Purpose

To demonstrate comparative KOOS Overall outcomes of an interpositional knee meniscus endoprosthesis versus non-surgical controls in the treatment of persistent post meniscectomy knee pain.

Methods and Materials

242 patients enrolled in a pooled population, randomized controlled trial (RCT) and single-arm study, comparing the investigational device to non-surgical standard of care. Of the first 100 patients enrolled, whose follow-up has exceeded 12 months, 65 patients were treated with the interpositional endoprosthesis device, and 35 were treated non-surgically. Validated KOOS scores at baseline, 6-week, 6-month, and 12-month time points were obtained from all patients. A “clinically significant improvement” was considered to be an increase of 20 KOOS points, (Roos et al.2003). The cohorts were compared at each time point using a two tailed t-test. All baseline cohort demographics and KOOS Overall score were not statistically different (p>0.05).

Results

Improvement in KOOS Overall for the investigational and control cohorts at 6-months and 12-months were 23.0 and 7.6 points, and 28.8 and 11.3 points, respectively (Figure 1). These data show a statistically significant improvement, above the clinically meaningful threshold, in the investigational arm versus the control arm as early as 6 months (p<0.001) and continues through the 12-month timepoint (p<0.001).

At 12 months, 3 (4.6%) investigational vs. 5 (14.3%) control patients were deemed study failures, due to removal of the investigational device, or due to non-surgical control patients requiring surgical intervention, At 12 months, more patients progressed to knee arthroplasty procedures in the non-surgical, control group (n=4, 11.4%) than in the surgical, investigational group (n=1, 1.5%).

Conclusion

These early one year follow-up results of efficacy KOOS Overall score are encouraging. Further study of the clinical outcomes of these patients and their adverse events is ongoing, with long-term results of both the randomized controlled trial and the single-arm study to be reported in the future.

Purpose

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 and Materials

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.

Purpose

To compare medial (MMRT) versus lateral meniscus posterior horn root tear (LMRT) injury presentation, treatment, clinical outcomes following root repair, and risk factors for failure.

Methods and Materials

One hundred and forty-one root tears in 137 patients were included. Radiographs were graded using Kellgren-Lawrence scores. MRI’s were reviewed for root tear classification and meniscus extrusion. Sub-analysis was performed on 62 patients who underwent root repair. Tegner, Lysholm, IKDC scores and progression to arthroplasty were analyzed in the repair groups. Patient demographics, radiographic findings, and clinical outcomes were compared between MMRT and LMRT.

Results

Of the 141 root tears, 109 were MMRTs, 30 were LMRTs, and two patients had both. At the time of injury, patients with MMRTs had a significantly higher age (MMRT=51.4 vs LMRT=24.6, p<.0001), BMI (MMRT=32.1 vs LMRT 25.8, P<.0001), KL score, (MMRT=1.3 vs LMRT=0.6, p<.0001), and higher rate of major meniscal extrusion (MMRT= 72% vs LMRT=20%, p<.0001). Of the 30 LMRT, 30/30 (100.0%) were treated with meniscal repair. With MMRT, 52/109 (48%) were treated non-operatively, 27/109 (25%) were treated with partial meniscectomy, and 30/109 (27%) were treated with meniscal repair. Sixty-two patients underwent meniscus root repair (30 medial, 30 lateral and 2 combined medial and lateral repairs) with an average 41 month follow-up. LMRT had significantly increased IKDC (LMRT=89.5, MMRT=80.4, p=0.02) and Tegner scores (LMRT=6.5, MMRT=5.1, p<0.05) compared to MMRT. LMRT repairs also had increased Lysholm scores, but the difference was not significant (LMRT=93.9, MMRT=89.6, p=0.20).

Conclusion

Compared to MMRTs, LMRTs occur in younger male patients with lower BMI, less cartilage degeneration, less extrusion on MRI, and more commonly with a ligament injury. While good to excellent clinical outcomes were attained in select patients for both medial and lateral meniscus root repair, LMRTs had overall better results after repair, likely due to differences in injury characteristics.

Purpose

Treatment of meniscal lesions is the most common surgical intervention performed by orthopaedic surgeons today. Favorable results have been reported in the short term after partial meniscectomy. However, the risk of osteoarthritis and irreversible damage occurring in the long term remains. Therefore, a novel, biodegradable, polyurethane scaffold was developed to fulfill an unmet clinical need in the treatment of patients with presenting with painful irreparable partial meniscal defects.

Methods and Materials

One hunderd and sixty four patients were consecutively treated for their partial meniscusdefects with the scaffold technique (Actifit). One hundert and fifty five patients were prospectively clinically evaluated with a follow-up of minimum 60 months. Magnetic resonance imaging (MRI) was used for morphologic analysis of the meniscal regeneration at 12, 24 and 60 months of follow-up.

Results

The patients included in this study showed a significant gradual clinical improvement after implantation of the scaffold. No effect of the scaffold on the opposing cartilage was observed on MRI. In 23 patients the treatment had failed (16,8%). Eighteen patients were lost to follow-up (11 %).

Conclusion

At five years post implantation, clinical outcome data from this study support the use of the polyurethane scaffold for the treatment of irreparable, painful, partial meniscus defects. However, well-designed, large-scale, randomized controlled trials are mandatory to confirm the initial results and the reliability of this procedure.

Purpose

The purposes of this study were to assess the repeatability of measuring meniscus extrusion using ultrasound, to measure the amount of medial meniscus extrusion using ultrasound, and to analyze knee kinematics of both intact knees and injured knees (complete posterior root tear) under various loading conditions using a combination of the robotic testing system and ultrasound.

Methods and Materials

Ten fresh frozen porcine knees were used. Intra- and inter-observer ultrasound agreement was assessed by calculating intra-class correlation coefficients (ICC).

A varus torque up to 5 Nm, an external torque up to 5 Nm, and an axial load up to 150N were individually applied to both intact knees and injured knee at 30°, 45°, 60°, and 90° of the knee flexion. Ultrasound examination was performed during each of the previous external loads and the amount of meniscus extrusion was measured.

Results

ICC demonstrated excellent intra- and inter-observer agreement in meniscus extrusion measurements. The amount of medial meniscus extrusion of intact knees under the unloaded condition was the smallest (1.2±0.6 mm) at 30°. When a varus torque was applied to the injured knee, meniscus extrusion was the largest (6.1±0.8 mm) at 90°. The difference in meniscus extrusion compared to the unloaded condition was largest in response to the varus torque at all knee flexion angles. A varus torque resulted in a significantly larger change in meniscus extrusion than an external torque at all flexion angles (all p<0.01) and an axial load at 30° (p=0.014).

Conclusion

Meniscus extrusion measurement using standardized ultrasound in combination with a robotic testing system has a high degree of repeatability. A complete posterior root tear changed knee kinematics, especially varus rotation, leading to an increase in medial meniscus extrusion. Regardless of meniscus injury status, meniscus extrusion increased with increased knee flexion angle.

Purpose

Pathological changes of the meniscus are common in people with Osteoartrithis (OA) and damage to the meniscus often leads to secondary OA. Meniscus architecture is individual and a perfect match is suggested to be key for successful transplantation. For this reason and due to the limited availability of donor meniscus other strategies such as 3D bioprinting is sought for.

Methods and Materials

Herein we 3D bioprinted a meniscus prototype including human induced pluripotent stem cells (iPSCs) together with human chondrocytes, using nanocellulose/alginate containing bioink previously published. Chondrocytes were obtained from autologous chondrocyte implantation (ACI) surgery and the iPSC line was generated by reprogramming the chondrocytes. CRISPER-Cas9 gene editing of the chondrocyte derived iPSC line was used to insert the green fluorescence protein (GFP) under control of the aggrecan promoter (ACAN). After printing the meniscus prototypes were placed in chondrogenic-differentiation medium for 3 weeks. Sections of the 3D bioprinted meniscus were stained by Alcian Blue van Gieson stainining. The aggrecan expression (ACAN) analysis of the 3D bioprinted iPSC/Chondrocytes was performed after 3 weeks using fluorescence imaging microscope IN Cell Analyzer 6000 (IN Cell 6000, GE Healthcare, United Kingdom).

Results

Meniscus-like tissue structures were reproducible obtained and could be scaled down and printed in 96 well format (Figure). Proteoglycan staining supported differentiation along the fibrous-cartilage lineage similar to what is normally seen in meniscus native tissue. The cartilage marker ACAN was induced in the GFP positive cells so that they can be traced back to the gene edited iPSCs and darker areas were assumed to originate from the human chondrocytes. Vascular-like tubes could be seen in sections and the surrounding endothelial cells were developed from the iPSC population based on visualization of GFP expression.

Conclusion

In this study we were able to produce a meniscus structure by 3D bioprinting multiple meniscus prototypes resembling native meniscus tissue.

Purpose

Damage to the meniscal hoop structure results in loss of biomechanical function. However, there have been no established, effective treatments for such injuries. The purpose of this study was to investigate the applicability of cell-seeded nanofibrous scaffolds to repair the damaged meniscal hoop structure along with the prevention of subsequent cartilage degeneration using a rabbit model.

Methods and Materials

Meniscal radial defects (5 mm width) in the medial meniscus were treated by wrapping and suturing with either an aligned electrospun nanofibrous scaffold alone (scaffold group, N=12) or a scaffold combined with a tissue engineered construct (TEC) derived from synovial mesenchymal stem cells (MSCs), (TEC-scaffold group, N=12), with the scaffold fiber direction matching that of the meniscal circumferential fibers. In the control group (N=12), no treatment was applied to the meniscal defect. Animals were euthanized at 4, 8, or 12 weeks after implant surgery. The distal femur and medial menisci of animals were used for histological analysis. As an evaluation of meniscal hoop function, the ratio of meniscal uncovered area on the medial tibial plateau is calculated.

Results

Histologically, the articular cartilage on the medial femoral condyles of both the control and scaffold group animals showed evidence for accelerated development of osteoarthritis-like changes (Fig.1). Conversely, the TEC-scaffold group maintained the integrity of the structure of the hyaline cartilage until 12 weeks after surgery. Notably, the meniscal uncovered areas for the TEC-scaffold group did not become statistically worse with time, suggesting repair and stabilization of hoop structure integrity over time (Fig.2). Also, meniscal defects treated with such TEC-combined nanofibrous scaffolds were consistently repaired with a fibrocartilaginous tissue.

Conclusion

In this study, we have demonstrated the feasibility of a combined TEC-nanofibrous scaffold to repair the meniscal hoop structure, and prevent the progression to cartilage degeneration, as a potential tissue engineering method.

Purpose

Meniscus tears are one of the most common knee injuries, with damage to the avascular region having poor healing potential. Partial meniscectomy is commonly used to treat meniscal tears but often leads to osteoarthritis (OA). Meniscus replacement strategies aimed at alleviating joint stress and preventing OA, including allografts or synthetic implants, suffer from either limited tissue availability or poor surgical performance. Our goal is to generate a 3D bioprinted partial meniscus implant with mechanical properties sufficient for arthroscopic surgical fixation, immediate load-bearing, and long-term performance to restore knee joint health and prevent the development of OA.

Methods and Materials

Novel blends of chitosan and polyvinyl alcohol (PVA) were bioprinted using the microfluidic RX1™ Bioprinter (Aspect Biosystems Ltd.). A composite implant was fabricated consisting of a meniscus-sized bioprinted chitosan/PVA mesh combined with a cast PVA solution. Suture pull-out strength, tensile strength, and compressive strength were measured using a Mach-1 mechanical testing device. Cadaveric porcine knees are being used to demonstrate compatibility with standard arthroscopic surgical procedures.

Results

Bioprinted chitosan/PVA blends exhibited high suture retention strength, tensile strength, elasticity, and recovery after mechanical deformation. Combining the bioprinted mesh with the cast PVA matrix into a "composite" tissue had a synergistic effect on mechanical performance compared to bioprinted-only or cast-only implants (Figure 1). Partial composite meniscus implants are being shuttled into the knee joint and fixated to the intact host peripheral meniscus tissue of cadaveric porcine knees to illustrate the feasibility of this surgical approach ex vivo (Figure 2).

Figure 1.

Figure 2.

Conclusion

A novel chitosan/PVA implant for partial meniscus replacement was developed using a unique microfluidic bioprinting technology. This bioprinted meniscus implant exhibits mechanical properties appropriate for arthroscopic surgical fixation and short-term load-bearing ex vivo and will be confirmed in vivo using a large animal model to study biological and mechanical performance.

Purpose

Although many strategies have been developed to modify the biological and biomechanical environment of the meniscal suture to improve the chances of healing, the failure rates remain high. Thus, new methods to promote meniscal regeneration and repair are needed. Administration of magnesium (via a repair using magnesium stitches) might enhance recruitment and adherence of
endogenous stem cells to the site of the lesion, thereby promoting in situ meniscal regeneration and chondroprotective functions.

Methods and Materials

Synovial fluid–derived mesenchymal stem cells (SMSCs) were identified and isolated from the knees of rabbits with a meniscal injury of 4 weeks’ duration. An in vitro analysis of adherence and chemotaxis of SMSCs was performed. For the in vivo assay, rabbits (n = 120) with meniscal lesions were divided into 3 groups: repair with high-purity magnesium stitches (Mg group), repair with absorbable sutures (Control group), and no repair (Blank group). Healing of the regenerated tissue and degeneration of the articular cartilage were evaluated by gross and histological analysis at postoperative weeks 1, 3, 6, and 12. The mechanical properties of the repaired meniscus were also analyzed (tensile testing).

Results

In vitro, magnesium promoted the adhesion and migration of SMSCs, which were identified and increased in the knee joints with meniscal lesions. Moreover, fibrochondrogenesis of SMSCs was stimulated by magnesium. Compared with the other groups, the Mg group had enhanced tissue regeneration, lower cartilage degeneration, and retained mechanical strength at 12 weeks after meniscal repair.

Conclusion

Magnesium could be used for in situ meniscal repair due to the potential capacity of magnesium to recruit endogenous stem cells and promote synthesis of fibrocartilaginous matrix. This study suggests the potential of magnesium in recruiting endogenous stem cells for in situ meniscal repair; however, this approach needs to be further investigated before being applied clinically.

Purpose

Meniscus injury and osteoarthritis are strongly correlated. The presence of multipotent mesenchymal stromal cells (MSCs) in different intra-articular tissues has been described. If progenitor cells are present in the meniscus, they could be targeted for meniscus tissue regeneration and used as a potential superior cell source for cell therapy. Therefore, the purpose of this study is to isolate and characterize meniscus-derived progenitor cells from osteoarthritic meniscus according to the MSC guidelines of the International Society for Cellular Therapy (ISCT).

Methods and Materials

Osteoarthritic menisci of 5 donors were digested to release the cells. Progenitor cells were selected by fibronectin adhesion and cultured up to passage 4. Trilineage potential of progenitor cells was compared to non-selected meniscus cells. After 3 weeks of culturing in differentiation medium, cells were stained with Alizarin red for osteogenic, Oil red O for adipogenic, and Safranin O for chondrogenic differentiation. Expression of positive (CD105, CD73 and CD90) and negative (CD45, CD34, CD11b, CD79A and HLA-DR) MSC markers was assessed by flow cytometry (n=2). Meniscus cells were co-cultured with progenitor cells in a 20:80 ratio in the absence of growth factors. Glycosaminoglycan and DNA content was determined using a dimethylmethylene-Blue (DMMB) and PicoGreen assay

Results

Both progenitor and meniscus cells demonstrated osteogenic and adipogenic differentiation. Progenitors showed glycosaminoglycan deposition, indicating chondrogenic differentiation. However, none of the meniscus cells showed chondrogenic differentiation. 73-87% of the progenitor cells expressed the surface marker profile according to the ISCT MSC-criteria. Co-culture of meniscus cells with progenitor cells increased glycosaminoglycan deposition.

Conclusion

Progenitor cells are present in osteoarthritic human meniscus. Progenitor cells have trilineage potential with higher chondrogenic capacity than non-selected meniscus cells. Moreover, meniscus progenitor cells express MSC markers. Co-culturing of progenitor and meniscus cells increases glycosaminoglycan deposition; therefore meniscus progenitor cells are a promising cell source for one-stage therapies and meniscus tissue engineering.