Regeneration Of Meniscal Tissue Research Articles

Photocrosslinkable silk-based bioinks embedded with growth factor loaded microspheres towards cell-free 3D printing approach for biomimetic regeneration of meniscal tissue

Fibrocartilaginous meniscal tear regeneration is a major challenge due to the large avascular regions which suffer several injuries among all age-groups. Mostly, meniscus implants are focused on the development of multi-layered meniscus constructs and scaffolds that mimic the macro-architecture, functionality and mechanical strength. The native human menisci consist of vascular and avascular regions that contain different cellular phenotypes and are hence composed of a gradient of extracellular matrix (ECM) components. The biochemical composition of the inner, middle and outer regions of the knee menisci plays a significant role in the mechanical behavior and its overall functionality. We have developed a photo-polymerizing mulberry and non-mulberry silk-based biomaterial ink which is laden with growth factor loaded gelMA microspheres for the zone-specific regeneration of full thickness meniscus tears using three-dimensional (3D) fabrication. We have fabricated growth factor loaded gelMA microspheres and encapsulated them within the biomaterial ink for controlled release of Connective Tissue Growth Factor (CTGF) and Transforming Growth Factor-beta3 (TGF-β3) from the different zones of the meniscus constructs. The growth factor releasing constructs demonstrate the requisite mechanical resilience, degradability and release behaviour for regeneration of meniscal tissue. The developed growth factor loaded constructs demonstrate zone specific phenotypic differentiation of adipose derived stem cells and extracellular matrix deposition by the differentiated stem cells in vitro. The microsphere loaded constructs were found to be immuno-compatible as well. Therefore, these bioactive microsphere-laden 3D printed meniscus constructs would potentially promote regeneration and integration of meniscal tissue in vivo.

Stem Cell Administration to Repair Torn Menisci

The meniscus is a crescent-shaped, fibrocartilaginous padding in the knee that contains variable vascularization and histology. This structure enables proper loadbearing, knee movement, and protection of articular cartilage and bone of the tibiofemoral joint. The meniscus is subject to tears from acute injury and degenerative stresses. Many meniscal tears do not heal naturally due to poor vascularization and high stresses placed on the meniscus. These often result in pain and mechanical symptoms and are highly correlated to osteoarthritis (OA) development. While there are a wide variety of suggested treatments for meniscal tears, studies indicate common surgical interventions have little to no significant improvements in abating patient symptoms or limiting osteoarthritic progression, with high failure rates. Therefore, alternative treatments are being actively explored for meniscal tear repair. One of the most-researched treatment options is using mesenchymal stem cells (MSC), a type of adult multilineage progenitor cell capable of facilitating meniscal tissue regeneration. Many different types of MSCs and supplemental, cuttingedge techniques are being tested to maximize tear healing. MSCs hold great promise for regenerating meniscal tissue, limiting OA, and restoring joint functionality. However, more research is required to prove the significance of stem cell treatments in humans and define the conditions for their use.

Preclinical Studies and Clinical Trials on Cell-Based Treatments for Meniscus Regeneration.

This study aims at performing a thorough review of cell-based treatment strategies for meniscus regeneration in preclinical and clinical studies. The PubMed, Embase, and Web of Science databases were searched for relevant studies (both preclinical and clinical) published from the time of database construction to December 2022. Data related to cell-based therapies for in situ regeneration of the meniscus were extracted independently by two researchers. Assessment of risk of bias was performed according to the Cochrane Handbook for Systematic Reviews of Interventions. Statistical analyses based on the classification of different treatment strategies were performed. A total of 5730 articles were retrieved, of which 72 preclinical studies and 6 clinical studies were included in this review. Mesenchymal stem cells (MSCs), especially bone marrow MSCs (BMSCs), were the most commonly used cell type. Among preclinical studies, rabbit was the most commonly used animal species, partial meniscectomy was the most commonly adopted injury pattern, and 12 weeks was the most frequently chosen final time point for assessing repair outcomes. A range of natural and synthetic materials were used to aid cell delivery as scaffolds, hydrogels, or other morphologies. In clinical trials, there was large variation in the dose of cells, ranging from 16 × 106 to 150 × 106 cells with an average of 41.52 × 106 cells. The selection of treatment strategy for meniscus repair should be based on the nature of the injury. Cell-based therapies incorporating various "combination" strategies such as co-culture, composite materials, and extra stimulation may offer greater promise than single strategies for effective meniscal tissue regeneration, restoring natural meniscal anisotropy, and eventually achieving clinical translation. Impact Statement This review provides an up-to-date and comprehensive overview of preclinical and clinical studies that tested cell-based treatments for meniscus regeneration. It presents novel perspectives on studies published in the past 30 years, giving consideration to the cell sources and dose selection, delivery methods, extra stimulation, animal models and injury patterns, timing of outcome assessment, and histological and biomechanical outcomes, as well as a summary of findings for individual studies. These unique insights will help to shape future research on the repair of meniscus lesions and inform the clinical translation of new cell-based tissue engineering strategies.

3D printing of mechanically functional meniscal tissue equivalents using high concentration extracellular matrix inks

Decellularized extracellular matrix (dECM) has emerged as a promising biomaterial in the fields of tissue engineering and regenerative medicine due to its ability to provide specific biochemical and biophysical cues supportive of the regeneration of diverse tissue types. Such biomaterials have also been used to produce tissue-specific inks and bioinks for 3D printing applications. However, a major limitation associated with the use of such dECM materials is their poor mechanical properties, which limits their use in load-bearing applications such as meniscus regeneration. In this study, native porcine menisci were solubilized and decellularized using different methods to produce highly concentrated dECM inks of differing biochemical content and printability. All dECM inks displayed shear thinning and thixotropic properties, with increased viscosity and improved printability observed at higher pH levels, enabling the 3D printing of anatomically defined meniscal implants. With additional crosslinking of the dECM inks following thermal gelation at pH 11, it was possible to fabricate highly elastic meniscal tissue equivalents with compressive mechanical properties similar to the native tissue. These improved mechanical properties at higher pH correlated with the development of a denser network of smaller diameter collagen fibers. These constructs also displayed repeatable loading and unloading curves when subjected to long-term cyclic compression tests. Moreover, the printing of dECM inks at the appropriate pH promoted a preferential alignment of the collagen fibers. Altogether, these findings demonstrate the potential of 3D printing of highly concentrated meniscus dECM inks to produce mechanically functional and biocompatible implants for meniscal tissue regeneration. This approach could be applied to a wide variety of different biological tissues, enabling the 3D printing of tissue mimics with diverse applications from tissue engineering to surgical planning.

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

Meniscal Regenerative Scaffolds Based on Biopolymers and Polymers: Recent Status and Applications

Knee menisci are structurally complex components that preserve appropriate biomechanics of the knee. Meniscal tissue is susceptible to injury and cannot heal spontaneously from most pathologies, especially considering the limited regenerative capacity of the inner avascular region. Conventional clinical treatments span from conservative therapy to meniscus implantation, all with limitations. There have been advances in meniscal tissue engineering and regenerative medicine in terms of potential combinations of polymeric biomaterials, endogenous cells and stimuli, resulting in innovative strategies. Recently, polymeric scaffolds have provided researchers with a powerful instrument to rationally support the requirements for meniscal tissue regeneration, ranging from an ideal architecture to biocompatibility and bioactivity. However, multiple challenges involving the anisotropic structure, sophisticated regenerative process, and challenging healing environment of the meniscus still create barriers to clinical application. Advances in scaffold manufacturing technology, temporal regulation of molecular signaling and investigation of host immunoresponses to scaffolds in tissue engineering provide alternative strategies, and studies have shed light on this field. Accordingly, this review aims to summarize the current polymers used to fabricate meniscal scaffolds and their applications in vivo and in vitro to evaluate their potential utility in meniscal tissue engineering. Recent progress on combinations of two or more types of polymers is described, with a focus on advanced strategies associated with technologies and immune compatibility and tunability. Finally, we discuss the current challenges and future prospects for regenerating injured meniscal tissues.

Bioactive proteins delivery through core-shell nanofibers for meniscal tissue regeneration

Mimicking the ultrastructural morphology of the meniscus with nanofiber scaffolds, coupled with controlled growth-factor delivery to the appropriate cells, can help engineer tissue with the potential to grow, mature, and regenerate after in vivo implantation. We electrospun nanofibers encapsulating platelet-derived growth factor (PDGF-BB), which is a potent mitogen and chemoattractant in a core of serum albumin contained within a shell of polylactic acid. We controlled the local PDGF-BB release by adding water-soluble polyethylene glycol to the polylactic acid shell to serve as a porogen. The novel core-shell nanofibers generated 3D scaffolds with an interconnected macroporous structure, with appropriate mechanical properties and with high cell compatibility. Incorporating PDGF-BB increased cell viability, proliferation, and infiltration, and upregulated key genes involved in meniscal extracellular matrix synthesis in human meniscal and synovial cells. Our results support proof of concept that these core-shell nanofibers can create a cell-favorable nanoenvironment and can serve as a system for sustained release of bioactive factors.

Polyurethane meniscal scaffolds lead to better clinical outcomes but worse articular cartilage status and greater absolute meniscal extrusion.

Implantation of polyurethane (PU) meniscal scaffolds has become a popular procedure to provide a scaffold for vessel ingrowth and meniscal tissue regeneration in patients with partial meniscal defects. However, it is unclear whether PU meniscal scaffolds lead to better clinical and magnetic resonance imaging (MRI) outcomes post-operatively. This meta-analysis compared the clinical and MRI outcomes in patients with partial meniscal defects treated with PU meniscal scaffolds. This meta-analysis reviewed all studies that assessed Lysholm score, International Knee Documentation Committee (IKDC) score, visual analogue scale (VAS) for pain, Tegner score, Knee Injury and Osteoarthritis Outcomes Score (KOOS), articular cartilage (AC), absolute meniscal extrusion (AME), morphology and size (MS), signal intensity (SI) of meniscal implant, and interface of the implant-residual meniscus complex (IIRMC) in patients with partial meniscal defects treated with PU meniscal scaffolds. Eighteen studies were included in the meta-analysis. The proportion of patients who evaluated MS (OR 0.71, 95% CI 0.38-1.33; n.s.), SI (OR 1.07, 95% CI 0.53-2.18; n.s.), and IIRMC (OR 1.00, 95% CI 0.33-3.06; n.s.) did not differ significantly between baseline and final follow-up. However, AC (OR 0.31, 95% CI 0.11-0.84; P=0.02) and AME (OR 0.05, 95% CI 0.01-0.18; P<0.00001) worsened between baseline and final follow-up. Conversely, Lysholm score (95% CI -1.87 to -1.07; P<0.00001), IKDC score (95% CI -2.19 to -1.08; P<0.00001), VAS for pain (95% CI -2.29 to -1.07; P<0.00001), Tegner score (95% CI -0.76 to -0.15; P=0.003), and overall KOOS (95% CI -29.48 to -23.17; P<0.00001) were significantly greater at final follow-up when compared to baseline. This meta-analysis found no significant differences in the tested MRI parameters, including MS, SI, and IIRMC. However, AC and AME worsened between baseline and final follow-up. Conversely, patients treated with PU meniscal scaffolds showed significant functional improvement and pain relief when compared with baseline scores. Thus, PU meniscal scaffolds appear to be a viable alternative for patients with partial meniscal defects, although further studies are needed to determine whether worsened AC and AME are clinically relevant. In particular, precise measurement of PU meniscal scaffolds in combination with thorough investigation of the baseline articular cartilage status and meniscal defect size may be effective for pain relief or functional improvement in patients with PU meniscal scaffold implantation. III.

3D-Printed Poly(ε-caprolactone) Scaffold Augmented With Mesenchymal Stem Cells for Total Meniscal Substitution: A 12- and 24-Week Animal Study in a Rabbit Model

Background: Total meniscectomy leads to knee osteoarthritis in the long term. The poly(ε-caprolactone) (PCL) scaffold is a promising material for meniscal tissue regeneration, but cell-free scaffolds result in relatively poor tissue regeneration and lead to joint degeneration. Hypothesis: A novel, 3-dimensional (3D)–printed PCL scaffold augmented with mesenchymal stem cells (MSCs) would offer benefits in meniscal regeneration and cartilage protection. Study Design: Controlled laboratory study. Methods: PCL meniscal scaffolds were 3D printed and seeded with bone marrow–derived MSCs. Seventy-two New Zealand White rabbits were included and were divided into 4 groups: cell-seeded scaffold, cell-free scaffold, sham operation, and total meniscectomy alone. The regeneration of the implanted tissue and the degeneration of articular cartilage were assessed by gross and microscopic (histological and scanning electron microscope) analysis at 12 and 24 weeks postoperatively. The mechanical properties of implants were also evaluated (tensile and compressive testing). Results: Compared with the cell-free group, the cell-seeded scaffold showed notably better gross appearance, with a shiny white color and a smooth surface. Fibrochondrocytes with extracellular collagen type I, II, and III and proteoglycans were found in both seeded and cell-free scaffold implants at 12 and 24 weeks, while the results were significantly better for the cell-seeded group at week 24. Furthermore, the cell-seeded group presented notably lower cartilage degeneration in both femur and tibia compared with the cell-free or meniscectomy group. Both the tensile and compressive properties of the implants in the cell-seeded group were significantly increased compared with those of the cell-free group. Conclusion: Seeding MSCs in the PCL scaffold increased its fibrocartilaginous tissue regeneration and mechanical strength, providing a functional replacement to protect articular cartilage from damage after total meniscectomy. Clinical Relevance: The study suggests the potential of the novel 3D PCL scaffold augmented with MSCs as an alternative meniscal substitution, although this approach requires further improvement before being used in clinical practice.

Intra-articular Implantation of Mesenchymal Stem Cells, Part 2: A Review of the Literature for Meniscal Regeneration.

Knee osteoarthritis (OA) after partial or total meniscectomy is a prevalent issue that patients must face. Various methods of replacing meniscal tissue have been studied to avoid this progression, including meniscal allograft transplantation, meniscal scaffolds, and synthetic meniscus replacement. Studies have shown that meniscal scaffolds may improve symptoms but have not been shown to prevent progression of OA. Recently, mesenchymal stem cells (MSCs) have been proposed as a possible biological therapy for meniscal regeneration. Several animal studies and 1 human study have evaluated the effect of transplanting MSCs into the knee joint after partial meniscectomy. The purpose of this review was to assess the outcomes of intra-articular transplantation of MSCs on meniscal regeneration in animals and humans after partial meniscectomy. Limited results from animal studies suggest that there is some potential for intra-articular injection of MSCs for the regeneration of meniscal tissue. However, further studies are necessary to determine the quality of regenerated meniscal tissue through histological and biomechanical testing.

Postmeniscectomy Meniscus Growth With Stem Cells: Where Are We Now?

Arthroscopic meniscal repair and debridement are some of the most common procedures performed in the field of orthopedic surgery. Further, recent research has suggested poor long-term outcomes for patients with meniscectomies with increased incidence of osteoarthritis, leaving a need to develop technology to regenerate meniscal tissue following meniscectomy. Mesenchymal stem cells, are cells that can be harvested from multiple organs and retain the ability to differentiate into a variety of tissues, including osteoblasts, adipocytes, and chondroblasts. They have been shown to stimulate the regeneration of meniscal tissue in several animal models and recently in humans, as well. This study reviews the current research and clinical data regarding mesenchymal stem cells, specifically with regard to postmeniscectomy meniscus growth with stem cells.

The Knee Joint Tissues Differ Significantly in TGFβ1 Expression and Its Sensitivity

The knee joint is the largest and most complex joint in the human body. In this study, we investigated TGFβ1 expression in the outer meniscus, inner meniscus and articular cartilage of rabbit and human knee tissue (outer and inner menisci) in order to determine the potential role of this factor in normal meniscal function. We also examined the potential of TGF-β1 stimulation to promote tissue regeneration in the two different regions of rabbit knee meniscus tissue. Immunohistochemical investigations of TGF-β1 were performed on rabbit and human knee tissue. The rabbit outer, inner and articular cartilage cells were culture and stimulated with TGF-β1 followed by cell proliferation assay and extracellular matrix analysis. Regulatory studies were performed using TGF-β1 inhibitors SB-431542 and PD98059. Gene expression was analyzed by quantitative polymerase chain reaction. We found marked regional variation in the expression of TGF-β1 in rabbit and human knee. TGF-β1 expressions are relatively greater in the outer meniscus than inner meniscus. Furthermore, we found that exogenous TGF-β1 stimulation increased cell proliferation and aggrecan synthesis more so in the outer than in the inner meniscus. Articular cartilage tissue shows moderate levels of cell proliferation and ECM synthesis when compared with outer and inner meniscus. These findings suggest that growth factors used to enhance the repair and regeneration of meniscal tissue should be tailored to enhance region-specific variation in cell proliferation and extracellular matrix synthesis.

A Novel Patient-Specific Regenerative Meniscal Replacement System

Knee meniscal injuries account for the greatest number of surgical procedures performed by orthopaedic surgeons worldwide. Each year in excess of 400,000 operations are performed in Europe and over one million in the United States and yet no suitable replacement for the meniscus is available. Fibrocartilage tissue engineering holds great potential in the regeneration of meniscal tissue however current developments have been limited. Difficulties in imitating the anisotropic nature of the meniscus, patient specific geometry, attaining sterility assurance requirements remain as developmental challenges for meniscal scaffold devices. A novel approach was developed to rapidly form terminally sterilized pre-packaged scaffold templates into anatomically matched regenerative meniscal implants. Formed meniscal implants exhibited the structural and functional architecture of the native meniscus. Meniscal implants fabricated using this method displayed mechanical properties approaching to that of the native meniscus and imparted rotational stability. Fixation techniques influenced the biomechanical response of implants and 45S5 bioactive glass modification was found to enhance radio-opacity of the scaffold. Biocompatibility of the implant was confirmed using a fibroblast cell culture model.

The safety and short-term efficacy of a novel polyurethane meniscal scaffold for the treatment of segmental medial meniscus deficiency

Meniscal loss is associated with an increased risk of developing osteoarthritis. Tissue engineering solutions, which include the development of novel material scaffolds, are being utilised to aid the regeneration of meniscal tissue. The purpose of this study was to monitor the safety profile and the short-term efficacy of a novel polyurethane meniscal scaffold in the treatment of patients with painful knees following partial medial meniscectomy. Ten consecutive patients with segmental tissue loss from the medial meniscus were treated with the arthroscopic implantation of an Actifit(®) (Orteq Sports Medicine) polyurethane meniscal scaffold. Patients were followed up at 2 and 6 weeks, then again at 6 and 12 months. Primary outcome measures included reporting of complications and patient-reported outcome scores (KOOS, KSS, UCLA Activity scale, VAS pain). Secondary outcome was MRI assessment at 6 and 12 months looking at scaffold morphology, integration and associated joint injury/inflammation. Eight male and 2 female patients were included in the study with a mean age of 29 (range 18-45). No complications were reported. All patients were happy with their surgery. At 6 months, a statistically significant improvement (P < 0.05) in all PROMS except the UCLA activity scale and VAS pain scale were noted. The improvement remained at 12 months. MRI analysis revealed the presence of scaffolds at 6 months, with evidence of some tissue integration in many improvements in scaffold morphology and ICRS classification of cartilage in the medial compartment were noted at 12 months. No synovitis was noted in the joint or adverse reactions in the other compartments. The new Actifit(®) polyurethane scaffold has been shown to be a safe, effective implant, for the treatment of patients with pain as a result of segmental medial meniscus loss at 1 year. IV.

Meniskusimplantate

A partial or total loss of the meniscus leads to development of arthritis as already described in previous studies. Therefore a form of therapy which adequately reconstructs or substitutes the meniscus is important for the treatment of meniscal tears. Attempts at replacing the meniscus by means of autografts or artificial Dacron or Teflon implants achieved insufficient results. Another approach was to develop a scaffold of bovine collagen or polyurethane. According to the results of several studies implantation of a collagen meniscus led to good results overall, however a remodeling into real meniscal tissue could not be demonstrated.Implants of polyurethane result in partly unsatisfactory outcomes in animal experiments, but short-term results of implantations in human knees have so far shown a functional improvement. Collagen meniscus implants are as yet the only valid long-term method besides meniscal allografts to sufficiently substitute meniscal defects. Latest efforts are aimed at conditioning meniscal scaffolds with suitable cells or growth factors to obtain a better regeneration of meniscal tissue.

Implantation of Autogenous Meniscal Fragments Wrapped with a Fascia Sheath Enhances Fibrocartilage Regeneration in Vivo in a Large Harvest Site Defect

Background Concerning meniscal tissue regeneration, many investigators have studied the development of a tissue-engineered meniscus. However, the utility still remains unknown. Hypothesis Implantation of autogenous meniscal fragments wrapped with a fascia sheath into the donor site meniscal defect may significantly enhance fibrocartilage regeneration in vivo in the defect. Study Design Controlled laboratory study. Methods Seventy-five mature rabbits were used in this study. In each animal, an anterior one-third of the right medial meniscus was resected. Then, the animals were divided into the following 3 groups of 25 rabbits each: In group 1, no treatment was applied to the meniscal defect. In group 2, the defect was covered with a fascia sheath. In group 3, after the resected meniscus was fragmented into small pieces, the fragments were grafted into the defect. Then, the defect with the meniscal fragments was covered with a fascia sheath. In each group, 5 rabbits were used for histological evaluation at 3, 6, and 12 weeks after surgery, and 5 rabbits were used for biomechanical evaluation at 6 and 12 weeks after surgery. Results Histologically, large round cells in group 3 were scattered in the core portion of the meniscus-shaped tissue, and the matrix around these cells was positively stained by safranin O and toluisin blue at 12 weeks. The histological score of group 3 was significantly higher than that of group 1 and group 2. Biomechanically, the maximal load and stiffness of group 3 were significantly greater than those of groups 1 and 2. Conclusion This study clearly demonstrated that implantation of autogenous meniscal fragments wrapped with a fascia sheath into the donor site meniscal defect significantly enhanced fibrocartilage regeneration in vivo in the defect at 12 weeks after implantation in the rabbit. Clinical relevance This study proposed a novel strategy to treat a large defect after a meniscectomy.

Platelet derived growth factor-AB enhances knee meniscal cell activity in vitro

Meniscal healing especially in the inner avascular region has always been a major challenge. In this study we investigated the potential for platelet derived growth factor-AB (PDGF-AB) to promote meniscal tissue regeneration in the inner (avascular), middle, and outer (vascular) zones of the meniscus. Various concentrations of PDGF-AB were tested on sheep meniscal cell cultures. We used the radioactive thymidine uptake assay to assess cell proliferation, and the radioactive sulphur and proline uptake assays and Blyscan assay to assess matrix formation. In general, PDGF-AB stimulated both cell proliferation and matrix formation by cells from all meniscal zones. PDGF-AB at a concentration of 100 ng/ml increased cell proliferation and matrix formation by eight and four fold respectively, by fibrochondrocytes cultured from all meniscal zones ( p < 0.001). These results indicate that fibrochondrocytes present within the avascular region of the meniscus have the ability to proliferate and form new matrix when exposed to anabolic cytokines such as PDGF-AB.

The Regenerative Effects of Platelet-Rich Plasma on Meniscal CellsIn Vitroand ItsIn VivoApplication with Biodegradable Gelatin Hydrogel

The objective of the study was to test the hypothesis that platelet-rich plasma (PRP) enhances meniscal tissue regeneration in vitro and in vivo. In the in vitro study, monolayer meniscal cell cultures were prepared, and 3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt assay and 5-bromo-2'-deoxyuridine assay were performed to assess proliferative behavior in the presence of PRP. Alcian blue assay was performed to assess extracellular matrix (ECM) synthesis. To detect the fibrocartilage-related messenger ribonucleic acid (mRNA) expressions, real-time polymerase chain reaction was performed. In the in vivo study, 1.5-mm-diameter full-thickness defects were created in the avascular region of rabbit meniscus. Gelatin hydrogel (GH) was used as the drug delivery system for PRP growth factors. The defects were filled as follows: Group A, GH with PRP; Group B, GH with platelet-poor plasma; Group C, GH only. Each group was evaluated histologically at 4, 8, and 12 weeks after surgery. PRP stimulated deoxyribonucleic acid synthesis and ECM synthesis (p<0.05). Meniscal cells cultured with PRP showed greater mRNA expression of biglycan and decorin (p<0.05). Histological findings showed that remnants of gelatin hydrogels existed at 4 weeks, indicating that the hydrogels could control release for approximately 4 weeks. Histological scoring of the defect sites at 12 weeks revealed significantly better meniscal repair in animals that received PRP with GH than in the other two groups. These findings suggest that PRP enhances the healing of meniscal defects.

The Current Status of Treatment for Large Meniscal Defects

Meniscal pathology causing loss of function is a common problem that requires treatment in a large number of individuals each year. A patient with a meniscal-deficient knee is doomed to the development of osteoarthritis, pain, and knee dysfunction. The amount, shape, and composition of meniscal tissue influence its function and, therefore, influence the health of the knee joint. When preservation of healthy meniscal tissue cannot be accomplished, methods for replacement or regeneration of meniscal tissue are necessary. This review article will discuss current methods of meniscal tissue replacement and regeneration and potential future modes of therapy.

Regional regenerative potential of meniscal cartilage exposed to recombinant insulin-like growth factor-I in vitro.

It is well recognised that meniscal tears situated within the inner, avascular region do not heal. We investigated the potential effect of insulin-like growth factor-I (IGF-I) in promoting regeneration of meniscal tissue in the inner, middle and outer zones of the meniscus. Sheep menisci were harvested and monolayer cell cultures prepared. Various concentrations of IGF-I were used in the presence or absence of 10% fetal calf serum (FCS). We measured the uptake of radioactive thymidine, sulphur, and proline to assess cell proliferation and formation of extracellular matrix (ECM). IGF-I, in the presence or absence of FCS, increased the formation of DNA and ECM in all meniscal zones. However, the response of the cells from the avascular zone was greater than that from the vascular zone. Our findings indicate that fibrochondrocytes cultured from avascular meniscal tissue have the ability to regenerate when exposed to anabolic cytokines such as IGF-I.