction within 6 months (7%) as compared with patients with delayed ACL reconstruction (33%, P < .01) and nonoperative ACL management (19%, P < .01). Of the 235 secondary meniscal tears identified (196 patients), 11.5% underwent repair, 73% partial meniscectomy, and 16% were treated nonoperatively. Tears were most often medial in location (77%) and complex in morphology (56% of medial tears, 54% of lateral tears). At the time of final follow-up, no patient undergoing repair of a secondary meniscal tear (0%) underwent TKA, as opposed to 10.9% undergoing meniscectomy and 6.1% receiving nonoperative treatment ( P = .28). CONCLUSION: Secondary meniscal tears after ACL injury are most common among patients undergoing delayed surgical or nonoperative treatment of their primary ACL injuries. Secondary tears often present as complex tears of the medial meniscus and result in high rates of partial meniscectomy.

Long-term Results After Repair of Isolated Meniscal Tears Among Patients Aged 18 Years and Younger: An 18-Year Follow-up Study.

BACKGROUND: Meniscal repair is desirable over resection to prevent postmeniscectomy arthritis, especially among young and active patients. However, long-term data are currently lacking following isolated meniscal repair, particularly in the pediatric population. PURPOSE/HYPOTHESIS: To report long-term follow-up of isolated meniscal tears treated by meniscal repair in a pediatric and adolescent population and to compare those results with previous midterm follow-up data reported. The authors hypothesized that these patients would have satisfactory function and reoperation rates at long-term follow-up. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Forty-four patients aged ≤18 years undergoing repair of an isolated meniscal tear (without concomitant anterior cruciate ligament injury) between 1990 and 2005 were included. At the time of final follow-up, recurrent tear, reoperations, and International Knee Documentation Committee (IKDC) and Tegner scores were determined. With logistic regression, the overall failure among tear types was calculated. Wilcoxon rank sum analysis were performed to calculate the differences in clinical outcome for different time points, and Spearman coefficients were calculated for Tegner and IKDC with different variables. RESULTS: At a mean follow-up of 17.6 years (range, 13.1-25.9 years), 32 patients with 33 isolated meniscal repairs (29 male, 3 female) with a mean age of 16.1 years (range, 9.9-18.7 years) at surgery were included in this study. At early follow-up, the overall failure rate was 14 of 33 (42%); complex tears (80%) and bucket-handle tears (47%) had higher overall failure rates when compared with simple tears (18.2%), although only complex tears had a significantly higher failure rate. However, no further failures occurred since midterm follow-up with any tear type. At final follow-up, the mean IKDC score was 92.3, which was significantly increased when compared with preoperative (65.3, P < .0001) and midterm (90.2, P = .01) scores. The mean Tegner score (6.5) was significantly lower than both preoperative (8.3, P < .0001) and midterm (8.4, P < .0001) scores. There was no difference in Tegner or IKDC score for patients with successful versus failed repair. CONCLUSION: In conclusion, while there was a high early failure rate, this study demonstrated overall good to excellent long-term clinical outcomes after isolated meniscal repair in an adolescent population, even for those requiring reoperation. Early failure and reoperation rates were variable, depending on tear type, with complex multiplanar tears having more failures at short-term follow-up. However, at long-term follow-up, IKDC and Tegner scores were not significantly different for those with complex tears as compared with other tear types.

Surgical Feasibility of a One-Stage Cell-Based Arthroscopic Procedure for Meniscus Regeneration: A Cadaveric Study.

IMPACT STATEMENT: Meniscus injury remains the most common indication for orthopedic surgery, but loss of functioning meniscus tissue is strongly correlated with development of early osteoarthritis. However, current clinical options for tissue engineering of the meniscus are limited. This study demonstrates the feasibility of combining human meniscus cells with mesenchymal stromal cells to enhance a meniscus scaffold for meniscus regeneration in a one-stage solution for partial meniscal deficiency.

Cell-Based Meniscus Repair and Regeneration: At the Brink of Clinical Translation?: A Systematic Review of Preclinical Studies.

BACKGROUND: Meniscus damage can be caused by trauma or degeneration and is therefore common among patients of all ages. Repair or regeneration of the menisci could be of great importance not only for pain relief or regaining function but also to prevent degenerative disease and osteoarthritis. Current treatment does not offer consistent long-term improvement. Although preclinical research focusing on augmentation of meniscal tear repair and regeneration after meniscectomy is encouraging, clinical translation remains difficult. PURPOSE: To systematically evaluate the literature on in vivo meniscus regeneration and explore the optimal cell sources and conditions for clinical translation. We aimed at thorough evaluation of current evidence as well as clarifying the challenges for future preclinical and clinical studies. STUDY DESIGN: Systematic review. METHODS: A search was conducted using the electronic databases of MEDLINE, Embase, and the Cochrane Collaboration. Search terms included meniscus, regeneration, and cell-based. RESULTS: After screening 81 articles based on title and abstract, 51 articles on in vivo meniscus regeneration could be included; 2 additional articles were identified from the references. Repair and regeneration of the meniscus has been described by intra-articular injection of multipotent mesenchymal stromal (stem) cells from adipose tissue, bone marrow, synovium, or meniscus or the use of these cell types in combination with implantable or injectable scaffolds. The use of fibrochondrocytes, chondrocytes, and transfected myoblasts for meniscus repair and regeneration is limited to the combination with different scaffolds. The comparative in vitro and in vivo studies mentioned in this review indicate that the use of allogeneic cells is as successful as the use of autologous cells. In addition, the implantation or injection of cell-seeded scaffolds increased tissue regeneration and led to better structural organization compared with scaffold implantation or injection of a scaffold alone. None of the studies mentioned in this review compare the effectiveness of different (cell-seeded) scaffolds. CONCLUSION: There is heterogeneity in animal models, cell types, and scaffolds used, and limited comparative studies are available. The comparative in vivo research that is currently available is insufficient to draw strong conclusions as to which cell type is the most promising. However, there is a vast amount of in vivo research on the use of different types of multipotent mesenchymal stromal (stem) cells in different experimental settings, and good results are reported in terms of tissue formation. None of these studies compare the effectiveness of different cell-scaffold combinations, making it hard to conclude which scaffold has the greatest potential.