• cell therapy
• meniscal regeneration
• meniscal repair
• meniscus
• meniscus lesions
• stem cells
• tissue engineering
• treatment strategy

• Animals
• Rabbits
• Systematic Reviews as Topic
• Meniscus
• Tissue Engineering/methods
• Models, Animal
• Mesenchymal Stem Cells

Menisci are crucial structures for knee homeostasis. After a meniscal lesion, the golden rule, now, is to save as much meniscus as possible; only the meniscus tissue that is identified as unrepairable should be excised, and meniscal sutures find more and more indications. Several different methods have been proposed to improve meniscal healing. They include very basic techniques, such as needling, abrasion, trephination and gluing, or more complex methods, such as synovial flaps, meniscal wrapping or the application of fibrin clots. Basic research of meniscal substitutes has also become very active in the last decades. The aim of this literature review is to analyze possible therapeutic and surgical options that go beyond traditional meniscal surgery: from scaffolds, which are made of different kind of polymers, such as natural, synthetic or hydrogel components, to new technologies, such as 3-D printing construct or hybrid biomaterials made of scaffolds and specific cells. These recent advances show that there is great interest in the development of new materials for meniscal reconstruction and that, with the development of new biomaterials, there will be the possibility of better management of meniscal injuries

• bioengineering
• biomaterial
• bioprinting
• meniscus
• polymer
• scaffold
• stem cells

The meniscus is a semilunar fibrocartilage structure that plays important roles in maintaining normal knee biomechanics and function. The roles of the meniscus, including load distribution, force transmission, shock absorption, joint stability, lubrication, and proprioception, have been well established. Injury to the meniscus can disrupt overall joint stability and cause various symptoms including pain, swelling, giving-way, and locking. Unless treated properly, it can lead to early degeneration of the knee joint. Because meniscal injuries remain a significant challenge due to its low intrinsic healing potential, most notably in avascular and aneural inner two-thirds of the area, more efficient repair methods are needed. Mesenchymal stem cells (MSCs) have been investigated for their therapeutic potential in vitro and in vivo. Thus far, the application of MSCs, including bone marrow-derived, synovium-derived, and adipose-derived MSCs, has shown promising results in preclinical studies in different animal models. These preclinical studies could be categorized into intra-articular injection and tissue-engineered construct application according to delivery method. Despite promising results in preclinical studies, there is still a lack of clinical evidence. This review describes the basic knowledge, current treatment, and recent studies regarding the application of MSCs in treating meniscal injuries. Future directions for MSC-based approaches to enhance meniscal healing are suggested.

• Meniscus
• Meniscus healing
• Cell-based treatment
• Mesenchymal stem cell
• Tissue engineering

• bioactive scaffolds
• core–shell nanofibers
• electrospun scaffolds
• meniscus
• nanofibers
• tissue engineering

• Mesenchymal stem cell
• Red panda
• cell culture
• multilineage differentiation

• Meniscus
• Regenerative medicine
• Scaffolds
• Stem cell
• Tissue engineering

Meniscal injury is typically treated surgically via partial meniscectomy, which has been shown to cause cartilage degeneration in the long-term. Consequently, research has focused on meniscal prevention and replacement. However, none of the materials or implants developed for meniscal replacement have yet achieved widespread acceptance or demonstrated conclusive chondroprotective efficacy.

A redesigned silk fibroin scaffold, which already displayed promising results regarding biocompatibility and cartilage protection in a previous study, was characterised in terms of its biomechanical, structural and biological functionality to serve as a potential material for permanent partial meniscal replacement. Therefore, different quasi-static but also dynamic compression tests were performed. However, the determined compressive stiffness (0.56 ± 0.31 MPa and 0.30 ± 0.12 MPa in relaxation and creep configuration, respectively) was higher in comparison to the native meniscal tissue, which could potentially disturb permanent integration into the host tissue. Nevertheless, µ-CT analysis met the postulated requirements for partial meniscal replacement materials in terms of the microstructural parameters, like mean pore size (215.6 ± 10.9 µm) and total porosity (80.1 ± 4.3%). Additionally, the biocompatibility was reconfirmed during cell culture experiments. The current study provides comprehensive mechanical and biological data for the characterisation of this potential replacement material. Although some further optimisation of the silk fibroin scaffold may be advantageous, the silk fibroin scaffold showed sufficient biomechanical competence to support loads already in the early postoperative phase.

• Biomechanical tests
• Meniscus replacement
• Silk scaffold
• µ-CT

• biomaterials
• meniscus
• progenitors
• regenerative medicine
• tissue engineering

• Animals
• Bioprosthesis
• Humans
• Meniscus/injuries
• Meniscus/physiology
• Osteoarthritis, Knee/prevention & control
• Regeneration
• Tibial Meniscus Injuries/therapy
• Tissue Engineering/methods

• IK2 RX000760 RRD VA
• U54 GM115677 NIGMS NIH HHS

• Biomaterials
• Knee meniscus; biomaterials
• Materials science
• Scaffolds
• Tissue engineering

Meniscus damage can be caused by trauma or degeneration and is therefore common among patients of all ages. Repair or regeneration of the menisci could be of great importance not only for pain relief or regaining function but also to prevent degenerative disease and osteoarthritis. Current treatment does not offer consistent long-term improvement. Although preclinical research focusing on augmentation of meniscal tear repair and regeneration after meniscectomy is encouraging, clinical translation remains difficult.

To systematically evaluate the literature on in vivo meniscus regeneration and explore the optimal cell sources and conditions for clinical translation. We aimed at thorough evaluation of current evidence as well as clarifying the challenges for future preclinical and clinical studies.

Systematic review.

A search was conducted using the electronic databases of MEDLINE, Embase, and the Cochrane Collaboration. Search terms included meniscus, regeneration, and cell-based.

After screening 81 articles based on title and abstract, 51 articles on in vivo meniscus regeneration could be included; 2 additional articles were identified from the references. Repair and regeneration of the meniscus has been described by intra-articular injection of multipotent mesenchymal stromal (stem) cells from adipose tissue, bone marrow, synovium, or meniscus or the use of these cell types in combination with implantable or injectable scaffolds. The use of fibrochondrocytes, chondrocytes, and transfected myoblasts for meniscus repair and regeneration is limited to the combination with different scaffolds. The comparative in vitro and in vivo studies mentioned in this review indicate that the use of allogeneic cells is as successful as the use of autologous cells. In addition, the implantation or injection of cell-seeded scaffolds increased tissue regeneration and led to better structural organization compared with scaffold implantation or injection of a scaffold alone. None of the studies mentioned in this review compare the effectiveness of different (cell-seeded) scaffolds.

There is heterogeneity in animal models, cell types, and scaffolds used, and limited comparative studies are available. The comparative in vivo research that is currently available is insufficient to draw strong conclusions as to which cell type is the most promising. However, there is a vast amount of in vivo research on the use of different types of multipotent mesenchymal stromal (stem) cells in different experimental settings, and good results are reported in terms of tissue formation. None of these studies compare the effectiveness of different cell-scaffold combinations, making it hard to conclude which scaffold has the greatest potential.

• knee
• meniscus
• regenerative medicine
• stem cell therapy
• tissue scaffolds

• additive manufacturing
• meniscal scaffold
• scaffold design and fabrication

Objective: To induce growth of a neomeniscus into the pores of a prosthesis in order to protect the knee joint cartilage. Methods: 70 knees of 35 New Zealand rabbits were operated. The rabbits were five to seven months old, weighed 2 to 3.8 kilograms, and 22 were male and 13 were female. Each animal underwent medial meniscectomy in both knees during a single operation. A bioabsorbable polymeric meniscal prosthesis composed of 70% polydioxanone and 30% L-lactic acid polymer was implanted in one side. The animals were sacrificed after different postoperative time intervals. The femoral condyles and neomeniscus were subjected to histological analysis. Histograms were used to measure the degradation and absorption of the prosthesis, the growth of meniscal tissue in the prosthesis and the degree of degradation of the femoral condyle joint cartilage. Results: The data obtained showed that tissue growth histologically resembling a normal meniscus occurred, with gradual absorption of the prosthesis, and the percentages of chondrocytes on the control side and prosthesis side. Conclusion: Tissue growth into the prosthesis pores that histologically resembled the normal rabbit meniscus was observed. The joint cartilage of the femoral condyles on the prosthesis side presented greater numbers of chondrocytes in all its layers.

• Cartilage
• Knee
• Prostheses and implants

• Animals
• Biocompatible Materials/chemistry
• Biomechanical Phenomena
• Cell Adhesion
• Cell Proliferation
• Cell Shape
• Cells, Cultured
• Chondrocytes/cytology
• Chondrocytes/physiology
• Chondrocytes/transplantation
• Chondroitin Sulfates/chemistry
• Collagen Type I/chemistry
• Extracellular Matrix/metabolism
• Humans
• Hyaluronic Acid/chemistry
• Knee Injuries/pathology
• Knee Injuries/physiopathology
• Knee Injuries/surgery
• Lactic Acid/chemistry
• Materials Testing
• Menisci, Tibial/pathology
• Menisci, Tibial/physiopathology
• Molecular Conformation
• Polyglycolic Acid/chemistry
• Polylactic Acid-Polyglycolic Acid Copolymer
• Tibial Meniscus Injuries
• Tissue Engineering/methods
• Tissue Scaffolds/chemistry
• Wound Healing/physiology

This study was undertaken to examine whether bone morphogenetic protein 7 (BMP-7) induces ectopic cartilage formation in the rat tendon, and whether transplantation of tendon treated with BMP-7 promotes meniscal regeneration. Additionally, we analyzed the relative contributions of host and donor cells on the healing process after tendon transplantation in a rat model.

BMP-7 was injected in situ into the Achilles tendon of rats, and the histologic findings and gene profile were evaluated. Achilles tendon injected with 1 μg of BMP-7 was transplanted into a meniscal defect in rats. The regenerated meniscus and articular cartilage were evaluated at 4, 8, and 12 weeks. Achilles tendon from LacZ-transgenic rats was transplanted into the meniscal defect in wild-type rats, and vice versa.

Injection of BMP-7 into the rat Achilles tendon induced the fibrochondrocyte differentiation of tendon cells and changed the collagen gene profile of tendon tissue to more closely approximate meniscal tissue. Transplantation of the rat Achilles tendon into a meniscal defect increased meniscal size. The rats that received the tendon treated with BMP-7 had a meniscus matrix that exhibited increased Safranin O and type II collagen staining, and showed a delay in articular cartilage degradation. Using LacZ-transgenic rats, we determined that the regeneration of the meniscus resulted from contribution from both donor and host cells.

Our findings indicate that BMP-7 induces ectopic cartilage formation in rat tendons. Transplantation of Achilles tendon treated with BMP-7 promotes meniscus regeneration and prevents cartilage degeneration in a rat model of massive meniscal defect. Native cells in the rat Achilles tendon contribute to meniscal regeneration.

Adipose tissue-derived stem cells (ADSCs), a type of mesenchymal stem cells (MSCs), have great potential as therapeutic agents in regenerative medicine. Numerous animal studies have documented the multipotency of ADSCs, showing their capabilities to differentiate into tissues such as muscle, bone, cartilage, and tendon. However, the safety of autologous ADSC injections into human joints is only beginning to be understood and the data are lacking.

Between 2009 and 2010, 91 patients were treated with autologous ADSCs with platelet-rich plasma (PRP) for various orthopedic conditions. Stem cells in the form of stromal vascular fraction (SVF) were injected with PRP into various joints (n = 100). All patients were followed for symptom improvement with visual analog score (VAS) at one month and three months. Approximately one third of the patients were followed up with third month magnetic resonance imaging (MRI) of the injected sites. All patients were followed up by telephone questionnaires every six months for up to 30 months.

The mean follow-up time for all patients was 26.62 ± 0.32 months. The follow-up time for patients who were treated in 2009 and early 2010 was close to three years. The relative mean VAS of patients at the end of one month follow-up was 6.55 ± 0.32, and at the end of three months follow-up was 4.43 ± 0.41. Post-procedure MRIs performed on one third of the patients at three months failed to demonstrate any tumor formation at the implant sites. Further, no tumor formation was reported in telephone long-term follow-ups. However, swelling of injected joints was common and was thought to be associated with death of stem cells. Also, tenosinovitis and tendonitis in elderly patients, all of which were either self-limited or were remedied with simple therapeutic measures, were common as well.

Using both MRI tracking and telephone follow ups in 100 joints in 91 patients treated, no neoplastic complications were detected at any ADSC implantation sites. Based on our longitudinal cohort, the autologous and uncultured ADSCs/PRP therapy in the form of SVF could be considered to be safe when used as percutaneous local injections.

• Alginates/chemistry
• Animals
• Bioartificial Organs
• Cattle
• Cells, Cultured
• Collagen Type I/chemistry
• Collagen Type I/ultrastructure
• Equipment Design
• Equipment Failure Analysis
• Gels/chemistry
• Glucuronic Acid/chemistry
• Hexuronic Acids/chemistry
• Materials Testing
• Menisci, Tibial/cytology
• Menisci, Tibial/growth & development
• Surface Properties
• Tissue Engineering/instrumentation
• Tissue Scaffolds

• cartilage
• collagen
• glycosaminoglycans
• medial collateral ligament, knee

Mesenchymal stem cells from several sources (bone marrow, synovial tissue, cord blood, and adipose tissue) can differentiate into variable parts (bones, cartilage, muscle, and adipose tissue), representing a promising new therapy in regenerative medicine. In animal models, mesenchymal stem cells have been used successfully to regenerate cartilage and bones. However, there have been no follow-up studies on humans treated with adipose-tissue-derived stem cells (ADSCs) for the chondromalacia patellae. To obtain ADSCs, lipoaspirates were obtained from lower abdominal subcutaneous adipose tissue. The stromal vascular fraction was separated from the lipoaspirates by centrifugation after treatment with collagenase. The stem-cell-containing stromal vascular fraction was mixed with calcium chloride-activated platelet rich plasma and hyaluronic acid, and this ADSCs mixture was then injected under ultrasonic guidance into the retro-patellar joints of all three patients. Patients were subjected to pre- and post-treatment magnetic resonance imaging (MRI) scans. Pre- and post-treatment subjective pain scores and physical therapy assessments measured clinical changes. One month after the injection of autologous ADSCs, each patient's pain improved 50–70%. Three months after the treatment, the patients' pain improved 80–90%. The pain improvement persisted over 1 year, confirmed by telephone follow ups. Also, all three patients did not report any serious side effects. The repeated magnetic resonance imaging scans at three months showed improvement of the damaged tissues (softened cartilages) on the patellae-femoral joints. In patients with chondromalacia patellae who have continuous anterior knee pain, percutaneous injection of autologous ADSCs may play an important role in the restoration of the damaged tissues (softened cartilages). Thus, ADSCs treatment presents a glimpse of a new promising, effective, safe, and non-surgical method of treatment for chondromalacia patellae.

• Acute Pain/therapy
• Adult
• Chondromalacia Patellae/therapy
• Female
• Humans
• Male
• Middle Aged
• Musculoskeletal Pain/therapy
• Pain Measurement
• Regenerative Medicine
• Retrospective Studies
• Stem Cell Transplantation
• Subcutaneous Fat, Abdominal/pathology
• Transplantation, Autologous
• Treatment Outcome

• Collagen
• Hydrogels
• Microscopy, Electron, Scanning
• Molecular Structure
• Nanostructures
• Rosaniline Dyes
• Tissue Engineering

• G0700869 Medical Research Council

• Absorbable Implants
• Animals
• Biomechanical Phenomena
• Dogs
• Menisci, Tibial/surgery
• Suture Techniques
• Tensile Strength
• Tibial Meniscus Injuries
• Wound Healing/physiology

• Animals
• Cattle
• Cells, Cultured
• DNA, Complementary
• Gene Transfer Techniques
• Genes, Reporter
• Genetic Engineering
• Humans
• Menisci, Tibial/cytology
• Mesenchymal Stem Cells
• Recombinant Proteins/genetics
• Tissue Engineering
• Transforming Growth Factor beta1/genetics