Meniscal Defects Research Articles

Healthy but not osteoarthritic human meniscus-derived matrix scaffolds promote meniscus repair.

Meniscus tissue is commonly injured due to sports-related injuries and age-related degeneration and approximately 50% of individuals with a meniscus tear will develop post-traumatic osteoarthritis (PTOA). Given that the meniscus has limited healing potential, new therapeutic strategies are required to enhance meniscus repair. Porcine meniscus-derived matrix (MDM) scaffolds improve meniscus integrative repair, but sources of human meniscus tissue have not been investigated. Therefore, the objectives of this study were to generate healthy and osteoarthritic (OA) MDM scaffolds and to compare meniscus cellular responses and integrative repair. Meniscus cells showed high viability on both healthy and OA scaffolds. While DNA content was higher in cell-seeded OA scaffolds than cell-seeded healthy scaffolds, CCK-8, and both sGAG and collagen content were similar between scaffold types. After 28days in an ex vivo meniscus defect model, healthy and OA scaffolds had similar DNA, sGAG, and collagen content. However, the shear strength of repair was reduced in defects containing OA scaffolds compared to healthy scaffolds. In conclusion, healthy human allograft tissue is a useful source for generating MDM scaffolds that can support cellular growth, ECM production, and ex vivo integrative repair of the meniscus, highlighting the potential suitability for tissue engineering approaches to improve meniscus repair.

Development of a novel approach for restoration of the meniscus using silk-elastin in a rabbit meniscus injury model

BackgroundLimited healing potential of the meniscus remains a burden for the successful repair of meniscus injuries in the orthopaedic fields. Silk-elastin (SE) is a novel recombinant protein with favorable properties for wound healing. This proof-of-concept study aimed to investigate the therapeutic effect of silk-elastin in a rabbit meniscal defect model.MethodsA migration assay using rabbit meniscus and synovial cells with various concentrations of SE in a culture medium was conducted to investigate the mechanism of meniscal healing by SE. Additionally, cylindrical defects with a 1.5 mm diameter were created at the anterior horn of the medial meniscus of rabbits. The animals were divided into three groups: 1) the Blank group; defect only, 2) the Col I group; implantation of type I atelocollagen sponge, and 3) the SE group; implantation of SE (150 mg/ml) sponge. Whole medial menisci were harvested at 4, 8, 12, and 24 weeks after surgery. Histological analyses including immunohistochemical staining were performed to assess meniscal healing.ResultsIn vitro study, Migration assay demonstrated a significantly higher number of migrated cells only in synovial cells. Especially, the SE concentration of 10 µg/mL demonstrated the highest number of migrated cells compared with other concentrations. In vivo study, the SE group exhibited significantly higher Ishida scores than other groups at all time points. Furthermore, the SE group showed higher synovial coverage scores than the Col I group at 4 and 8 weeks. Immunohistochemical staining demonstrated higher type II collagen staining in the SE group compared to other groups at 12 weeks. Implanted SE was efficiently replaced by safranin-O staining positive tissue within 8 weeks.ConclusionsSE could effectively repair a meniscal defect by inducing coverage of synovial cells. SE has the potential to be a useful material for meniscal repair.

Magnetic resonance imaging combined with histological evaluation of repair process using the microfracture technique in an association of osteocartilaginous and meniscal surgically induced lesions of the knee. In vivo experiment on a rabbit model.

The present research study aimed to assess magnetic resonance imaging (MRI) changes and histological findings in the therapeutic effects of microfractures in the treatment of complex animal knee lesions resulting from osteochondral and meniscal defects resulting from non-total meniscectomies. The anterior cruciate ligament lesions are also proven to facilitate the development of osteoarthritis in the knee and worsen the prognosis. Surgery was performed on the right knee joint of 22 male rabbits in order to partially remove the anterior horn of the internal meniscus and to induce an osteochondral defect at the level of the internal femoral condyle. The induced lesion complex was aimed to simulate a clinical situation that occurs frequently in orthopedic practice when young adults undergo partial meniscectomy and at the time of surgery, an osteochondral defect is diagnosed. Rabbits were separated into two study groups: the control (C1) group and the microfractures (MF2) group. After the induced cartilage defect and partial meniscectomy, both groups were followed-up for six months using detailed MRI. Also, anatomical specimens were histologically analyzed to show modifications and signs of healing process, along with complications, in the study group. The results showed that the microfracture group had better results concerning articular surface defect healing in comparison to the control group. Our results suggest that microfractures do improve results concerning surface contact healing and serial MRI studies can be useful in observing the remodeling process in dynamics.

Photo-Polymerizable Autologous Growth-Factor Loaded Silk-Based Biomaterial-Inks toward 3D Printing-Based Regeneration of Meniscus Tears.

Meniscustears in the avascular region undergoing partial or full meniscectomy lead to knee osteoarthritis and concurrent lifestyle hindrances in the young and aged alike. Here they reported ingenious photo-polymerizable autologous growth factor loaded 3D printed scaffolds to potentially treat meniscal defects . A shear-thinning photo-crosslinkable silk fibroin methacrylate-gelatin methacrylate-polyethylene glycol dimethacrylate biomaterial-ink is formulated and loaded with freeze-dried growth factor rich plasma (GFRP) . The biomaterial-ink exhibits optimal rheological properties and shape fidelity for 3D printing. Initial evaluation revealed that the 3D printed scaffolds mimicmechanical characteristics of meniscus, possess favourable porosity and swelling characteristics, and demonstrate sustained GFRP release. GFRP laden 3D scaffolds are screened with human neo-natal stem cells in vitro and biomaterial-ink comprising of 25mg mL-1 of GFRP (GFRP25) is found to be amicable for meniscus tissue engineering. GFRP25 ink demonstratedrigorous rheological compliance, and printed constructs demonstrated long term degradability (>6 weeks), GFRP release (>5 weeks), and mechanical durability (3 weeks). GFRP25 scaffolds aided in proliferation of seeded human neo-natal stem cellsandtheir meniscus-specific fibrochondrogenic differentiation . GFRP25 constructs show amenable inflammatory response in vitro and in vivo. GFRP25 biomaterial-ink and printed GFRP25 scaffolds could be potential patient-specific treatment modalities for meniscal defects.

Mechano Growth Factor E Peptide Improves Degenerative Meniscus by Promoting the Proliferation and Migration of Meniscus Cells

This study aimed to examine the effect of the Mechano growth factor E peptide on meniscus repair, which is critical for restoring knee joint function. Meniscal cells harvested from the inner and outer regions of knee joints from patients with osteoarthritis were subjected to Mechano growth factor E peptide treatment to investigate alterations in cell morphology and their effect on cell colony formation. The effect of Mechano growth factor E peptide treatment on cell migration was evaluated using a transwell system, while polymerase chain reaction was utilized to assess the effect of Mechano growth factor E peptide treatment on the mRNA expression level of COL1A1 or COL2A1, which encode for key collagen types. The reparative effect of the Mechano growth factor E peptide on the meniscus was evaluated using a rabbit meniscal defect model and complemented with hematoxylin and eosin staining. We found that Mechano growth factor E peptide administration augments meniscal cell proliferation, migration, and collagen synthesis, thereby enhancing in vivo meniscus repair. This study examined the capacity of the Mechano growth factor E peptide to ameliorate meniscal injury by promoting meniscal cell proliferation and migration.

Loss of chondroprotection of medial collagen meniscus implant (CMI) at 20-year follow-up

ObjectiveThe mid-term results of the collagen meniscus implant (CMI) procedure for the replacement of partial meniscus defects have already been described. However, there is a paucity of long-term comparative studies. This study aimed to compare the clinical outcomes, failures, and osteoarthritis progression of patients who underwent partial medial meniscectomy and medial CMI implantation. MethodsThirty-six nonconsecutive patients with medial meniscus injuries that underwent medial CMI (MCMI) implantation or partial medial meniscectomy (PMM) between 1997 and 2000 were included in a prospective study with an intermediate 10-year follow-up examination and a final follow-up examination at 20-year follow-up. Outcome measures at the 20-year follow-up included the Lysholm score, visual analogue scale (VAS) for pain, International Knee Documentation Committee (IKDC) knee form , and Tegner activity level. Bilateral weight-bearing radiographs were also performed to evaluate hip-knee-angle (HKA) and the medial joint line height (JL). Data regarding complications and failures were also collected. ResultsAt the 20-year follow-up, 31 patients (83% follow-up rate) with a mean age of 60.7 ​± ​8.9 years were included in the final analysis (21.1 ​± ​1.2 years follow-up). Four reoperations and one failure per group were reported. When comparing the clinical results of the two groups, no difference was found considering the Lysholm score, Knee Injury and Osteoarthritis Outcome Score (KOOS), Tegner, and the IKDC. Moreover, 20 patients underwent radiographic examination (10 MCMI, 10 ​MM), and no statistically significant difference was reported concerning the JL, HKA, and the presence and incidence of osteoarthritis between the two groups. ConclusionThe CMI implant for partial medial meniscectomy provided good long-term results and a low failure rate. However, differently from the 10 years follow-up, the clinical and the radiological outcomes were not superior compared to the medial meniscectomy group. The present study's result suggests that using a medial scaffold is not chondroprotective. Level of evidenceIII, Prospective case–control study.

Arthroscopic All-Suture Anchor Technique for Unstable Ramp Lesions with Medial Meniscal Defects

A ramp lesion is a specific type of tear in the meniscocapsular junction of the posterior horn of the medial meniscus, usually associated with anterior cruciate ligament (ACL) injury. Biomechanical cadaveric studies have shown that ACL injury combined with ramp lesions significantly increases anterior tibial translation and external rotation, which ACL reconstruction alone cannot completely control. Additionally, ramp lesions are sometimes associated with medial meniscal defects, especially in cases of chronic ACL deficiency after repetitive traumatic events, in which the anatomical repair of the meniscocapsular junction is infeasible. This report describes a new arthroscopic repair technique using an all-suture anchor through a posteromedial portal for unstable ramp lesions with medial meniscal defects.

Fibronectin-coated polyurethane meniscal scaffolding supplemented with MSCs improves scaffold integration and proteoglycan production in a rabbit model.

The role of mesenchymal stem cells (MSC) in supporting the formation of new meniscal tissue in a meniscal scaffold is not well understood. The objective of this study was to assess the quality of the meniscal tissue produced in a fibronectin (FN)-coated polyurethane (PU) meniscal scaffold after a meniscal injury was made in an experimental rabbit model. Twelve New Zealand white rabbits were divided in two groups after performing a medial meniscectomy of the anterior horn. In group 1, the meniscal defect was reconstructed with a non-MSC supplemented FN-coated PU scaffold. On the other hand, the same scaffold supplemented with MSCs was used in group 2. The animals were sacrificed at 12week after index surgery. A modified scoring system was used for histological assessment. This new scoring (ranging from 0 to 15) includes a structural evaluation (meniscal scaffold interface and extracellular matrix production) and tissue quality evaluation (proteoglycan and type I-collagen content). The meniscal scaffold was found loose in the joint in three cases, corresponding to two cases in group 1 and 1 case in group 2. No differences were observed between the groups in terms of the total score (7.0 ± 0.9 vs. 9.4 ± 2.6, p = 0.09). However, differences were observed in group 2 in which 2 out of the 5 scored items, scaffold integration (1 ± 0.0 vs. 1.9 ± 0.6, p = 0.03) and proteoglycan production (1.2 ± 0.3 vs. 2.4 ± 0.2, p = 0.001). A trend to a higher production of Type I-Collagen production was also observed in group 2 (1.1 ± 0.4 vs. 1.4 ± 0.7, p = 0.05). In a rabbit model at 12weeks, the adhesion of MSCs to a FN-coated PU scaffold improves scaffold integration, proteoglycan production and the characteristics of the new meniscal-like tissue obtained when compared to a non-supplemented scaffold. This fact could be a major step toward improving the adhesion of the MSCs to meniscal scaffolds and, consequently, the obtention of better quality meniscal tissue.

Basic fibroblast growth factor promotes meniscus regeneration through the cultivation of synovial mesenchymal stem cells via the CXCL6–CXCR2 pathway

To investigate the efficacy of basic fibroblast growth factor (bFGF) in promoting meniscus regeneration by cultivating synovial mesenchymal stem cells (SMSCs) and to validate the underlying mechanisms. Human SMSCs were collected from patients with osteoarthritis. Eight-week-old nude rats underwent hemi-meniscectomy, and SMSCs in pellet form, either with or without bFGF (1.0×106 cells per pellet), were implanted at the site of meniscus defects. Rats were divided into the control (no transplantation), FGF (-) (pellet without bFGF), and FGF (+) (pellet with bFGF) groups. Different examinations, including assessment of the regenerated meniscus area, histological scoring of the regenerated meniscus and cartilage, meniscus indentation test, and immunohistochemistry analysis, were performed at 4 and 8 weeks after surgery. Transplanted SMSCs adhered to the regenerative meniscus. Compared with the control group, the FGF (+) group had larger regenerated meniscus areas, superior histological scores of the meniscus and cartilage, and better meniscus mechanical properties. RNA sequencing of SMSCs revealed that the gene expression of chemokines that bind to CXCR2 was upregulated by bFGF. Furthermore, conditioned medium derived from SMSCs cultivated with bFGF exhibited enhanced cell migration, proliferation, and chondrogenic differentiation, which were specifically inhibited by CXCR2 or CXCL6 inhibitors. SMSCs cultured with bFGF promoted the expression of CXCL6. This mechanism may enhance cell migration, proliferation, and chondrogenic differentiation, thereby resulting in superior meniscus regeneration and cartilage preservation.

Poster 136: Augmented Meniscus Radial Tear Healing via Local Transforming Growth Factor-beta 1 (TGF- β1) Gene Therapy in a Rat Model

Objectives: Meniscus tears cause significant musculoskeletal impairment and are among the most common knee injuries. Tears in the inner third of the meniscus have intrinsically poor healing capacity due to insufficient blood supply. In an effort to improve healing, use of biologic augments is a promising area of investigation. Tissue engineering strategies, such as growth factor gene therapy, have emerged as encouraging approaches to improving meniscal healing. Transforming Growth Factor-Beta 1 (TGF-β1) gene therapy has shown promise in vitro and ex vivo as a therapeutic strategy, but its effects on meniscus healing in vivo remain unknown. This study aimed to determine whether local delivery of viral vectors carrying the TGF-β1 gene could improve the healing of a meniscus tear involving the avascular zone in vivo in a rat model. Methods: Recombinant adenoviruses were generated using the AdEasy system. Briefly, the coding regions of mouse TGFβ1 were PCR amplified and cloned into an adenoviral shuttle vector and subsequently used to generate recombinant adenoviruses in HEK293 cells. The resulting adenoviruses were designated as Adv-TGF-β1. An analogous adenovirus expressing only GFP (Adv-GFP) was used as mock virus controls. To achieve local delivery of viral vectors to the injury site, we utilized a thermoresponsive biodegradable polydiolcitrate-gelatin delivery scaffold (PPCNg). A full-thickness radial tear was made in the medial meniscus of the left hind leg of twelve Wistar rats. Rats were divided into two groups: one receiving a mixture of PPCNg+TGF-β1 (n = 3) and the other receiving PPCNg+GFP (n = 3). A 4ºC pre-chilled solution of PPCNg seeded with Adv-TGF-β1 or Adv-GFP at 1011 infectious viral particles/injection was administered at the site of the induced meniscus tear. After 3 weeks, rats were euthanized, and the menisci were histologically evaluated by hematoxylin and eosin (H&E) staining. The histologic assessment and scoring of meniscus tissue wound healing were done by one blinded and one unblinded observer, each using selected wound healing parameters as described in Table 1, and the results were averaged. The intra-class correlation coefficient (ICC) was computed based on a mean rating (k=2), absolute agreement, and two-way random effects model to assess the agreement between the wound healing score rating of the two observers. Statistical significance between groups was determined using the Mann-Whitney Wilcoxon rank sum test. A value of p < 0.05 was considered statistically significant. All animal procedures were performed according to an Institutional Animal Care and Use Committee protocol at the home institution. Results: Immediately after and 3 weeks post-surgery, there was no evidence of infection, dehiscence, or functional deficit. Histologic evaluation of the sections (n = 8/group) of harvested rat menisci (n = 2/group) revealed improved healing of tears in the PPCNg+TGF-β1 group compared to the control group (5.7 ± 0.48 vs. 5.0 ± 0.89, p = 0.011) (Figure 1B). The lesion area demonstrated significantly greater neovascularization (2.75 ± 0.45 vs. 2.06 ± 0.68, p = 0.004), better collagen organization (1.94 ± 0.25 vs. 1.62 ± 0.50, p = 0.038), and increased hypercellularity (1.0 ± 0.00 vs. 1.3 ± 0.48, p = 0.018) in the PPCNg+TGF-β1 group compared to the controls (Figure 1C). Moderate absolute agreement between the two raters was observed in their wound healing score ratings (ICC = 0.615). Conclusions: Our results indicate that PPCNg-mediated delivery of Adv-TGF-β1 enhanced the early (3 weeks) healing of the meniscus lesion in rats compared with control (Adv-GFP) gene therapy. Further, localized administration of Adv-TGF-β1 induced greater neovascularization, better organization of collagen fibers, and increased hypercellularity at the injury site in the Adv-TGFβ-1 rat group compared with controls at 3 weeks post-injury. These results together suggest that TGF-β1 gene therapy may enhance meniscus healing by inducing more cellular proliferation and infiltration and greater neovascularization at the injury site to serve as nourishment for the establishment of new wound matrix, leading to more significant deposition and remodeling of mature collagen matrix. Further study that includes larger sample sizes, confirmation of successful gene transfer to meniscal cells around the tear site, and investigations of both later time points of wound healing and the mechanisms by which local TGF-β1 gene therapy may modulate augmented meniscus healing in this rat model of meniscal defect is necessary to better determine the potential future clinical utility of local TGF-β1 gene therapy to treat of meniscus tears with poor healing capacity. [Table: see text]

ACTIfit™: 38% full resorption at 8 years in a cohort of 18 cases

BackgroundPreserving meniscal tissue is a major priority in young, physically active patients. Extensive meniscal defects may result in exercise pain and premature osteoarthritis. ACTIfit™ is a synthetic meniscal substitute that may improve short-term functional scores via biological integration with meniscal tissue regeneration. However, long-term data on the lifespan and chondroprotective effect of this newly formed tissue are lacking. The primary objective of this study was to assess the biological integration of ACTIfit™ based on magnetic resonance imaging (MRI) findings. The secondary objective was to evaluate long-term clinical outcomes. HypothesisThe ACTIfit™ meniscal substitute undergoes biological integration over time, suggesting chondroprotective potential. Materials and methodsA 2014 report by Baynat et al. described the 2-year clinical and radiological outcomes of 18 patients after ACTIfit™ implantation at the Clermont-Tonnerre military teaching hospital (Brest, France). The patients had chronic knee pain of at least 6 months’ duration after failure of primary meniscal surgery with segmental meniscal defects. Mean age was 34.0±7.9 years. A concomitant procedure was performed in 13 (60%) patients, including osteotomy in 8 and ligament reconstruction in 5. For the current study, the clinical and radiological follow-up was at least 8 years. Assessments were with the Genovese grading scale for substitute morphology on MRI scans, International Cartilage Research Society (ICRS) score for osteoarthritis progression, and Lysholm score for clinical outcome. Failure was defined as total substitute resorption (Genovese morphology grade 1) or revision surgery with implant removal, conversion to meniscus allografting, or arthroplasty. ResultsMRI scans were available for 12 (66%) patients. The reason for not having long-term MRI scans was surgery for substitute removal or arthroplasty in 3 of the remaining 6 patients. Complete implant resorption (Genovese grade 1) was noted in 7/12 (58%) patients and osteoarthritis progression to ICRS grade 3 in 4/12 (33%) patients. At last follow-up, the mean Lysholm score was significantly improved vs. baseline (79±15 vs. 55±13, P=0.005). ConclusionThe frequency of complete ACTIfit™ resorption 8 years after implantation was high. This finding argues against ability of this substitute to induce the regeneration of durable meniscal tissue with a chondroprotective effect. The clinical outcome score was significantly improved at last follow-up. However, no conclusions can be drawn regarding the effectiveness of ACTIfit™ given the high frequency of concomitant surgical procedures. Level of evidenceIV, retrospective observational cohort

Repairing Avascular Meniscal Lesions by Recruiting Endogenous Targeted Cells Through Bispecific Synovial-Meniscal Aptamers

Background: Tissue engineering is a promising treatment option for meniscal lesions in the avascular area, but a favorable cell source and its utilization in tissue-engineered menisci remain uncertain. Therefore, a more controllable and convenient method for cell recruitment is required. Hypothesis: Circular bispecific synovial-meniscal (S-M) aptamers with a gelatin methacryloyl (GelMA) hydrogel can recruit endogenous synovial and meniscal cells to the site of the defect, thereby promoting in situ meniscal regeneration and chondroprotection. Study Design: Controlled laboratory study. Methods: Synovial and meniscal aptamers were filtered through systematic evolution of ligands by exponential enrichment (SELEX) and cross-linked to synthesize the S-M aptamer. A GelMA-aptamer system was constructed. An in vitro analysis of the bi-recruitment of synovial and meniscal cells was performed, and the migration and proliferation of the GelMA-aptamer hydrogel were also tested. For the in vivo assay, rabbits (n = 90) with meniscal defects in the avascular zone were divided into 3 groups: repair with the GelMA-aptamer hydrogel (GelMA-aptamer group), repair with the GelMA hydrogel (GelMA group), and no repair (blank group). Regeneration of the repaired meniscus and degeneration of the cartilage were assessed by gross and histological evaluations at 4, 8, and 12 weeks postoperatively. The mechanical properties of repaired menisci were also evaluated. Results: In vitro synovial and meniscal cells were recruited simultaneously by the S-M aptamer with high affiliation and specificity. The GelMA-aptamer hydrogel promoted the migration of targeted cells. Compared with the other groups, the GelMA-aptamer group showed enhanced fibrocartilaginous regeneration, lower cartilage degeneration, and better mechanical strength at 12 weeks after meniscal repair. Conclusion/Clinical Relevance: Bispecific S-M aptamers could be used for avascular meniscal repair by recruiting endogenous synovial and meniscal cells and promoting fibrocartilaginous regeneration.

Segmental meniscal replacement

Meniscal damage results in higher peak stress on the articular cartilage and leads to cartilage degeneration and osteoarthritis. Thus, in recent years there has been an increasing tendency to “save the meniscus” and to repair meniscal defects. However, this is not always possible and restoring meniscal function using scaffolds fulfills this gap. This approach requires the physical presence of an artificial meniscus to allow successful migration and colonization with precursor cells and vessels that lead to the development of organized meniscal tissue. Two meniscal scaffolds are currently available; 1 composed of aliphatic polyurethane named Actifit (Orteq Sports Medicine, Ltd.), and one based on collagen type I fibers called Collagen Meniscus Implant (Stryker Kalamazoo). Both provide an effective and safe solution to treat symptomatic patients with segmental meniscus mid-substance defects. Indeed, recent studies have demonstrated their ability to significantly improve patient satisfaction and clinical evaluation in the mid- to long-term. As such, these approaches hold great promise as a meniscus preservation option to facilitate long-term knee health.

Bone Marrow–Derived Fibrin Clots Stimulate Healing of a Knee Meniscal Defect in a Rabbit Model

To determine the invivo effectiveness of bone marrow aspirate-derived (BMA) fibrin clots for avascular meniscal defect healing in a rabbit model. In 42 Japanese white rabbits, a 2.0-mm cylindrical defect was introduced into the avascular zone of the anterior part of the medial meniscus in the bilateral knees. The rabbits were grouped according to implantation of a BMA fibrin clot (BMA group) or a peripheral blood (PB)-derived clot (PB group) into the defect and nonimplantation (control group). Macroscopic and histological assessments were performed using a scoring system at 4 and 12 weeks after surgery. At 12 weeks after surgery, compressive stress was analyzed biomechanically. The meniscal score in the BMA group (12.1) was greater than that in the PB group (5.5; P= .031) and control group (4.4; P= .013) at 4 weeks. The meniscal score in the BMA group (13.1) was greater than that in the control group (6.4; BMA= 13.1; P= .0046) at 12 weeks. In the biomechanical analysis, the BMA group demonstrated significantly higher compressive strength than the PB group (6.6 MPa) (BMA= 15.4 MPa; P= .0201) and control group (3.6 MPa; BMA= 15.4 MPa; P= .007). Implantation of BMA fibrin clots into the meniscal defect of the avascular zone in a rabbit model improved the meniscal score at 4 weeks and strengthened the reparative meniscal tissue at 12 weeks compared with the implantation of PB fibrin clots. Healing in the avascular zone of the meniscus can be problematic. Approaches to improving this healing response have had variable results. This study provides additional information that may help improve the outcomes in patients with these injuries.

The Potential of Using an Autogenous Tendon Graft by Injecting Bone Marrow Aspirate in a Rabbit Meniscectomy Model.

Bone marrow aspirate (BMA) is an excellent source of cells and growth factors and has been used successfully for bone, cartilage, and soft-tissue healing. This study aimed to investigate the histological and biomechanical properties of autogenous tendon graft by injecting BMA and its protective effect against degenerative changes in a rabbit model of meniscal defects. Adult white rabbits were divided into untreated, tendon, and tendon + BMA groups, and meniscal defects were created in the knees. The tendon graft and articular cartilage status were evaluated by macroscopic and histological analysis at 4, 12, and 24 weeks postoperatively among the three groups. The tendon graft in the tendon and tendon + BMA groups were used for biomechanical evaluation at 4, 12, and 24 weeks postoperatively. The meniscal covering ratio in the tendon + BMA group was better than that in the tendon and untreated groups at 12 and 24 weeks postoperatively. The matrix around the central portion of cells in the tendon + BMA group was positively stained by safranin O and toluidine blue staining with metachromasia at 24 weeks. The histological score of the tendon graft in the tendon + BMA group was significantly higher than that in the untreated and tendon groups at 12 and 24 weeks postoperatively. In the tendon + BMA group, cartilage erosion was not shown at 4 weeks, developed slowly, and was better preserved at 12 and 24 weeks compared to the untreated and tendon groups. Histological scores for the articular cartilage were significantly better in the tendon + BMA group at 24 weeks. The compressive stress on the tendon graft in the tendon + BMA group was significantly higher than that in the tendon group at 12 weeks postoperatively. Transplantation of autogenous tendon grafts by injecting BMA improved the histologic score of the regenerated meniscal tissue and was more effective than the tendon and untreated group for preventing cartilage degeneration in a rabbit model of massive meniscal defects.

Knee meniscus regeneration using autogenous injection of uncultured adipose tissue-derived regenerative cells.

IntroductionThe low healing potential of mature menisci necessitates traditional surgical removal (meniscectomy) to eliminate acute or chronic degenerative tears. However, removal of meniscal tissue is main factor causing osteoarthritis. Adipose tissue-derived regenerative cells (ADRCs), a heterogeneous cell population that includes multipotent adipose-derived stem cells and other progenitor cells, were easily isolated in large amounts from autologous adipose tissue, and same-day processing without culture or expansion was possible. This study investigated the regenerative potential of autologous ADRCs for use in meniscus defects.MethodsIn 10- to 12-week-old male SD rat partial meniscectomy model, an atelocollagen sponge scaffold without or with ADRCs (5.0 × 105 cells) was injected into each meniscus defect. Reconstructed menisci were subjected to histologic, and dynamic mechanical analyses.ResultsAfter 12 weeks, areas of regenerated meniscal tissue in the atelocollagen sponge scaffold in rats with ADRCs (64.54 ± 0.52%, P < 0.05, n = 10) were larger than in those without injection (57.96 ± 0.45%). ADRCs were shown capable of differentiating chondrocyte-like cells and meniscal tissue components such as type II collagen. Higher elastic moduli and lower fluid permeability of regenerated meniscal tissue demonstrated a favorable structure-function relationship required for native menisci, most likely in association with micron-scale porosity, with the lowest level for tissue integrity possibly reproducible.ConclusionsThis is the first report of meniscus regeneration induced by injection of ADRCs. The results indicate that ADRCs will be useful in future clinical cell-based therapy strategies, including as a cell source for reconstruction of damaged knee menisci.

Arthroscopic centralization reduces extrusion of the medial meniscus with posterior root defect in the ACL reconstructed knee.

The purpose of this study was to evaluate the effects of arthroscopic meniscal centralization reinforcement for a medial meniscus (MM) posterior root defect on knee kinematics and meniscal extrusion in the anterior cruciate ligament reconstructed (ACLR) knee. The hypothesis was that the medial meniscus centralization would reduce extrusion and anterior laxity in ACLR knee with a medical meniscal defect. Fourteen fresh-frozen human cadaveric knees were tested using a six-degrees-of-freedom robotic system under the following loading conditions: (a) an 89.0N anterior tibial load, (b) 5.0 Nm internal and external rotational torques, (c) a 10.0Nm valgus and varus loadings, and (d) a combined 7.0Nm valgus moment and then a 5.0Nm internal rotation torque as a static simulated pivot shift. The tested knee states included: (1) anatomic single-bundle cruciate ligament reconstruction with intact medial meniscus (MM Intact), (2) anatomic single-bundle cruciate ligament reconstruction with medial meniscus posterior root defect (MM Defect), (3) Anatomic single-bundle cruciate ligament reconstruction with medial meniscus arthroscopic centralization (MM Centralization). Medial meniscus arthroscopic centralization was performed using 1.4mm anchors with #2 suture. The MM extrusion (MME) was measured using ultrasound under unloaded and varus loading conditions at 0° and 30° of flexion. Anterior tibial translation (ATT) increased significantly with MM posterior root defect compared to MM intact at all flexion angles. With MM centralization, ATT was not significantly different from the intact meniscus at 15° and 30° of flexion. Meniscus extrusion increased significantly with the root defect compared to intact meniscus and decreased significantly with meniscal centralization compared to the root defect at both flexion angles. In ACL reconstruction, cases involving irreparable medial meniscal posterior root tears, applying arthroscopic centralization for avoiding the meniscal extrusion should be considered. Clinically, in ACL reconstruction cases with irreparable medial meniscal posterior root tears, applying arthroscopic meniscal centralization for avoiding the meniscal extrusion should be considered. Meniscal centralization decreases the extrusion of the MM and offers improvements in knee laxity.

Regeneration Using Adipose-Derived Stem Cell Sheets in a Rabbit Meniscal Defect Model Improves Tensile Strength and Load Distribution Function of the Meniscus at 12 Weeks

The purpose of this study was to evaluate the mechanical properties, such as the tensile strength and load distribution function, of the meniscus tissue regenerated using adipose-derived stem cell (ADSC) sheets in a rabbit meniscal defect model. ADSC sheets were prepared from adipose tissue of rabbits. The anterior half of the medial meniscus was removed from both knees. One knee was transplanted with an ADSC sheet; the contralateral knee was closed without transplantation. Mechanical tests were performed at 4 and 12 weeks posttransplantation. In the tensile test, tensile force was applied to the entire medial meniscus, including the normal area (n= 10/group). Compression tests were performed on the entire knee, with soft tissues other than the ligament removed. A pressure-sensitive film was inserted under the medial meniscus and a 40-N load was applied (n= 5/group). In the tensile test, the elastic modulus in ADSC-treated knees was higher at 12 weeks (ADSC: 70.30 ± 18.50 MPa, control: 43.71 ± 7.11 MPa, P= .009). The ultimate tensile strength (UTS) in ADSC-treated knees at 12 weeks was also higher (ADSC: 22.69 ± 5.87 N, control: 15.45 ± 4.08 N, P= .038). In the compression test, the contact area was larger in the ADSC group at 4 weeks (ADSC: 31.60 ± 8.17 mm2, control: 20.33 ± 2.86 mm2, P= .024) and 12 weeks (ADSC: 41.07 ± 6.09 mm2, control: 30.53 ± 5.47 mm2, P= .04). Peak pressure was significantly lower in ADSC-treated knees at 12 weeks (ADSC: 11.91 ± 1.03 MPa, control: 15.53 ± 2.3 MPa, P= .002). The regenerated meniscus tissue, 12 weeks after transplantation of the ADSC sheets into the meniscal defect area, had high elastic modulus and UTS. In the meniscus-tibia compartment, the contact area was large and the peak pressure was low. ADSC sheets promoted regeneration of meniscus. ADSC sheet transplantation for meniscal defects could be an effective regenerative therapy.

Mid-term effectiveness analysis of combined knee extensor mechanism realignment with bone anchor for recurrent patella dislocation

To explore the mid-term effectiveness of combined knee extensor mechanism realignment with bone anchor for recurrent patella dislocation. Between August 2017 and May 2019, 21 patients with recurrent patella dislocation underwent combined knee extensor mechanism realigament with bone anchor and followed up more than 3 years. There were 8 males and 13 females with an average age of 19.4 years (range, 13-26 years). All 21 patients had a history of recurrent patellar dislocation for 2-5 times (median, 3 times), and the disease duration was 1-16 years (mean, 5 years). The preoperative Lysholm score was 67.5±6.3 and the Kujula score was 64.1±7.0. The defect of meniscus, anterior and posterior cruciate ligaments, and medial and lateral collateral ligaments were excluded by MRI examination; CT examination showed that the tibial tuberosity-trochlear groove distance was 2.05-2.56 cm, with an average of 2.16 cm; X-ray examination showed that lower limb force line was abnormal. The effectiveness were evaluated by Lysholm score and Kujula score before operation and at 3 years after operation, and Insall evaluation standard at 3 years after operation. All the incisions healed by first intention, and there was no surgical complication such as lower extremity deep vein thrombosis, incision infection, and nerve injury. All 21 patients were followed up 3.0-3.5 years, with an average of 3.2 years. Anteroposterior and lateral X-ray films of the knee joint at 3 years after operation showed that the position of the patella was normal, and the axial X-ray films of the patella (30°, 60°, 90°) showed that the patellofemoral joint had a good relationship. During the follow-up, there was no anchor drop or fracture, no obvious pseudarthrosis formation, and no epiphyseal injury in the minor patients. The Lysholm score was 91.5±7.1 and the Kujula score was 88.1±7.6 at 3 years after operation, which were significantly improved when compared with those before operation ( t=11.57, P=0.00; t=12.78, P=0.00). According to the Insall evaluation criteria, 12 cases were excellent, 4 cases were good, 4 cases were fair, and 1 case was poor, with an excellent and good rate of 76.2%. Combined knee extensor mechanism realignment with bone anchor is a simple and reliable way to treat the recurrent patella dislocation, with a satisfactory mid-term effectiveness and less complications; however, its long-term effectiveness needs further follow-up.

The Design and Characterization of a Strong Bio-Ink for Meniscus Regeneration.

The meniscus is vital to the mechanical function of the knee, while it is frequently harmed because it bears a heavy load. A strong bio-ink for meniscus regeneration was prepared for the future meniscal tissue engineering. The prepared bio-ink consists of poly (vinyl alcohol) and decellularized extracellular matrix (PVA/dECM). The mechanical properties and the rheological features were explored to evaluate the effects of freezing/thawing cycles and alkaline treatment process. The printability was verified using a three-dimensional printer. The endothelial cells were employed to assess the biocompatibility. Finally, a 12-week rabbit meniscus defect model was established to evaluate the meniscus regeneration capability. We found that the bio-ink by soaking in alkaline for 40 min and 20 freezing/thawing cycles demonstrated excellent mechanical properties. The Young's modulus reached 0.49 MPa and the stress limitation was 2.9 MPa. The results also showed good printability and biocompatibility of the proposed bio-ink in vitro. The PVA/dECM hydrogel healed the meniscus defect after 12 weeks of implantation. The articular cartilage and subchondral bone exhibited normal microstructure and composition. These results suggested that the PVA/dECM hydrogel could be a promising solution to repair meniscal lesions with preventive effects against degenerative meniscal tears and post-traumatic arthritis.