Saris, Daniël B.F.

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.

Meniscus injuries can be highly debilitating and lead to knee osteoarthritis. Progenitor cells from the meniscus could be a superior cell type for meniscus repair and tissue-engineering. The purpose of this study is to characterize meniscus progenitor cells isolated by differential adhesion to fibronectin (FN-prog). Human osteoarthritic menisci were digested, and FN-prog were selected by differential adhesion to fibronectin. Multilineage differentiation, population doubling time, colony formation, and MSC surface markers were assessed in the FN-prog and the total meniscus population (Men). Colony formation was compared between outer and inner zone meniscus digest. Chondrogenic pellet cultures were performed for redifferentiation. FN-prog demonstrated multipotency. The outer zone FN-prog formed more colonies than the inner zone FN-prog. FN-prog displayed more colony formation and a higher proliferation rate than Men. FN-prog redifferentiated in pellet culture and mostly adhered to the MSC surface marker profile, except for HLA-DR receptor expression. This is the first study that demonstrates differential adhesion to fibronectin for the isolation of a progenitor-like population from the meniscus. The high proliferation rates and ability to form meniscus extracellular matrix upon redifferentiation, together with the broad availability of osteoarthritis meniscus tissue, make FN-prog a promising cell type for clinical translation in meniscus tissue-engineering.

Background: Long-term clinical evaluation of patient outcomes can steer treatment choices and further research for cartilage repair. Using mesenchymal stromal cells (MSCs) as signaling cells instead of stem cells is a novel approach in the field. Purpose: To report the 5-year follow-up of safety, clinical efficacy, and durability after treatment of symptomatic cartilage defects in the knee with allogenic MSCs mixed with recycled autologous chondrons in first-in-human study of 1-stage cartilage repair. Study Design: Case series; Level of evidence, 4. Methods: This study is an investigator-driven study aiming at the feasibility and safety of this innovative cartilage repair procedure. Between 2013 and 2014, a total of 35 patients (mean ± SD age, 36 ± 8 years) were treated with a 1-stage cartilage repair procedure called IMPACT (Instant MSC Product Accompanying Autologous Chondron Transplantation) for a symptomatic cartilage defect on the femoral condyle or trochlear groove. Subsequent follow-up after initial publication was performed annually using online patient-reported outcome measures with a mean follow-up of 61 months (range, 56-71 months). Patient-reported outcome measures included the KOOS (Knee injury and Osteoarthritis Outcome Score), visual analog scale for pain, and EuroQol–5 Dimensions. All clinical data and serious adverse events, including additional treatment received after IMPACT, were recorded. A failure of IMPACT was defined as a chondral defect of at least 20% of the index lesion with a need for a reintervention including a surgical procedure or an intra-articular injection. Results: Using allogenic MSCs, no signs of a foreign body response or serious adverse reactions were recorded after 5 years. The majority of patients showed statistically significant and clinically relevant improvement in the KOOS and all its subscales from baseline to 60 months: overall, 57.9 ± 16.3 to 78.9 ± 17.7 ( P < .001); Pain, 62.3 ± 18.9 to 79.9 ± 20.0 ( P = .03); Function, 61.6 ± 16.5 to 79.4 ± 17.3 ( P = .01); Activities of Daily Living, 69.0 ± 19.0 to 89.9 ± 14.9 ( P < .001); Sports and Recreation, 32.3 ± 22.6 to 57.5 ± 30.0 ( P = .02); and Quality of Life, 25.9 ± 12.9 to 55.8 ± 26.8 ( P < .001). The visual analog scale score for pain improved significantly from baseline (45.3 ± 23.6) to 60 months (15.4 ± 13.4) ( P < .001). Five cases required reintervention. Conclusion: This is the first study showing the midterm safety and efficacy of the proof of concept that allogenic MSCs augment 1-stage articular cartilage repair. The absence of serious adverse events and the clinical outcome support the longevity of this unique concept. These data support MSC-augmented chondron transplantation (IMPACT) as a safe 1-stage surgical solution that is considerably more cost-effective and a logistically advantageous alternative to conventional 2-stage cell-based therapy for articular chondral defects in the knee.

Objectives: Meniscal root disruption results in a loss of hoop strain resistance, increased articular cartilage contact pressure, and acceleration of degenerative changes. There is limited data comparing the outcomes of similarly matched patients with a medial meniscus posterior root tear treated with non-operative management, partial meniscectomy, or repair. The purpose of this study is to compare treatment failure, clinical outcome scores, and radiographic findings for a matched cohort of patients who underwent either non-operative management, partial meniscectomy, or transtibial pull-through repair for a medial meniscus posterior root tear (MMPRT). Our hypothesis is that patients who underwent meniscus root repair will have lower rates of progression to arthroplasty than patients who were treated with non-operative management or partial meniscectomy. Methods: Patients who underwent transtibial medial meniscus posterior horn root repair were matched by meniscus laterality, age, sex and K-L grades to patients treated non-operatively or with a partial meniscectomy. Progression to arthroplasty rates, IKDC and Tegner scores, and radiographic outcomes were analyzed between groups. Results: Forty-five patients were included in this study (15 non-operative, 15 partial meniscectomy, 15 root repair). Progression to arthroplasty demonstrated significant differences among treatment groups at a mean 74 months (non-operative 4/15, partial meniscectomy 9/15, meniscus repair 0/15, p=.0003). The meniscus root repair group had significantly less arthritic progression, as measured by change in K-L grade from pre-op to post-op (non-operative 1.0, partial mensicectomy 1.1, and meniscus repair 0.1, p=.001). Conclusion: Meniscus root repair leads to significantly less arthritis progression and subsequent knee arthroplasty compared to non-operative management and partial meniscectomy in a demographically matched cohort.

Objectives To examine the ability of surgeons to predict the outcome of treatment for meniscal tears by arthroscopic partial meniscectomy (APM) and exercise therapy in middle-aged patients. Design and setting Electronic survey. Orthopaedic surgeon survey participants were presented 20 patient profiles. These profiles were derived from a randomised clinical trial comparing APM with exercise therapy in middle-aged patients with symptomatic non-obstructive meniscal tears. From each treatment group (APM and exercise therapy), we selected five patients with the best (responders) and five patients with the worst (non-responders) knee function after treatment. 1111 orthopaedic surgeons and residents in the Netherlands and Australia were invited to participate in the survey. Interventions For each of the 20 patient profiles, surgeons (unaware of treatment allocation) had to choose between APM and exercise therapy as preferred treatment and subsequently had to estimate the expected change in knee function for both treatments on a 5-point Likert Scale. Finally, surgeons were asked which patient characteristics affected their treatment choice. Main outcomes The primary outcome was the surgeons’ percentage correct predictions. We also compared this percentage between experienced knee surgeons and other orthopaedic surgeons, and between treatment responders and non-responders. Results We received 194 (17%) complete responses for all 20 patient profiles, resulting in 3880 predictions. Overall, 50.0% (95% CI 39.6% to 60.4%) of the predictions were correct, which equals the proportion expected by chance. Experienced knee surgeons were not better in predicting outcome than other orthopaedic surgeons (50.4% vs 49.5%, respectively; p=0.29). The percentage correct predictions was lower for patient profiles of non-responders (34%; 95% CI 21.3% to 46.6%) compared with responders (66.0%; 95% CI 57.0% to 75.0%; p=0.01). In general, bucket handle tears, knee locking and failed non-operative treatment directed the surgeons’ choice towards APM, while higher level of osteoarthritis, degenerative aetiology and the absence of locking complaints directed the surgeons’ choice towards exercise therapy. Conclusions Surgeons’ criteria for deciding that surgery was indicated did not pass statistical examination. This was true regardless of a surgeon’s experience. These results suggest that non-surgical management is appropriate as first-line therapy in middle-aged patients with symptomatic non-obstructive meniscal tears. Clinical trial registration ClinicalTrials.gov Identifier: NCT03462134.

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.

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.