Polyurethane scaffold implants for partial meniscus lesions: delayed intervention leads to an inferior outcome.

PURPOSE: The purpose of this study was to assess the clinical outcomes of the implantation of an aliphatic polyurethane scaffold for the treatment of partial loss of meniscal tissue at a mean follow-up of 36 months. METHODS: A retrospective review on prospectively collected data was performed on patients who underwent implantation of an aliphatic polyurethane-based synthetic meniscal scaffold. Patients were evaluated for demographics data, lesion and implant characteristics (sizing, type and number of meniscal sutures), previous and combined surgeries and complications. Clinical parameters were rated using NRS, IKDC subjective, Lysholm, KOOS, and Tegner activity score, both preoperatively and at final follow-up. RESULTS: Sixty-seven patients were evaluated at a mean follow-up of 36 months (48 M and 19 F; mean age 40.8 ± 10.6 years; mean BMI 25.4 ± 4.3). The scaffold was implanted on the medial side in 54 cases, and on the lateral one in 13. Forty-seven patients had undergone previous surgical treatment at the same knee and 45 required combined surgical procedures. All evaluated scores improved significantly from the baseline. Among possible prognostic factors, a delayed scaffold implantation had lower post-operative clinical scores: IKDC subjective (P = 0.049), KOOS Sport (P = 0.044), KOOS total (p = 0.011), and Tegner (P = 0.03) scores at follow-up. CONCLUSIONS: The polyurethane meniscal scaffold implantation led to a significant clinical benefit in a large number of patients. A delayed intervention correlated with worse results. LEVEL OF EVIDENCE: IV.

SDF-1 preconditioned HPC scaffolds mobilize cartilage-derived progenitors and stimulate meniscal fibrocartilage repair in human explant tissue culture.

Purpose: The purpose of this study was to characterize the influence of SDF-1 on cell migration/adhesion and temporal gene expression of human cartilage mesenchymal progenitor cells (C-PCs); and to utilize SDF-1 conditioned mesenchymal progenitors to stimulate reintegration of human meniscus fibrocartilage breaks.Materials and Methods: Characterization of SDF-1-induced cell migration was achieved using hydroxypropyl cellulose (HPC) scaffolds pretreated with SDF-1. Fluorescence microscopy and cell counting were used to visualize and quantify the extent of cell migration into scaffolds, respectively. Relative mRNA expression analysis was used to characterize the temporal effects of SDF-1 on C-PCs. Tissue reintegration experiments were conducted using cylindrical human meniscal tissue punches, which were then placed back together with an HPC scaffold embedded with C-PCs. Tensile testing was used to evaluate the extent of tissue reintegration stimulated by human mesenchymal progenitors.Results: C-PCs migrate into scaffolds in response to SDF-1 with the same efficiency as mesenchymal progenitors from human marrow (BM-MSCs). SDF-1 treatment of C-PCs did not significantly alter the expression of early and late stage chondrogenic differentiation genes. Scaffolds containing SDF-1 pre-conditioned C-PCs successfully adhered to fibrocartilage breaks and migrated from the scaffold into the tissue. Tensile testing demonstrated that SDF-1 preconditioned C-PCs stimulate reintegration of fibrocartilage tears.Conclusion: C-PCs migrate in response to SDF-1. Exposure to SDF-1 does not significantly alter the unique mRNA profile of C-PCs that make them desirable for cartilaginous tissue repair applications. SDF-1 pretreated mesenchymal progenitors successfully disperse into injured tissues to help facilitate tissue reintegration.

Are the Biological and Biomechanical Properties of Meniscal Scaffolds Reflected in Clinical Practice? A Systematic Review of the Literature.

The aim of this PRISMA review was to assess whether the CMI and Actifit scaffolds, when used in clinical practice, improve clinical outcomes and demonstrate the ideal biological and biomechanical properties of scaffolds: being chondroprotective, porous, resorbable, able to mature and promote regeneration of tissue. This was done by only including studies that assessed clinical outcome and used a scale to assess both integrity of the scaffold and its effects on articular cartilage via MRI. A search was performed on PubMed, EMBASE, Scopus and clinicaltrials.gov. 2457 articles were screened, from which eight studies were selected: four used Actifit, three used CMI and one compared the two. All studies reported significant improvement in at least one clinical outcome compared to baseline. Some studies suggested that the scaffolds appeared to show porosity, mature, resorb and/or have possible chondroprotective effects, as assessed by MRI. The evidence for clinical translation is limited by differences in study methodology and small sample sizes, but is promising in terms of improving clinical outcomes in the short to mid-term. Higher level evidence, with MRI and histological evaluation of the scaffold and articular cartilage, is now needed to further determine whether these scaffolds exhibit these useful properties.

Weekly injections of Hylan G-F 20 delay cartilage degeneration in partial meniscectomized rat knees.

BACKGROUND: Cross-linked hyaluronan--also called Hylan G-F 20--is a medical device developed to treat osteoarthritis of the knee. However, it is still controversial whether Hylan G-F 20 has a cartilage protective effect in trauma-induced osteoarthritis. We investigated whether Hylan G-F 20 delayed osteoarthritis progression in a partial meniscectomized rat model. METHODS: Lewis rats were used for the experiments. The anterior medial meniscus was resected at the level of the medial collateral ligament in both knees. From 1 week after the surgery, 50 µl of Hylan G-F 20 was injected weekly into the left knee and phosphate buffered saline was injected into the right knee. Cartilage was evaluated for macroscopic findings, histology with safranin-o, and expression of type II collagen at 2, 4, and 8 weeks. Synovitis was also evaluated, and immunohistochemical analysis was performed for ED1. RESULTS: Macroscopic findings demonstrated that India ink positive area, representing fibrillated cartilage, was significantly smaller in the Hylan G-F 20 group than in the control group at 2, 4, and 8 weeks (n = 5). There were no significant differences in osteophyte score between the Hylan G-F 20 group and the control group at 2, 4, and 8 weeks. Histologically, the cartilage in the medial tibial plateau was destroyed at 8 weeks in the control group, while type II collagen expression was still observed at 8 weeks in the Hylan G-F 20 group. OARSI score for cartilage histology was significantly lower in the Hylan G-F 20 group than in the control group at 4 and 8 weeks (n = 5). There were no significant differences in synovial cell number or modified synovitis score between the Hylan G-F 20 group and the control group at 2, 4, and 8 weeks (n = 5). In the Hylan G-F 20 group, foreign bodies surrounded by ED1 positive macrophages were observed in the synovium. CONCLUSION: Weekly injections of Hylan G-F 20 starting 1 week after surgery delayed cartilage degeneration after meniscectomy in a rat model. Synovitis induced by meniscectomy was not alleviated by Hylan G-F 20. Insoluble gels were observed in the synovium after the Hylan G-F 20 injection.

A multilayer tissue engineered meniscus substitute.

Various methods have been tried to treat the main meniscus problem, meniscal tears, for which we believe tissue engineering could be a viable solution. In this study, a three dimensional, collagen-based meniscus substitute was prepared by tissue engineering using human fibrochondrocytes and a collagen based-scaffold. This construct was made with 3 different collagen-based foams interspaced with two electrospun nano/microfibrous mats. The top layer was made of collagen type I-chondroitin sulfate-hyaluronic acid (Coll-CS-HA), and the middle and the bottom layers were made of only collagen type I with different porosities and thus with different mechanical properties. The mats of aligned fibers were a blend of collagen type I and poly(L-lactic acid-co-glycolic acid) (PLGA). After seeding with human fibrochondrocytes, cell attachment, proliferation, and production of extracellular matrix and glucoseaminoglycan were studied. Cell seeding had a positive effect on the compressive properties of foams and the 3D construct. The 3D construct with all its 5 layers had better mechanical properties than the individual foams.

Frictional properties of the meniscus improve after scaffold-augmented repair of partial meniscectomy: a pilot study.

BACKGROUND: To prevent further degeneration, it is desirable to fill a meniscal defect with a supportive scaffold that mimics the mechanics of native tissue. Degradable porous scaffolds have been used, but it is unclear whether the tissue that fills the site of implantation is mechanically adequate, particularly with respect to frictional performance. QUESTIONS/PURPOSES: We therefore determined the frictional behavior of native and engineered meniscal replacement tissue from in vivo implantation over time. METHODS: We evaluated boundary and mixed-mode friction coefficients of tissue generated in porous polyurethane scaffolds used to augment the repair of the meniscus of 13 skeletally mature sheep after partial meniscectomy. Implants were removed for evaluation at 3, 6, and 12 months. The friction coefficient, aggregate modulus, and hydraulic permeability were evaluated for tissue harvested from native meniscus adjacent to the implants, native meniscus from the intact contralateral knee, and repair tissue from the site of the scaffold implantation. The equilibrium friction coefficient (µ(eq)) was measured in the presence of a lubricant bath of either phosphate-buffered saline (PBS) or equine synovial fluid (ESF). RESULTS: Boundary µ(eq) in PBS of engineered meniscus improved with time and was similar to native tissue after 6 months. ESF enhanced lubrication for all samples at nearly all time points demonstrating the efficacy of ESF as a joint lubricant for repair tissue as well as native meniscus. Modulus increased and permeability decreased with implantation, likely as a result of tissue ingrowth. CONCLUSIONS: Promoting tissue ingrowth into porous scaffolds is a potential strategy for improving friction performance in meniscal repair.

Changes in articular cartilage after meniscectomy and meniscus replacement using a biodegradable porous polymer implant.

PURPOSE: To evaluate the long-term effects of implantation of a biodegradable polymer meniscus implant on articular cartilage degeneration and compare this to articular cartilage degeneration after meniscectomy. METHODS: Porous polymer polycaprolacton-based polyurethane meniscus implants were implanted for 6 or 24 months in the lateral compartment of Beagle dog knees. Contralateral knees were meniscectomized, or left intact and served as controls. Articular cartilage degeneration was evaluated in detail using India ink staining, routine histology, immunochemistry for denatured (Col2-¾M) and cleaved (Col2-¾C(short)) type II collagen, Mankin's grading system, and cartilage thickness measurements. RESULTS: Histologically, fibrillation and substantial immunohistochemical staining for both denatured and cleaved type II collagen were found in all three treatment groups. The cartilage of the three groups showed identical degradation patterns. In the 24 months implant group, degradation appeared to be more severe when compared to the 6 months implant group and meniscectomy group. Significantly more cartilage damage (India ink staining, Mankin's grading system, and cartilage thickness measurements) was found in the 24 months implant group compared to the 6 months implant group and meniscectomy group. CONCLUSION: Degradation of the cartilage matrix was the result of both mechanical overloading as well as localized cell-mediated degradation. The degeneration patterns were highly variable between animals. Clinical application of a porous polymer implant for total meniscus replacement is not supported by this study.

Evaluation of a porous polyurethane scaffold in a partial meniscal defect ovine model.

PURPOSE: The objective of this study was to assess the performance of a degradable porous polyurethane scaffold in a partial meniscectomy ovine model. METHODS: We subjected 42 skeletally mature ewes to unilateral partial excision of the lateral meniscus. In 19 animals the defect was left unfilled; in 23 animals a scaffold was inserted. Knees were examined by magnetic resonance imaging, gross inspection, and histologic inspection of the cartilage of the tibial plateau. RESULTS: In contrast to what has been previously reported in a complete meniscal replacement model, cartilage damage did not occur under the site of scaffold implantation; this was likely influenced by the rapid infiltration of cells and the dense tissue that formed within the scaffold. Cartilage damage in both groups was located close to the midline of the joint. No significant difference in the condition of the articular cartilage of the tibial plateau was seen between groups up to 12 months postoperatively. This result was influenced by the fact that the partly meniscectomized knees also showed unexpected tissue regeneration within the defect site, which raises concern about the suitability of using a partial meniscectomy as a control in the ovine model. CONCLUSIONS: Our study has shown that implantation of a polyurethane scaffold in a partial meniscectomy ovine model promotes tissue ingrowth without damaging the cartilage with which it articulates. CLINICAL RELEVANCE: Meniscal deficiency is a common occurrence, the effective clinical management of which is limited by the absence of an off-the-shelf implantable construct.

Treating human meniscal fibrochondrocytes with hIGF-1 gene by liposome.

The menisci are intraarticular fibrocartilaginous structures essential to the normal function of the knee that lack the ability to self-repair. Human meniscal fibrochondrocytes may respond to beneficial genes like human insulin growth factor-1 (hIGF-1) and the meniscal cell may be a feasible donor for gene therapy. To explore this possibility, we amplified the hIGF-1 gene sequence in full length and cloned it into a bicistronic plasmid. This gene was then transfected into cultured human meniscal fibrochondrocytes by the liposome FuGene 6. Green fluorescence was expressed in part of the cells 6 hours after transfection and increased gradually, with a peak concentration of the hIGF-1 in the supernatants to 22.68 ng/mL 56 hours after transfection. Phenotypes of some cells changed and the proliferation accelerated after transfection. Flow cytometry analysis demonstrated upregulation of cell numbers in the G2 and S stages after hIGF-1 gene introduction. We conclude the hIGF-1 gene can be transfected into the human meniscal cell efficiently by liposome and it causes accelerated proliferation and differentiation. Within 10 days after transfection, the cytokine appears to be secreted into supernatants with the bioactivity and promotes the proliferation of the NIH 3T3 cell line.

Enhanced meniscal repair by overexpression of hIGF-1 in a full-thickness model.

The importance of the menisci to the well-being of the normal knee is well-documented. However, there is no ideal repair or reconstructive approach for damaged menisci. Gene therapy provides one promising alternative strategy, especially when combined with injectable tissue engineering to achieve minimally invasive clinical application. We asked whether the introduction of human insulin-like growth factor 1 (hIGF-1) gene could improve the repair of full-thickness meniscal defects. We created full-thickness meniscal defects in the "white area" of the anterior horn in 48 goats. Bone marrow stromal cells with the transfection of hIGF-1 gene and injectable calcium alginate gel were mixed together to repair the defects; three control groups included cells without transfection, gel without cells, and defects left empty. After 4, 8, and 16 weeks, the animals were euthanized and the excised defects were examined by macroscopic assessment, histological analysis, electron microscopy, proteoglycan determination, and MRI. Sixteen weeks after surgery the repaired meniscal defects were filled with white tissue similar to that in normal meniscal fibrocartilage. The repair tissue was composed of cells embedded within matrix that filled the spaces of the fibers. The proteoglycan content in the gene-enhanced tissue engineering group was higher than those in the control groups, and less than that in the normal meniscus. The results suggest full-thickness meniscal defects in regions without blood supply can be reconstructed with hIGF-1-enhanced injectable tissue engineering.

Healing of meniscal tissue by cellular fibrin glue: an in vivo study.

Menisci represent fundamental structures for the maintenance of knee homeostasis, playing a key role in knee biomechanics. However, their intrinsic regenerative potential is poor. As a consequence, when a lesion occurs and the meniscus is partially removed by surgery, knee mechanics is subject to dramatic changes. These have been demonstrated to lead often to the development of early osteoarthritis. Therefore, menisci should be repaired whenever possible. In the last decades, tissue engineering approaches have been advocated to improve the reparative processes of joint tissues. In this study, the bonding capacity of an articular chondrocytes-fibrin glue hydrogel was tested as a biologic glue to improve the bonding between two swine meniscal slices in a nude mouse model. The composites were wrapped with acellular fibrin glue and implanted in subcutaneous pouches of nude mice for 4 weeks. Upon retrieval, a firm gross bonding was observed in the experimental samples while none of the control samples, prepared with acellular fibrin glue at the interface, presented any sign of bonding. This was consistent with the histological and scanning electron microscope findings. In particular, a fibrocartilaginous tissue was found at the interface between the meniscal slices, partially penetrating the native meniscus tissue. In order to overcome the lack of regenerative properties of the meniscus, the rationale of using cellular fibrin glue is that fibrin provides immediate stability while carrying cells in the site of lesion. Moreover, fibrin gel is recognized as an optimal scaffold for cell embedding and for promoting fibrocartilaginous differentiation of the cells which synthesize matrix having healing property. These results demonstrated the potential of this model for improving the meniscal bonding. However, further orthotopic studies in a large animal model are needed to evaluate its potential for clinical application.

[Analysis of degradation failure of poly L-lactic acid fixators used in meniscus tears]. / Menisküs yirtiklarinin atroskopik tamirinde kullanilan poli L-laktik asit sabitleyicilerin erimeme nedenlerinin arastirilmasi.

OBJECTIVES: Biodegradable poly L-lactic acid (PLLA) fixators used in the repair of meniscal tears may cause adverse reactions inside the knee due to delayed degradation. This study was designed to determine the reasons for late degradation of PLLA fixators. METHODS: Three unused and three used meniscal PLLA fixators (BioStinger) were analyzed. The latter were removed from three patients due to persisting symptoms within six months after knee arthroscopy. Fourier transform infrared (FTIR) spectroscopy was performed and external and internal surfaces of the samples were examined by scanning electron microscopy (SEM) and X-ray fluoroscopy (XRF). Chemical structural analyses of two samples (one from each group) were made by 1H-nuclear magnetic resonance (1H-NMR) spectroscopy. Degradation times of two samples (one from each group) by oxidative hydrolysis in hydrogen peroxide solution were recorded. RESULTS: Chemical structure of used and unused fixators did not differ in FTIR analysis. With increasing temperatures, unused and used fixators showed degradation with and without melt flow, respectively. In SEM analysis, inner sections of unused fixators were homogeneous, whereas those of the used ones exhibited crystals which were found to be sodium and potassium chloride salts in XRF analysis. The 1H-NMR spectrum of used and unused samples showed the normal pattern of lactic acid polymer. The unused and used fixators degraded in hydrogen peroxide solution in 10 days and 30 days, respectively. CONCLUSION: Both fixators had the same chemical structure in FTIR and NMR analyses. Formation of salt crystals seemed to be the most important cause of degradation failure, while changes in the physical properties of fixators were thought to be associated with delayed degradation.

In Vivo Performance of a Novel, Anatomically Shaped, Total Meniscal Prosthesis Made of Polycarbonate Urethane: A 12-Month Evaluation in Goats.

BACKGROUND: Injury or loss of the meniscus generally leads to degenerative osteoarthritic changes in the knee joint. However, the treatment options for symptomatic patients with total meniscectomy are limited. Therefore, we developed a novel, anatomically shaped, total meniscal implant made of polycarbonate urethane. PURPOSE: To evaluate the in vivo performance of this novel total meniscal implant. The assessment particularly focused on the implant's response to long-term physiological loading in a goat model and its chondroprotective capacity in comparison to clinically relevant controls. STUDY DESIGN: Controlled laboratory study. METHODS: Surgery was performed to the stifle joint of 26 female Saanen goats, subdivided into 4 groups: implant, allograft, total meniscectomy, and sham surgery. The sham group's contralateral joints served as nonoperated controls. After 12 months of follow-up, investigators evaluated implant wear, deformation, and the histopathological condition of the synovium and cartilage. RESULTS: Wear of the implant's articulating surfaces was minimal, which was confirmed by the absence of wear particles in the synovial fluid. Implant deformation was limited. However, one implant failed by complete tearing of the posterior horn extension. No differences in cartilage histopathological condition were observed for the implant, allograft, and meniscectomy groups. However, locally, the cartilage scores for these groups were significantly worse than those of the nonoperated controls. CONCLUSION: Whereas this study demonstrated that the novel implant is resistant to wear and that deformation after 12 months of physiological loading is acceptable, reinforcement of the implant horns is necessary to prevent horn failure. Although the implant could not protect the cartilage from developing degenerative changes, the progression of damage was similar in the allograft group. CLINICAL RELEVANCE: This novel polycarbonate urethane implant may have the potential to become an alternative treatment for symptomatic patients with total meniscectomy.

Effect of lesion location on fixation strength of the meniscal viper repair system: an in vitro study using porcine menisci.

PURPOSE: The Meniscal Viper Repair System (Arthrex, Naples, FL) is a novel suture-based all-inside meniscal repair system. This study was performed to test whether the Meniscal Viper Repair System would provide superior fixation characteristics for vertical longitudinal meniscal lesions located closer to the periphery compared with those located further away from the periphery. METHODS: Vertical longitudinal lesions were created either 1 to 2 mm or 3 to 4 mm away from the periphery of porcine menisci. After repair with the Meniscal Viper Repair System, fixation characteristics were studied during cyclic (500 cycles, 5 to 50 N) and load to failure testing (5 mm/min) in a servo hydraulic device. RESULTS: Meniscal lesion repair location did not show significant differences in displacement or stiffness during cyclic testing. During load to failure testing, meniscal lesion repairs located 1 to 2 mm from the periphery showed superior load at failure (188.8 +/- 45.4 N) compared with repairs located 3 to 4 mm from the periphery (114.4 +/- 35.0 N) (P = .01). Stiffness and displacement during load to failure testing did not show statistically significant differences. CONCLUSIONS: The Meniscal Viper Repair System provides stronger meniscal repair strength when lesions are located within 1 to 2 mm of the periphery. CLINICAL RELEVANCE: The Meniscal Viper Repair System is better suited for repair of peripheral meniscal lesions located within 1 to 2 mm of the periphery. For lesions located in zone 2 (within the central 50%), careful assessment of their distance from the periphery is recommended. For lesions located more than 3 to 4 mm away from the periphery, alternative repair systems or augmentation with other devices may be prudent.

Midterm results of meniscal repair using the BioStinger meniscal repair device.

PURPOSE: The purpose of this study was to evaluate the midterm healing rate and any adverse events from meniscus repair using the BioStinger meniscus repair device (Linvatec, Largo, FL). METHODS: A retrospective review of a consecutive series of meniscal repairs performed by a single surgeon using the BioStinger was conducted. The BioStinger is cannulated, made of molded poly L-lactic acid, and inserted over a needle into the meniscus tissue. Clinical results and adverse events were noted, and Lysholm, Tegner, Cincinnati, and International Knee Documentation Committee (IKDC) activity scores were obtained on all patients. RESULTS: Forty-one patients underwent 41 meniscal repairs with an average follow-up of 38.6 months (range, 24 to 69 months); 35 meniscus repairs were performed in conjunction with anterior cruciate ligament reconstruction and 6 in stable knees. Tears repaired were peripheral, posterior horn tears with an average length of 2 cm. Clinical evidence of meniscal healing was observed in 95% at the time of last follow-up. Six second-look arthroscopies were performed and 2 failures were found. All other patients were symptom free. At follow-up, the mean Tegner score was 6.1 (2.8 preoperative), IKDC activity score was 3.3 (2.1 preoperative), Lysholm score was 90.6 (48.7 preoperative), and the mean Cincinnati score was 86.7 (41.3 preoperative). Four patients had peripheral migration of the device without skin tenting or perforation; 3 underwent removal of the BioStinger from the soft tissues and the other resolved after 12 months. CONCLUSIONS: The midterm clinical success rate was 95% using the BioStinger device. Adverse events were observed in few cases. LEVEL OF EVIDENCE: Level IV, cases series.

Development of biodegradable hyper-branched tissue adhesives for the repair of meniscus tears.

Meniscus tears are one of the most commonly occurring injuries of the knee joint. Current meniscus repair techniques are challenging and do not bring fully satisfactory results. Tissue adhesives are a promising alternative, since they are easy to apply and cause minimal tissue trauma. In this study, a series of amphiphilic copolymers based on polyethylene glycol, trimethylene carbonate and citric acid were synthesized and subsequently end-functionalized with hexamethylene diisocyanate to form reactive adhesive materials. The shear adhesive strength of the networks to bovine meniscus tissue measured in a lap-shear adhesion test ranged between 20 and 80 kPa, which was better than for fibrin glue (10 kPa). The elastic modulus of the networks depended on composition and was in the same range as that of human meniscus. Cell compatibility was assessed using Alamar Blue staining after incubation of the bovine meniscus cells with different concentrations of the glues for 7 days. Cell viability was not affected after adding up to 3mg of the adhesive/mL of medium. The proposed materials are suitable candidates to be used as resorbable tissue adhesives for meniscus repair. They have excellent mechanical and adhesive properties that can be adjusted by varying the composition of the copolymers. STATEMENT OF SIGNIFICANCE: Meniscal tears often occur and current treatment strategies do not bring fully satisfactory results. Use of biodegradable tissue adhesives would be an interesting option, but currently available adhesives are not suited due to toxicity or poor mechanical properties. Here, we describe the development of novel biodegradable, hyper-branched, adhesive copolymers. These adhesives cure upon contact with water forming flexible networks. Their adhesion to bovine meniscus tissue was significantly better than that of clinically used fibrin glue. The tensile properties of the cured networks were in the same range of values of the human meniscus. When physiologically relevant amounts were added to cells in culture, not toxic effects were observed. Therefore, the proposed materials are interesting resorbable tissue adhesives for meniscus repair.

Short Term Evaluation of an Anatomically Shaped Polycarbonate Urethane Total Meniscus Replacement in a Goat Model.

PURPOSE: Since the treatment options for symptomatic total meniscectomy patients are still limited, an anatomically shaped, polycarbonate urethane (PCU), total meniscus replacement was developed. This study evaluates the in vivo performance of the implant in a goat model, with a specific focus on the implant location in the joint, geometrical integrity of the implant and the effect of the implant on synovial membrane and articular cartilage histopathological condition. METHODS: The right medial meniscus of seven Saanen goats was replaced by the implant. Sham surgery (transection of the MCL, arthrotomy and MCL suturing) was performed in six animals. The contralateral knee joints of both groups served as control groups. After three months follow-up the following aspects of implant performance were evaluated: implant position, implant deformation and the histopathological condition of the synovium and cartilage. RESULTS: Implant geometry was well maintained during the three month implantation period. No signs of PCU wear were found and the implant did not induce an inflammatory response in the knee joint. In all animals, implant fixation was compromised due to suture breakage, wear or elongation, likely causing the increase in extrusion observed in the implant group. Both the femoral cartilage and tibial cartilage in direct contact with the implant showed increased damage compared to the sham and sham-control groups. CONCLUSION: This study demonstrates that the novel, anatomically shaped PCU total meniscal replacement is biocompatible and resistant to three months of physiological loading. Failure of the fixation sutures may have increased implant mobility, which probably induced implant extrusion and potentially stimulated cartilage degeneration. Evidently, redesigning the fixation method is necessary. Future animal studies should evaluate the improved fixation method and compare implant performance to current treatment standards, such as allografts.

Engineering meniscus structure and function via multi-layered mesenchymal stem cell-seeded nanofibrous scaffolds.

Despite advances in tissue engineering for the knee meniscus, it remains a challenge to match the complex macroscopic and microscopic structural features of native tissue, including the circumferentially and radially aligned collagen bundles essential for mechanical function. To mimic this structural hierarchy, this study developed multi-lamellar mesenchymal stem cell (MSC)-seeded nanofibrous constructs. Bovine MSCs were seeded onto nanofibrous scaffolds comprised of poly(ε-caprolactone) with fibers aligned in a single direction (0° or 90° to the scaffold long axis) or circumferentially aligned (C). Multi-layer groups (0°/0°/0°, 90°/90°/90°, 0°/90°/0°, 90°/0°/90°, and C/C/C) were created and cultured for a total of 6 weeks under conditions favoring fibrocartilaginous tissue formation. Tensile testing showed that 0° and C single layer constructs had stiffness values several fold higher than 90° constructs. For multi-layer groups, the stiffness of 0°/0°/0° constructs was higher than all other groups, while 90°/90°/90° constructs had the lowest values. Data for collagen content showed a general positive interactive effect for multi-layers relative to single layer constructs, while a positive interaction for stiffness was found only for the C/C/C group. Collagen content and cell infiltration occurred independent of scaffold alignment, and newly formed collagenous matrix followed the scaffold fiber direction. Structural hierarchies within multi-lamellar constructs dictated biomechanical properties, and only the C/C/C constructs with non-orthogonal alignment within layers featured positive mechanical reinforcement as a consequence of the layered construction. These multi-layer constructs may serve as functional substitutes for the meniscus as well as test beds to understand the complex mechanical principles that enable meniscus function.

Animal models for meniscus repair and regeneration.

The meniscus plays an important role in knee function and mechanics. Meniscal lesions, however, are common phenomena and this tissue is not able to achieve spontaneous successful repair, particularly in the inner avascular zone. Several animal models have been studied and proposed for testing different reparative approaches, as well as for studying regenerative methods aiming to restore the original shape and function of this structure. This review summarizes the gross anatomy, function, ultrastructure and biochemical composition of the knee meniscus in several animal models in comparison with the human meniscus. The relevance of the models is discussed from the point of view of basic research as well as of clinical translation for meniscal repair, substitution and regeneration. Finally, the advantages and disadvantages of each model for various research directions are critically discussed.

A new method for meniscus repair using type I collagen scaffold and infrapatellar fat pad.

AIM: The aim of this study was to investigate a new method for meniscal repair by combinative transplantation with type I collagen scaffold and infrapatellar fat pad. METHODS: Two-mm cylindrical defects at the anterior part of bilateral medial menisci were prepared in nine Japanese white rabbits. The 18 knees were equally divided into three groups: I, no treatment; II, collagen scaffold transplantation; and III, collagen scaffold and infrapatellar fat pad transplantation. Another three rabbits (six knees) underwent sham surgery and served as controls. Rabbits were sacrificed at eight weeks after transplantation. Surface area of the medial meniscus was evaluated using macrophotographs. Ishida score for meniscal regeneration was used for assessment. To evaluate the composition of regenerated tissue, immunohistochemistry was analyzed with anti-type I and anti-type II collagen antibodies, and anti-Ki67 antibody. To investigate the effects of collagen scaffold on human meniscus, cells were isolated from human meniscus and infrapatellar fat pad, and cultured with collagen scaffold for three weeks. After that, gene expression was evaluated by using quantitative real-time polymerase chain reaction. RESULTS: In group I, the meniscus shrank anterior to posterior, and the surface area was significantly less than that of normal meniscus. However, the surface area was maintained in group III. Ishida score and Ki67-positive cell ratio in group III were significantly higher than that in any other group, and staining with type I and type II collagen was similar to that of the control. Expression of matrix metalloproteinase was significantly lower in cocultures of collagen scaffold, meniscus cell, and infrapatellar fat pad cell than in monocultured meniscus cell, and expression of interleukin-1ß was not increased. CONCLUSION: This new method for meniscal repair by combinative transplantation with type I collagen scaffold and infrapatellar fat pad showed meniscal regeneration and potential for suppressing inflammation.