The meniscus is a crucial player in knee joint homeostasis. Loss of meniscus tissue can result in early onset of clinical symptoms like pain and loss of function, and structural degeneration of the articular cartilage. In case of a symptomatic segmental defect of the medial or lateral meniscus, different innovative options using biological or synthetic scaffolds are now available to regenerate meniscuslike tissue, with the aim of allowing a satisfactory clinical improvement to patients. However, the role of any of these procedures in terms of chondroprotection is questionable, and the overall outcomes in the long term still can be improved.
Meniscus scaffolds represent a safe and viable treatment for symptomatic partial meniscus defects in the well-aligned, stable knee with limited cartilage degeneration.
Meniscus scaffolds provide significant improvement of clinical outcome at short and midterm follow-up, with an acceptable failure rate and complication rate.
In most cases, MRI shows a reduced size of the implant, with hyperintense signal. The clinical relevance remains unclear.
The chondroprotective effect of meniscus scaffolds remains to be proven.
Meniscectomy is one of the most common procedures in orthopedic surgery, capable of returning the knee to a satisfactory function when a meniscal tear occurs. However, over the years, several concerns have arisen about its detrimental effects on the joint status in the medium to long term. It is now acknowledged that loss of meniscal tissue permanently alters knee biomechanics and homeostasis with secondary degenerative changes to the articular cartilage and higher risk of developing symptomatic osteoarthritis (OA). Hence, meniscus repair and substitution have gained significant interest. Unfortunately, the effectiveness of meniscal repair strictly relies on the tissue quality and defect location with respect to the vascular supply; tears in the vascularized “red” peripheral zone are more likely to heal, whereas the more common lesions in the avascular “white” zone have poor healing potential. Unfortunately, meniscectomy is unavoidable in more than 90% of cases.
In the past decades, alternative meniscus substitution strategies have been developed to replace symptomatic loss of meniscal tissue. Meniscal allograft transplantation and meniscus prostheses have been used to replace a complete or subtotal loss of meniscal substance, whereas scaffolds have been developed for segmental meniscus defects. Meniscus allograft transplantation is a well-established procedure with extensive literature highlighting the results for long-term follow-up. However, the role and indication of a meniscus scaffold for the biological treatment of a segmental defect remain more controversial. The general goal is to save or replace the damaged meniscal tissue with the final goal to provide early pain relief, healing of the damaged or absent tissue, and prevention of secondary joint degeneration in the long term. The effectiveness of scaffolds in terms of clinical improvement and chondroprotection still can be improved. This narrative review aims at highlighting the current state of meniscus scaffold surgery and the advancements being made.
General Concept of the Meniscus Scaffold
Meniscus scaffolds are 3-dimensional biocompatible structures capable of supporting meniscuslike fibrocartilaginous tissue regeneration in segmental meniscus defects ( Fig. 1 ). Two constructs for meniscal replacement are available on the market: the first is made of bovine collagen derived from purified bovine Achilles tendon with collagen fibers enriched with glycosaminoglycans to aid cellular ingrowth. The scaffold is highly bioresorbable (12–18 months) and highly porous (collagen meniscus implant [CMI]; Stryker, Kalamazoo, MI). The second more recent scaffold consists of a synthetic polyurethane-based material with flexible segments made from polycaprolactone 80% and stiff segments made from urethane 20% (Actifit; Orteq Sports Medicine, London, UK). The scaffold is slowly biodegradable with an estimated degradation time of 4 to 6 years and is highly porous. Both implants come in a specific configuration for medial or lateral meniscus defects.
Indications and Contraindications
Meniscus scaffold implantation represents a novel biological solution for the treatment of patients with symptomatic partial meniscus defects with limited signs of cartilage degeneration. Since the negative impact of meniscectomy in anterior cruciate ligament (ACL)-injured knees on long-term cartilage degeneration has recently been established, prophylactic meniscus reconstruction using a scaffold in the ACL reconstructed knee with partial meniscectomy could be another indication.
The key inclusion criteria are (1) irreparable medial or lateral meniscal tear or partial meniscus loss with intact rim. The meniscus substitute is not intended for the treatment of total or subtotal meniscus defects; ideally, the defect length should be limited to 5 to 6 cm; (2) skeletally mature patients; (3) age 16 to 50 years; (4) stable knee joint or knee joint stabilization procedure within 12 weeks of index procedure; and (5) International Cartilage Repair Society (ICRS) classification ≤3.
The key exclusion criteria are (1) total meniscus loss or unstable segmental rim defect; (2) multiple areas of partial meniscus loss that could not be treated by a single scaffold; (3) any significant malalignment (varus or valgus); (4) ICRS classification greater than 3; and (5) body mass index ≥35. Of importance, the presence of condylar squaring, a structural phenomenon often observed years after meniscectomy, is to be considered a contraindication, as it becomes structurally impossible to introduce a triangular-shaped scaffold into a flattened joint line.
The surgical technique is similar for both the devices, involving the arthroscopic resection of the damaged tissue and subsequent implantation of a custom-sized, porous material, which is finally sutured to the meniscal rim and capsule using standard inside-out, outside-in, or all-inside sutures. A partial meniscectomy with surgical debridement back to the vascularized zone of the damaged portion of the meniscus is performed. The meniscus rim should be continuous, this is of particular importance to the popliteal hiatus of the lateral meniscus. In this area, a complete loss of the tissue in front of the popliteus tendon is often referred to as a partial defect but should be considered a total loss and is therefore a contraindication for a meniscus scaffold. After debridement, the resulting void is measured for sizing along the peripheral edge using the meniscal ruler guide and ruler supplied with the scaffold. The scaffold is cut to fit and using a blunt-nosed grasper, placed into the knee joint through the anteromedial or anterolateral portal and sutured to the native meniscus. The suturing techniques used are all-inside, inside-out, or outside-in depending on the area to be sutured and the surgeon’s experience and preference.
Histologic evidence of tissue ingrowth and regrowth remains scarce. The first clinical article describing histology after CMI was published in 2008 by Rodkey and colleagues. Based on the histologic evaluations performed 1 year after implantation, the collagen meniscus implant appears to provide a scaffold for the formation of hybrid fibrous and meniscuslike fibrochondrocytic matrix by the host. In nearly all cases in which remnants of the CMI could be identified, there was evidence of infiltration into the interstices of the CMI with maturing fibrous connective tissue differentiating toward meniscuslike fibrochondrocytic tissue. All of these cases demonstrated some degree of assimilation of the CMI into a newly developing fibrochondrocytic matrix. Visual estimates indicated that approximately 10% to 25% of the CMI remained at 1 year. An incidental, rare finding (observed in <5% of the cases) was inflammation of the synovium in the biopsy specimen of the CMI, but none of these cases was associated with any clinical findings of synovitis at the time of the second-look arthroscopy.
An early publication 1 year after implantation of the polyurethane scaffold showed fully vital material with no signs of inflammatory reaction, necrosis, or cell death, illustrating that the scaffold is biocompatible and supports successful new tissue ingrowth. Moreover, a distinct organization of tissue was observed, with 3 layers based on the presence or absence of vessel structures, cellular morphology, and extracellular matrix (ECM) composition. This particular organization with vascular and avascular tissue with a collagenous matrix resembles that of native human meniscus tissue. When comparing the biopsy findings of the inner free edge of the scaffold-meniscus with the native meniscus tissue, layer 1 resembles the peripheral red, vascularized zone typically rich in meniscus cells of the fusiform (fibroblastlike) cell type and thus rich in type I collagens. Layer 2 resembles the middle red-white zone of the native human meniscus containing a mixture of oval and polygonal fibrochondroblastlike cells and fibroblastlike cells while being completely avascular. Layer 3 resembles the white or inner third zone with fibrochondroblastlike cells, characterized by its avascularity; nevertheless, the observed ECM is still immature. This characteristic organization suggests that ingrowth is started superficially and that a maturation process occurs in an inbound direction. It should be noted, however, that fully mature meniscuslike tissue was not observed at the 12-month time-point. These clinical histologic results are supportive of data previously reported in animal studies that describe an active fibrovascular ingrowth derived from the synovium following total meniscal replacement with the meniscus implant. Over time, this fibrovascular front slowly retracted, leaving behind tissue that resembled fibrocartilage within the scaffold.
A recent comparative study reported that biopsy samples from the CMI group showed more fibrous tissue that was rich in spindle and rounded fibroblastlike cells and blood vessels. The Actifit biopsy samples appeared completely avascular with more cartilaginouslike appearance consisting of chondroblastlike roundish, large, and active cells. Over time, there was a greater percentage of smaller cells that had completely differentiated into chondrocytes, surrounded by a capsule and inserted in gaps, with few cells displaying a typical columnar arrangement. All the biopsy samples showed vital cell and matrix structures with no evidence of necrosis. In 3 of the 11 Actifit patients who underwent second-look arthroscopy, histologic evaluation showed presence of plasma cells, macrophages, and rare lymphocytes, which could be a result of foreign body reaction.
Both implants, either based on collagen or polyurethane, showed promising short-term clinical results and stable satisfactory outcomes up to midterm and long-term evaluation. Clinical follow-up studies report outcomes for CMI ranging from 6 months to 12 years, whereas the longest clinical follow-up study on Actifit reports up to 8 years. Overall, significant improvement has been documented in all studies using a wide range of clinical outcome scores: Lysholm, Visual Analog Scale (VAS) pain, International Knee Documentation Committee (IKDC), Tegner, Knee injury and Osteoarthritis Outcome Score (KOOS), Cincinnati, a patient self-assessment scale and a satisfaction scale, EuroQol (EQ)-5D, Knee Society Score (KSS), University of California Los Angeles, Short Form (SF)-36, and an activity scale. Typically, patients will progressively improve over the first year with an approximate improvement of 30 points on Lysholm (maximum 100) and 3.5 points on the VAS score (maximum 10). These clinical results remain stable over time, although few studies report long-term clinical outcomes. Monllau and colleagues reports 83% good and excellent results at 10-year follow-up for 22 patients treated with the CMI device. The typical 30 points improvement of the Lysholm score was present, improving from 59.9 (range, 30–90) to 89.6 (range, 78–100; P <.001) and 87.56 (range, 59–100; P <.001) at 1-year and 10-year follow-up, respectively. A significant improvement of all the clinical scores from preoperative status to final follow-up (9.6 years mean follow-up) was reported by Bulgheroni and colleagues in a randomized trial aiming to compare the clinical, objective, and radiographic long-term results of patients with ACL rupture and partial medial meniscus defects treated with ACL reconstruction and partial medial meniscectomy or medial CMI implant. Even if all the clinical scores increased over time, no statistically significant differences were found between these 2 groups. Zaffagnini and colleagues report results in a prospective study evaluating patients treated with medial CMI implantation versus partial medial meniscectomy. The CMI group showed significantly lower VAS for pain, higher objective IKDC, and Tegner scores compared with the meniscectomy group at minimum 10-year follow-up. The SF-36 and Lyshom scores did not show a statistically significant differences between both groups. A recent meta-analysis on 613 Actifit patients reports that both VAS and Tegner scores improved significantly and remained stable up to 72 months. This suggests that stabilization of the pain allows activity level to remain unchanged over time. Schüttler and colleagues report on 18 Actifit patients with a follow-up of 4 years demonstrating significant improvement of VAS from 5 preoperatively to 1 at 4 years of follow-up. In a similar study by Leroy and colleagues with a minimal follow-up of 5 years, 15 patients improved from 5.3 and 50 preoperative VAS and subjective IKDC scores respectively to 2.9 and 79 at a mean follow-up of 6 years (range 5–8 years). Another recent meta-analysis by Houck and colleagues showed similar clinical outcome for both CMI and Actifit patients. The preoperative status of cartilage damage is proven to affect the clinical outcomes, irrespective of the type of scaffold used. It has been proven that cartilage damage should not exceed ICRS grade 2 to obtain predictable results after meniscal implantation.
Scaffold implantation along with concomitant procedures does not influence clinical outcome, and often implicates a slower recovery. Some investigators therefore do not recommend to proceed to combine surgeries, such as ACL reconstruction or high tibial osteotomies. It is still debated whether patients with an acute lesion or those with a chronic lesion (previous surgeries in the treated knee) have better results. These controversial findings can be explained by the rapid clinical improvement offered by a simple meniscectomy, but current evidence tends to support the use of meniscal scaffolds for chronic lesions, with better clinical outcomes at longer follow-up. A small number of complications has been reported with a total rate of 12.6%. These include pain, effusion, infections, suture removals, debridement of nonintegrated scaffold, tear of tissue scaffold, nerve branch included in a suture, and excessive scar tissue formation. Failures are variously defined in each article, going from infection due to the implant, mechanical blocking, or chronic synovitis. Most investigators consider a failure any unplanned second operation on the index knee including but not limited to implant removal, osteotomies, and total joint arthroplasty. The lack of a commonly accepted definition of failure makes a comparison of failed patients among different studies very difficult and a meaningful analysis impossible. Failure rates have been described to increase over time defined by progression of the osteoarthritic disease or pain, with a comparable reported rate of 9.9% at a mean follow-up of 40 months and 6.7% at a mean follow-up of 44 months, for the Actifit and CMI patients, respectively.
Only a few articles reporting the MRI results of meniscal scaffolds have been published, and even fewer investigators have reported the long-term MRI outcomes of these procedures ( Figs. 2 and 3 ). The Genovese classification is the most commonly used classification to evaluate the scaffold quality by means of morphology/size and signal intensity, despite low interobserver and intraobserver reliability. Generally, a reduction in size of the scaffold is found, with a persistency of signal hyperintensity. This hyperintense signal tends to diminish over the years showing scaffold maturation, cellular ingrowth, and collagen network creation, but never reaches the same low signal of the normal fibrocartilaginous meniscus. These MRI findings have raised several concerns despite their clinical significance remaining unclear. Patients receiving CMI scaffolds had higher grades for Genovese morphology and signal intensity when compared with Actifit scaffold patients. On MRI, extrusion is more frequently observed in the Actifit-treated patients with no defined correlation with clinical outcomes. These data are reported in a recent meta-analysis by Young-Soo Shin, where despite a worsening cartilage status and meniscal extrusion between baseline and final follow-up was found, patients demonstrated significant functional improvement and pain relief when compared with baseline scores. Moreover, preoperative coronal meniscal extrusion strongly predicts postoperative clinical and morphologic outcomes. Therefore, absence of such extrusion at preoperative MRI should be added as a criterion for patient selection for meniscal scaffold implantation. In patients with post-partial-meniscectomy syndrome and a sufficiently thick meniscal rim, the possibility that a meniscal allograft may be more appropriate than a substitute should be considered. No significant progression of the degenerative process is found at short-term and midterm follow-up according to the ICRS or the Outerbridge scores. These results are confirmed at longer-term follow-up up to 10 years with radiographic evaluation demonstrating no development or progression of degenerative knee joint disease. Significantly less medial joint space narrowing was found in the CMI group compared with the meniscectomy controls in only one comparative study by Zaffagnini and colleagues. However, study limitations do not allow clear conclusions to be drawn on the chondroprotective effects of the newly formed meniscus.