Meniscal Replacement Research Articles

Plasticity of Human Meniscus Fibrochondrocytes: A Study on Effects of Mitotic Divisions and Oxygen Tension

Meniscus fibrochondrocytes (MFCs) may be the optimal cell source to repair non-healing meniscus injuries using tissue engineering strategies. In this study, we investigated the effects of mitotic divisions and oxygen tension on the plasticity of adult human MFCs. Our assessment techniques included gene expression, biochemical, histological, and immunofluorescence assays. MFCs were expanded in monolayer culture with combined growth factors TGFβ1 and FGF-2 (T1F2) under normoxia (21% O2). Trilineage (adipogenesis, chondrogenesis and osteogenesis) differentiation was performed under both normoxic (21% O2) and hypoxic (3% O2) conditions. The data demonstrated that MFCs with a mean total population doubling of 10 can undergo adipogenesis and chondrogenesis. This capability was enhanced under hypoxic conditions. The MFCs did not undergo osteogenesis. In conclusion, our findings suggest that extensively expanded human MFCs have the capacity to generate tissues with the functional matrix characteristics of avascular meniscus. To this end, expanded MFCs may be an ideal cell source for engineering functional constructs for the replacement or repair of avascular meniscus.

Development of Novel Orthopaedic Materials

New materials have played a critical role in Orthopaedic for many decades. Early total joints and trauma devices were made from stainless steel then titanium and cobalt-chrome replaced stainless steel in most modern implants. In addition to high-strength structural metals, polymers such as polyethylene were used for many decades in total joints followed by polyether-ether-ketone (PEEK) in spine fusion and then in sports medicine anchors. Biodegradable polymers have also made a strong impact with their beginnings in degradable sutures and current widespread use as an anchoring material in sports medicine reconstructions. This issue covers recent material developments in multiple areas of Orthopaedic surgery, such as soft-tissue fixation, hip arthroplasty, spine fusion, and wound healing. As the title suggests, orthopaedic materials may come from two avenues, emerging into the field or evolving within the field of orthopaedic surgery. Emerging materials may have a long history in other fields of medicine, but are experiencing a transition into orthopaedic use. In contrast, evolving materials have an established history in the field of orthopaedic materials, but they are being processed in new ways to gain additional functionalities. This issue will explore both of these approaches and discuss how financial and regulatory burdens affect material technology development. A recent special issue has focused on the 3-dimensional printing of materials for orthopaedics so we will not discuss that innovation here. Dr Elsner and Dr McKeon have provided a thorough review on the use of polycarbonate urethanes, a material emerging from the cardiovascular field due to its enhanced oxidative stability compared with prior polyurethanes. Regarding orthopedic use, polycarbonate urethanes show a much softer response and less wear compared with ultra-high molecular weight polyethylene, thus this material is potentially replacing bearing surfaces in hip arthroplasty and being trialed as a meniscus replacement. This review covers the full spectrum of material development from in vitro biomechanics to animal testing to clinical outcomes. Dr Smith and colleagues describe the use of shape-memory polymers for soft-tissue fixation. The concept and use of shape-memory polymers has seen a long history since the 1960s as heat-shrink tubing, but only recently have they emerged into the Orthopaedic field due to advances in activation mechanisms. The principles of both shape-memory polymers and soft-tissue fixation mechanics are discussed as well as the advantages of these expandable devices. In addition, Dr Higgs gives an in-depth explanation of how to use shape-memory polymer devices for posterior lateral corner reconstruction, which greatly simplifies the procedure. Dr Lei and colleagues have written a comprehensive review on the use of dehydrated human amnion/chorion membranes allograft for healing Orthopaedic soft-tissues. Although amniotic membranes have been used for wound healing and skin grafting since the early 20th century, it is the refinement of processing methods and continued expansion into more Orthopaedic applications that drives the use of this regenerative technology. This review covers the relevant biological markers and components of these allografts along with a myriad of clinical uses, including rotator cuff repair, anterior cruciate ligament reconstruction, Achilles tendinopathy, plantar fasciitis, and even transforaminal lumbar interbody fusion. Torstrick and colleagues discuss the development of a porous PEEK interbody fusion device. PEEK interbody fusion devices have a history of producing a fibrous tissue response due to their smooth surface, but porous PEEK challenges this paradigm with its 3-dimensional topography that allows for osseointegration. Although the effect of chemical structure and topography on osseointegration is a current debate, this porous PEEK serves as an example of how altering topography can change the biological response to a well-known material. Dr Burkus and Dr Chappuis present clinical examples of their experience where the porous PEEK interbody fusion device was used for anterior cervical discectomy and fusion. Dr Bariteau and colleagues give a detailed review of the ethical, financial, and regulatory issues to be considered when developing a new orthopedic technology. The need for new technology is illustrated by the development of total hip arthroplasty devices throughout the 20th century. Innovation is necessary for improving patient care, and it must be done in the face of steep research and development costs and significant regulatory requirements. In addition, total ankle replacements are given as an example of recent technology development in the foot and ankle market. Finally, we would like to thank all of the authors for their time and contributions to this symposium.

* The Ovine Model for Meniscus Tissue Engineering: Considerations of Anatomy, Function, Implantation, and Evaluation.

Meniscus injuries represent one of the most-common intra-articular knee injuries. The current treatment options include meniscectomy and allograft transplantation, both with poor long-term outcomes. Therefore, there is a need for regenerative techniques to restore meniscal function. To preclinically test scaffolds for meniscus replacement, large animal models need to be established and standardized. This review establishes the anatomical and compositional similarities between human and sheep menisci and provides guidance for implantation and evaluation of such devices. The ovine meniscus represents a scaled-down version of the human meniscus, with only slight structural differences that can be addressed during device fabrication. Implantation protocols in sheep remain a challenge, as the meniscus cannot be visualized with the arthroscopic-assisted procedures commonly performed in human patients. Thus, we recommend the appropriate implantation protocols for meniscus visualization, ligamentous restoration, and surgical fixation of both total and partial meniscus replacement devices. Last, due to the lack of standardization in evaluation techniques, we recommend a comprehensive battery of tests to evaluate the efficacy of meniscus replacement implants. We recommend other investigators utilize these surgical and testing techniques to establish the ovine model as the gold standard for preclinical evaluation of meniscus replacement devices.

Clinical Studies Using Biological and Synthetic Materials for Meniscus Replacement.

Meniscal injury is a common problem among sportsmen and increasingly seen in the older and more active population. The traditional treatment options include a partial meniscectomy, which provides good mechanical and pain relief to the patient. However, the focus of treatment is shifting towards repairing meniscal tears where possible and replacement of the lost meniscal tissue where appropriate. Replacement can be total or partial. Total meniscal replacement using an allograft, is usually reserved for young patients, who meet certain criteria and who have undergone several subtotal meniscectomies or a single stage total meniscectomy and are still symptomatic. Partial meniscal replacement can be utilized in conjunction with a partial meniscectomy to fill the resulting space left by the resection. Collagen based implants and synthetic scaffolds have entered the European market but have demonstrated mixed results in clinical trials. Tissue engineering to create an implant that mimics the biomechanical properties holds much potential for future research.

Friction properties of a new silk fibroin scaffold for meniscal replacement

The menisci protect the articular cartilage by reducing contact pressure in the knee. To restore their function after injury, a new silk fibroin replacement scaffold was developed. To elucidate its tribological properties, friction of the implant was tested against cartilage and glass, where the latter is typically used in tribological cartilage studies. The silk scaffold exhibited a friction coefficient against cartilage of 0.056, which is higher than meniscus against cartilage but in range of the requirements for meniscal replacements. Further, meniscus friction against glass was lower than cartilage against glass, which correlated with the surface lubricin content. Concluding, the tribological properties of the new material suggest a possible long-term chondroprotective function. In contrast, glass always produced high, non-physiological friction coefficients.

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.

MR-Imaging of Meniscal Substitution.

More than a century ago, the menisci were considered to be the functionless remains of a leg muscle. Gradually the usefulness and function of the meniscus was investigated and proven, and the link between total meniscectomy, radiographic osteoarthritis and reduced knee function was made. Subsequently, partial meniscectomy was introduced in the clinical practice. However, the frequency of symptomatic knee osteoarthritis was not substantially lowered. Therefore, meniscal repair was introduced for younger individuals with traumatic meniscus lesions with a good healing potential. Later on in the development process, the quest for meniscal replacement strategies arose. The introduction of allogenic, xenogenic and artificial materials followed in research and clinical settings. Nowadays, a lot of research is conducted on meniscal substitutes, because meniscal injuries are a very common problem in the general population. The imaging of the meniscus is running parallel to this evolution. With the development of magnetic resonance imaging (MRI), the meniscus could be perfectly visualized. A lot of studies were published on imaging of the normal meniscus, and subsequently meniscal pathology on MRI was investigated. In the current literature, a growing number of papers describe the MRI findings in artificial meniscus replacements.

Negative Outcomes of Poly(l-Lactic Acid) Fiber-Reinforced Scaffolds in an Ovine Total Meniscus Replacement Model.

Our objective was to test the efficacy of collagen-hyaluronan scaffolds reinforced with poly(l-lactic acid) (PLLA) fibers in an ovine total meniscus replacement model. Scaffolds were implanted into 9 sheep (n = 1 at 8 weeks, n = 2 at 16 weeks, n = 3 at both 24, 32 weeks) following total medial meniscectomy. From 16 weeks on, explants were characterized by confined compression creep, histological, and biochemical analyses. Articular surfaces were observed macroscopically and damage was ranked histologically using the Mankin score. At sacrifice, three of the nine PLLA scaffolds had completely ruptured, and the intact scaffolds experienced progressive shape changes and severe narrowing in the body region at 16, 24, and 32 weeks. Aggregate compressive modulus and permeability did not improve with time. Histological and biochemical analyses showed significantly less extracellular matrix and less matrix organization compared to native tissue. Osteophytes, bone erosion, and cartilage damage were observed, increasing with time postimplantation. A buildup of lactic acid and/or the rapid loss of scaffold mechanical integrity due to PLLA degradation are probable causes for the joint abnormalities observed in this study. These results are in sharp contrast to those of our previous successful total meniscus replacement studies using polyarylate [p(DTD DD)] fiber-reinforced scaffolds. This suggests that PLLA fiber as produced in this study cannot be used as reinforcement for a meniscus replacement scaffold.

Knee Menisci.

The menisci of the knees are semicircular fibrocartilaginous structures consisting of a hydrophilic extracellular matrix containing a network of collagen fibers, glycoproteins, and proteoglycans maintained by a cellular component. The menisci are responsible for more than 50% of load transmission across the knee and increase joint congruity thereby also aiding in fluid film lubrication of the joint. In the United Kingdom, meniscal tears are the most common form of intra-articular knee injury and one of the commonest indications for orthopedic intervention. The management of these injuries is dependent on the location within the meniscus (relative to peripheral blood supply) and the pattern of tear. Removal of meniscus is known to place the knee at increased risk of osteoarthritis; therefore repair of meniscal tears is preferable. However, a significant proportion of tears are irreparable and can only be treated by partial or even complete meniscectomy. More recent studies have shown encouraging results with meniscal replacement in this situation, though further work is required in this area.

Physiologically Distributed Loading Patterns Drive the Formation of Zonally Organized Collagen Structures in Tissue-Engineered Meniscus.

The meniscus is a dense fibrocartilage tissue that withstands the complex loads of the knee via a unique organization of collagen fibers. Attempts to condition engineered menisci with compression or tensile loading alone have failed to reproduce complex structure on the microscale or anatomic scale. Here we show that axial loading of anatomically shaped tissue-engineered meniscus constructs produced spatial distributions of local strain similar to those seen in the meniscus when the knee is loaded at full extension. Such loading drove formation of tissue with large organized collagen fibers, levels of mechanical anisotropy, and compressive moduli that match native tissue. Loading accelerated the development of native-sized and aligned circumferential and radial collagen fibers. These loading patterns contained both tensile and compressive components that enhanced the major biochemical and functional properties of the meniscus, with loading significantly improved glycosaminoglycan (GAG) accumulation 200-250%, collagen accumulation 40-55%, equilibrium modulus 1000-1800%, and tensile moduli 500-1200% (radial and circumferential). Furthermore, this study demonstrates local changes in mechanical environment drive heterogeneous tissue development and organization within individual constructs, highlighting the importance of recapitulating native loading environments. Loaded menisci developed cartilage-like tissue with rounded cells, a dense collagen matrix, and increased GAG accumulation in the more compressively loaded horns, and fibrous collagen-rich tissue in the more tensile loaded outer 2/3, similar to native menisci. Loaded constructs reached a level of organization not seen in any previous engineered menisci and demonstrate great promise as meniscal replacements.

Regeneration of knee joint menisci – methods review

Abstract At present, there is no need to convince anyone that menisci are crucial structures dealing with a huge number of responsibilities, and its absence in a knee joint results in irretrievable chondral damage. A lot of methods have been recently developed to treat meniscal tears: physical therapy as a first and, for some cases, a last step, bonding by biodegradable sutures, screws, or arrows, collagen and polyurethane scaffolds designed for partial meniscus replacement, and finally allograft transplantation. However, all of them have numerous limitations and can be used in specific conditions only. That is the reason why partial and total meniscectomy is up to this time a common operation in the case of degenerative or complex meniscus tears despite its well-known degenerative consequences. Trials to overcome those limitations are ongoing, and the challenge to invent a long-term successful regeneration method or to design a substitute that well mimics an anatomical meniscus is still in front of us.

The role of meniscal tissue in joint protection in early osteoarthritis.

It is widely accepted that partial meniscectomy leads to early onset of osteoarthritis (OA). A strong correlation exists between the amount and location of the resected meniscus and the development of degenerative changes in the knee. On the other hand, osteoarthritic changes of the joint alter the structural and functional integrity of meniscal tissue. These alterations might additionally compromise the limited healing capacity of the meniscus. In young, active patients without cartilage damage, meniscus therapy including partial meniscectomy, meniscus suture, and meniscus replacement has proven beneficial effects in long-term studies. Even in an early osteoarthritic milieu, there is a relevant regenerative potential of the meniscus and the surrounding cartilage. This potential should be taken into account, and meniscal surgery can be performed with the correct timing and the proper indication even in the presence of early OA.

Mechanical Integrity of a Decellularized and Laser Drilled Medial Meniscus

Since the meniscus has limited capacity to self-repair, creating a long-lasting meniscus replacement may help reduce the incidence of osteoarthritis (OA) after meniscus damage. As a first step toward this goal, this study evaluated the mechanical integrity of a decellularized, laser drilled (LD) meniscus as a potential scaffold for meniscal engineering. To evaluate the decellularization process, 24 porcine menisci were processed such that one half remained native tissue, while the other half was decellularized in sodium dodecyl sulphate (SDS). To evaluate the laser drilling process, 24 additional menisci were decellularized, with one half remaining intact while the other half was LD. Decellularization did not affect the tensile properties, but had significant effects on the cyclic compressive hysteresis and unconfined compressive stress relaxation. Laser drilling decreased the Young's modulus and instantaneous stress during unconfined stress relaxation and the circumferential ultimate strength during tensile testing. However, the losses in mechanical integrity in the LD menisci were generally smaller than the variance observed between samples, and thus, the material properties for the LD tissue remained within a physiological range. In the future, optimization of laser drilling patterns may improve these material properties. Moreover, reseeding the construct with cells may further improve the mechanical properties prior to implantation. As such, this work serves as a proof of concept for generating decellularized, LD menisci scaffolds for the purposes of meniscal engineering.

Comparing the mechanical properties of the porcine knee meniscus when hydrated in saline versus synovial fluid

As research progresses to find a suitable knee meniscus replacement, accurate in vitro testing becomes critical for feasibility and comparison studies of mechanical integrity. Within the knee, the meniscus is bathed in synovial fluid, yet the most common hydration fluid in laboratory testing is phosphate buffered saline (PBS). PBS is a relatively simple salt solution, while synovial fluid is a complex non-Newtonian fluid with multiple lubricating factors. As such, PBS may interact with meniscal tissue differently than synovial fluid, and thus, the hydration fluid may be an important factor in obtaining accurate results during in vitro testing. To evaluate these effects, medial porcine menisci were used to evaluate tissue mechanics in tension (n=11) and compression (n=15). In all tests, two samples from the same meniscus were taken, where one sample was hydrated in PBS and the other was hydrated in synovial fluid. Statistical analysis revealed no significant differences between the mean mechanical properties of samples tested in PBS compared to synovial fluid; however, compressive testing revealed the variability between samples was significantly reduced if samples were tested in synovial fluid. For example, the compressive Young׳s Modulus was 12.69±7.49MPa in PBS versus 12.34±4.27MPa in synovial fluid. These results indicate testing meniscal tissue in PBS will largely not affect the mean value of the mechanical properties, but performing compression testing in synovial fluid may provide more consistent results between samples and assist in reducing sample numbers in some experiments.

Tissue engineering of the meniscus: Scaffolds for meniscus repair and replacement

The menisci homogenously distribute load throughout the knee joint. Partial or total removal of the menisci significantly alters the biomechanical properties of the knee, leading to osteoarthritis and articular cartilage (AC) degeneration. Many synthetic and natural materials have been tested to find a scaffold that can withstand the natural mechanical forces on the joint. However, currently there are few meniscus tissue (MT) replacements available for clinical use. This review addresses tissue engineering (TE) of the meniscus, with a primary focus on tissue engineered scaffolds (TESs) as current and future models for meniscus replacement. Our review also discusses implant fixation, an area which we believe must be improved in order for meniscal replacements to be successful in vivo.

Association of a hi-tech with a bio-tech technique in the treatment of early osteoarthritis of the knee: a case report.

Meniscal replacement to treat early osteoarthritis of the knee after meniscectomy may be accompanied by other surgical procedures to treat factors predisposing to a negative intervention outcome. Overload of the medial compartment in slight varus can be reduced by applying the new KineSpring system, which can promote the best possible outcome of a biodegradable meniscal scaffold implantation, without producing biomechanical and anatomical alterations of the joint. This is the first case report on the combination of these hi-tech and bio-tech techniques.

Clinical Application of Scaffolds for Partial Meniscus Replacement.

Meniscal tears are common injuries often treated by partial meniscectomy. This may result in altered joint contact mechanics which in turn may lead to worsening symptoms and an increased risk of osteoarthritis. Meniscal scaffolds have been proposed as a treatment option aimed at reducing symptoms while also potentially reducing progression of degenerative change. There are 2 scaffolds available for clinical use at the present time; Collagen Meniscus Implant and Actifit. Medium-term to long-term data (4.9 to 11.3 y) demonstrate efficacy of partial meniscus replacement. The patients who seem to benefit most are chronic postmeniscectomy rather than acute meniscal injuries. Herein we report on available clinical data for Collagen Meniscus Implant and Actifit while describing our preferred surgical technique and postoperative rehabilitation program.

Successful Total Meniscus Reconstruction Using a Novel Fiber-Reinforced Scaffold

Background: Meniscus injuries in the United States result in an estimated 850,000 surgical procedures each year. Although meniscectomies are the most commonly performed orthopaedic surgery, little advancement has been made in meniscus replacement and regeneration, and there is currently no total meniscus replacement device approved by the Food and Drug Administration. Hypothesis: A novel fiber-reinforced meniscus scaffold can be used as a functional total meniscus replacement. Study Design: Controlled laboratory study. Methods: A tyrosine-derived, polymer fiber–reinforced collagen sponge meniscus scaffold was evaluated mechanically (tensile and compressive testing) and histologically after 16 and 32 weeks of implantation in an ovine total meniscectomy model (N = 20; 16 implants plus 4 meniscectomies, divided equally over the 2 time periods). The extent of cartilage damage was also measured on tibial plateaus by use of toluidine blue surface staining and on femoral condyles by use of Mankin scores on histological slides. Results: Scaffolds induced formation of neomeniscus tissue that remained intact and functional, with breaking loads approximating 250 N at both 16 and 32 weeks compared with 552 N for native menisci. Tensile stiffness values (99 and 74 N/mm at 16 and 32 weeks, respectively) were also comparable with those of the native meniscus (147 N/mm). The compressive modulus of the neomeniscus tissue (0.33 MPa at both 16 and 32 weeks) was significantly increased compared with unimplanted (time 0) scaffolds (0.15 MPa). There was histological evidence of extensive tissue ingrowth and extracellular matrix deposition, with immunohistochemical evidence of types I and II collagen. Based on significantly decreased surface damage scores as well as Mankin scores, the scaffold implants provided greater protection of articular cartilage compared with the untreated total meniscectomy. Conclusion: This novel fiber-reinforced meniscus scaffold can act as a functional meniscus replacement, with mechanical properties similar to those of the native meniscus, while protecting the articular cartilage of the knee from the extensive damage after a total meniscectomy. Clinical Relevance: This meniscus replacement scaffold has the potential to improve surgical treatment and provide better long-term outcomes for those suffering from severe meniscus damage.

Meniscal Scaffolds - Preclinical Evidence to Support their Use: A Systematic Review.

Arthroscopic meniscal treatment is the most common procedure performed in the orthopedic practice. Current management of meniscal pathology relies on different therapeutic options, ranging from selective meniscectomy, suturing, and to meniscal replacement by using either allografts or scaffolds. The progresses made in the field of regenerative medicine and biomaterials allowed to develop several meniscal substitutes, some of those currently used in the clinical practice. Before reaching the clinical application, these devices necessarily undergo accurate testing in the animal model: the aim of the present manuscript is to systematically review the scientific evidence derived by animal model results for the use of meniscal scaffolds, in order to understand the current state of research in this particular field and to identify the trends at preclinical level that may influence in the near future the clinical practice.Thirty-four papers were included in the present analysis. In 12 cases the meniscal scaffolds were used with cells to further stimulate tissue regeneration. With the exception of some negative reports regarding dacron-based scaffolds, the majority of the trials highlighted that biomaterials and bio-engineered scaffolds are safe and could play a beneficial role in stimulating meniscal healing and in chondral protection. With regard to the benefits of cell augmentation, the evidence is limited to a small number of studies and no conclusive evidence is available. However, preclinical evidence seems to suggest that cells could enhance tissue regeneration with respect to the use of biomaterials alone, and further research should confirm the translational potential of cell-based approach.

Functional biomechanical performance of a novel anatomically shaped polycarbonate urethane total meniscus replacement.

PurposeTo evaluate the functional biomechanical performance of a novel anatomically shaped, polycarbonate urethane total meniscus implant.MethodsFive human cadaveric knees were flexed between 0° and 90° under compressive loads mimicking a squat movement. Anteroposterior (AP) laxity tests were performed in 30° and 90° flexion. Meniscal kinematics and knee laxity were quantified using roentgen stereophotogrammetric analysis. Tibial cartilage contact mechanics were determined in 90° flexion. Measurements were repeated for the native medial meniscus, the implant, after total medial meniscectomy and allograft transplantation.ResultsThe implant and allograft displayed increased posterior and medial displacements compared to the native meniscus, yet no differences were found between the implant and allograft. Meniscal condition did not affect rotational laxity. Compared to the native joint, AP laxity for the implant was increased in 30° flexion, but not in 90°. The implant reduced the mean contact pressure compared to meniscectomy but could not restore contact pressures to native meniscus levels. Compared to the native meniscus, the implant significantly increased the peak pressure, while the contact area was reduced. Contact mechanics of the implant and allograft were never statistically different.ConclusionsBiomechanical performance was similar for the implant and allograft. However, both meniscal replacements could not restore outcomes to native meniscus levels or sufficiently improve outcomes after meniscectomy. This was presumably caused by the mobility allowed by the suture-only horn fixation. The similarity of implant and allograft performance suggests that the novel implant has the biomechanical potential to serve as an alternative to meniscal allograft transplantation.