Articular Cartilage Lesions


Articular cartilage lesions are a key concern in orthopaedic surgery because cartilage has an extremely poor capacity to heal. Treatment of these lesions aims to restore an articular surface that matches the biomechanical properties of normal hyaline cartilage and to prevent the progression of focal cartilage injury to end-stage arthritis.

A cartilage defect has a very limited ability to recover spontaneously due to its unique characteristics. It is avascular, aneural, alymphatic, and composed of just one cell type—the chondrocyte. That is why no surgical technique has ever been completely successful in stimulating articular cartilage repair and regeneration. Conventional surgical techniques to repair cartilage defects such as microfracture or drilling lead to poor subchondral bone regeneration and fibrocartilage tissue, thus mechanical competence and structural organization is significantly inferior to hyaline cartilage. Osteochondral transfers are viable options as well and attention continues toward the development of biological methods such as third-generation autologous chondrocyte implantation (ACI) to enhance regeneration of native cartilage, to decrease the degenerative condition of joints, and improve clinical outcomes.

Besides the biology of cartilage repair techniques, improved outcomes after cartilage repair depend on the patient and lesion-specific variables such as age and comorbidities, as well as location, size, and chronicity of lesion and concomitant pathologies of the affected knee.

The purpose of this chapter is to review the clinical evaluation of articular cartilage lesions and summarize the current treatment modalities for the management of these injuries. Subsequently, we will discuss our preferred methods in more detail.

Relevant Anatomy and Biomechanics

Articular cartilage is highly specialized tissue and provides a bearing surface with a minimum-low friction. Due to absence of vascular, neural, and lymphatic components, articular cartilage has a limited capacity for self-repair. It has been generally accepted that partial-thickness defects/injuries, which do not penetrate subchondral bone, are not repaired by the body, whereas those that extend past the depth of the subchondral plate initiate migration of marrow cells to fill the defect with a predominance of fibrocartilage. Unfortunately, fibrocartilage has inferior biomechanical properties and eventually progresses to symptomatic degeneration at the defect size.

Symptomatic articular cartilage lesions of the knee encompass a growing burden to the daily practice of orthopaedic surgeons. Curl et al. reviewed 31,516 knee arthroscopies and found that articular cartilage lesions were encountered in at least 1 of every 100 knee arthroscopies. Another large study reported similar findings after reviewing 25,124 knee arthroscopies and found that chondral lesions existed in 60% of the patients. In consecutive knee arthroscopy series, focal chondral or osteochondral defects were found in 11% to 19% of the patients. The medial femoral condyle and the patellar articular surface were the most frequent localization of the cartilage lesions with an average defect area of 2.1 cm. It has been suggested that patients under the age of 40 years may benefit more than older patients after cartilage repair surgeries. Patients under the age of 40 with localized high-grade chondral lesions comprised of 5% to 11% of all analyzed patients in these large series. Although the natural history of these defects is largely unknown, several studies showed that, if left untreated, these defects caused a deterioration in the affected knee and may progress to symptomatic degeneration of the joint.

Damage to the articular cartilage occurs for a variety of reasons, including chronic mechanical overload, developmental or genetic predisposition, and traumatic impact.

Trauma is one of the most common inciting events for cartilage injury with 61% of patients who underwent knee arthroscopy relating their current knee problem to a previous trauma. The majority of lesions are found concomitantly with meniscal and anterior cruciate ligament (ACL) injuries. Additionally, mechanical malalignment of the extremity and maltracking of the patella may lead to or aggravate cartilage defects when they both occur within the same joint. So before undertaking a cartilage repair procedure, condition of the menisci and ligaments, instability of patella, and alignment of the extremity must be considered regardless of the chondral defect treatment technique.

It is obvious that restoration of a neutral biomechanical environment is the single most important factor for the success of any cartilage repair procedure. In normal knee alignment, the medial compartment bears more than 60% of the physiologic load and in flexion an increasing amount of stress is transmitted through the medial side. Furthermore varus malalignment of the lower extremity disrupts this load distribution and even a 4% to 6% increase in varus malalignment increases the load in the medial compartment by up to 20%. In a cadaveric model it has been demonstrated that loading is nearly equally distributed between the medial and lateral compartments for alignments of 0 degrees to 4 degrees of valgus. Achieving more valgus after osteotomy results in unloading of the entire medial compartment; however, athletes and high-demand patients cannot tolerate such degrees of overcorrection. Therefore when performed simultaneously with cartilage repair procedures, osteotomy should restore neutral alignment rather than overcorrection.

If patellar or trochlear lesions occur with patellar maltracking or instability, these extensor mechanism pathologies should be corrected prior to or concomitantly with the cartilage repair procedures. In a similar concept, patellar malalignment or maltracking with an increased Q angle can lead to overloading of the lateral cartilage and increase the contact pressures. With tibial tubercle osteotomies, realignment of the extensor mechanism and relief of patellofemoral contact stresses can be achieved. A distal realignment with anteromedialization of the tibial tubercle by 10 mm can reduce the pressure applied to lateral patellar cartilage without overloading medial cartilage. Recently a systematic review was performed to determine whether a difference exists in outcomes of combined ACI and osteotomy versus isolated ACI with a minimum 2 years follow-up. Both groups showed improvements but when individual studies were compared, significantly greater clinical outcomes in subjects undergoing ACI combined with osteotomy were observed.

A high incidence of articular cartilage lesions associated with ACL injuries is well recognized, where the chondral injury is attributed to the actual, acute traumatic ACL injury. Articular cartilage is exposed to high shear forces either from the initial trauma to the knee or due to chronic instability secondary to the ACL tear. An increased risk of cartilage degeneration over the medial tibial plateau and patella has been shown if this ligamentous disruption is not treated properly. Furthermore, several studies have reported increasing incidence and severity of cartilage lesions with a delay in ACL reconstruction. This highlights the importance of ligament stability in patients undergoing cartilage repair procedures regardless of the technique used.

The knee meniscus protects the articular cartilage by both increasing the joint congruity and contact area and preventing the focal concentration of stresses. Complete or partial loss of a meniscus can have deleterious effects on a cartilage leading to a progression of osteoarthritis. Therefore meniscal repair should be the preferred option for patients with a meniscal lesion. Unfortunately, meniscectomy is unavoidable in the lesions that are not amenable to repair. In selected symptomatic patients with previous total or subtotal meniscectomy, meniscal transplantation can be a viable treatment option. Indications for meniscal transplantation are still being defined and the ideal candidate should be a young patient with joint line pain correlated with previous meniscectomy in a well-aligned and stable knee. Despite the fact that meniscal allograft transplantation is utilized as a salvage procedure in a majority of studies, the reported early and midterm results after meniscal allograft transplantations are encouraging with a survival rate of 75% to 87.8% at 5 years. Furthermore, when combined with articular cartilage repair procedures, improvements in both objective and subjective outcome measures were comparable to results of these procedures performed in isolation. However, there is insufficient literature reporting on the long-term outcomes of allograft meniscal transplantation. In a recently published prospective study high rates of failure have been detected due to deleterious remodeling of allograft. Authors suggested that preoperatively, patients should be counseled about the need for potential additional surgeries in the future given these findings.

Classification

With regard to the macroscopic evaluation of the cartilage surface, routinely performed at the time of surgery by arthroscopic or open means, the two most commonly used cartilage classification systems are the Outerbridge and International Cartilage Repair Society (ICRS) ( Table 96.1 ). Different from radiographic classifications, which are numerous, these two classification systems standardize and take into account the ability of the surgeon to physically palpate the chondral surface and grade the cartilage quality.

TABLE 96.1
Classification Systems for Cartilage Lesions
Grade of Lesion Outerbridge Classification ICRS Classification (With Subclassifications)
Grade 0 Normal cartilage Normal cartilage
Grade 1 Cartilage with softening and swelling
  • (a)

    Softening or fibrillations

  • (b)

    Superficial fissuring

Grade 2 Partial-thickness defect with fissures on the surface that do not reach subchondral bone or exceed 1.5 cm in diameter Less than one-half cartilage depth
Grade 3 Fissuring to the level of subchondral bone in an area with a diameter more than 1.5 cm More than one-half cartilage depth

  • (a)

    Not to the calcified layer

  • (b)

    To the calcified layer

  • (c)

    To the subchondral bone

  • (d)

    Blisters

Grade 4 Exposed subchondral bone Osteochondral lesion violating the subchondral plate
ICRS , International Cartilage Repair Society.
Excerpt from Farr J, Gomoll AH. Cartilage Restoration: Practical Clinical Applications . New York, NY: Springer-Verlag; 2013:42, Table 4.1.

History

Many times, distinct differences exist with the patient's presentation of focal chondral lesions and more global knee chondromalacia and arthrosis. Careful listening to the patient's descriptive history can provide guidance as to the potential underlying pathology. Whether it is the timeline of symptom onset, a recounting of previous traumatic injury, or even the detailing of prior surgical procedures, all of these details can provide important information. Activity-related pain in the knee with associated swelling, and possibly focal throbbing and aching after cessation of the activity, is commonly reported. This can be more pronounced with higher-impact activity such as sports participation and running and less noticeable with low impact-activities such as walking. Large chondral defects with associated displaceable flaps or even unstable chondral segments with associated loose bodies can become interposed within the joint surfaces, thus not only causing pain but also progressive damage to other initially uninvolved cartilage segments. These symptoms could also manifest as mechanical locking, giving way, crepitus, and sharp, lancinating pain.

Physical Examination

Just as it is absolutely paramount to listen to the patient's history to guide a thought process as to the potential etiology and chronicity of their presenting pathology, it is also just as important to carefully perform a physical exam to elicit even the most-subtle of physical exam findings. Many times, this can help guide your treatment regimen even prior to considering additional diagnostic imaging if indicated. Unless in an acute presentation, an acute hemarthrosis is unlikely. Typical findings can include mild soft tissue swelling with variable joint effusion size, joint line tenderness upon palpation and possible focal tenderness to the femoral condyle or patellar facets, possible varus/valgus pseudo-laxity depending upon how much unicompartmental chondral loss is present, standing varus or valgus malalignment, positive findings for patellar maltracking of J sign or excessively tight lateral retinaculum, possible quadriceps atrophy from an inhibitory mechanism, and also an antalgic gait to the symptomatic side.

Imaging

While basic information can be obtained with a normal 3-view study of the knee (anteroposterior [AP], lateral, and merchant view), the most information can be obtained from a weight-bearing Rosenberg view (45-degree flexion posterior–anterior view) as well as weight-bearing both limb full-length alignment films. These two weight-bearing films help to not only quantify the amount of joint space narrowing and relative chondral involvement to include potential subchondral sclerosis or collapse but also the weight-bearing axis of the affected limb in question. Computed tomography (CT) scans can also be helpful but of limited utility for everyday use. CT scans, to include CT arthrograms, can be useful in the setting of evaluating subchondral and osseous lesions, displaced osteochondral segments, assessments of the sequelae of prior surgical cartilage restoration procedures performed, and for patients unable to obtain magnetic resonance imaging (MRI) secondary to medically related contraindications. MRI is truly the workhorse of not only the in-office evaluations of articular cartilage but also in the research setting. The improvement in many cartilage-specific imaging protocols has dramatically improved the visualization and quantification of chondral and osteochondral lesions. T1-rho imaging, from a research perspective, is quite useful as an indirect way of evaluating the water content and glycosaminoglycan (GAG) content of articular cartilage, as well as its ability to review other biochemical markers for chondral health. While stronger MRI magnets have become more prevalent and can provide better resolution, it is the desired image sequences that are of importance when reviewing the cartilage as well as the remaining knee structures, such as meniscus, ligaments, tendons, and even bone. While there are many radiographic-based scoring systems to assess the structural outcomes from cartilage restoration procedures, still none of these to date correlate with the clinical outcomes of these procedures. CT and MRI scans, combined, can also provide valuable information for defining patellofemoral pathology as it pertains to chondral-based lesions and the potential for underlying maltracking. Both the tibial tubercle trochlear groove (TTTG) and the tibial tubercle posterior cruciate ligament (TT-PCL) measurements can be obtained on each. More often, the TTTG is used. The normal range for the TTTG is less than 15 mm, whereas an elevated distance is defined as greater than 20 mm. CT-based measurements have been shown to be more reproducibly accurate than MRI-based assessments, with the latter resulting in discrepancies in measurements by up to 4 mm. These measurements can be helpful in guiding treatment measures should specific patellar facet chondral lesions exist in the setting of an elevated TTTG.

Decision-Making Principles

Indications for Cartilage Restoration

Presuming there is no gross block to range of motion (ROM) or loose osteochondral fragment from either an acute injury or from chronic repetitive trauma, conservative care is the mainstay for initial treatment of articular lesions and defects. Physical therapy, to include activity modification and pain modalities, and adjuncts are important, but also a global picture of body habitus and weight reduction is vital if applicable. Injection therapy has shown equivocal results in the literature. While the heterogeneity of viscosupplementation molecular weights and processing as well as the stage of arthritis reported in the literature adds to these equivocal results, a recent systematic review reported a positive benefit for younger patients with early chondromalacia treated with intra-articular hyaluronic acid injection therapy. Surgical treatment is indicated in grade III or IV full-thickness chondral lesions after conservative nonoperative treatment measures have failed to provide adequate symptom relief. At this point, not only is it important to discuss with the patient what their expectations are moving forward, but also the expectations of what the surgical procedure can yield in terms of outcomes and longevity of symptom relief.

Contraindications

Inflammatory arthropathies, tricompartmental arthrosis, coronal malalignment, meniscal deficiency, collateral or cruciate ligament laxity, smoking, and obesity (BMI >35) are all considered contraindications to cartilage restorative procedures unless corrected prior to or during the surgery, if applicable. While tricompartmental arthrosis is considered a strict contraindication, in young patients with intolerable symptoms and no other available treatment options cartilage restoration procedures can still be considered.

Treatment Algorithm

There are multiple factors that interplay to determine what cartilage restoration procedure would be best served to address the patient-specific symptomatic complaints at hand. Having said that, the lesion location and size are the two main considerations when determining a treatment strategy. More commonly, the medial femoral condyle and the patellofemoral joint are the main locations where focal chondral lesions occur. Given the tibiofemoral and patellofemoral compartments see drastically different forces directed throughout their arc of motion, compression versus shear respectively, different surgical treatment modalities should be considered for each.

Osteochondritis Dissecans Lesions

Treatment decisions in osteochondritis dissecans (OCD) lesions are based on the presence of open growth plates, size, stability, and displacement of the fragment. Stable OCD lesions in juvenile patients with an open physis should be treated nonoperatively because these lesions have a greater tendency toward resolution and healing. However, if the fragment is displaced, every attempt should be made to reduce and fix the unstable fragment in patients with either open or closed physis. Headless compression screws and bioabsorbable pins can be used for fixation with satisfactory union rates. In some cases, fragments are not amenable to fixation due to comminution or inadequate subchondral component of the fragment. Removal of unstable fragments as a sole procedure is reserved for patients with low functional demands or those who are unable to follow rehabilitation protocols after repair. In long-term follow-up studies radiographic evidence of early degenerative joint disease was found in 65% to 71% of patients who underwent excision of OCD without any cartilage repair techniques. A recently published randomized trial has compared the outcomes of osteochondral allograft transplantation (OAT) and microfracture procedures for the treatment of OCD in young active athletes at an average of 10 years follow-up. The OAT technique allowed for a higher rate of return to and maintenance of sports (75%) at the preinjury level compared with microfracture (37%). Another multicenter study revealed functional improvement and pain relief in 85% of patients after ACI despite the complexity and severity of the osteochondral lesions. Fresh OAT is another option for treatment for OCD lesions of the femoral condyle with 70% good or excellent results.

Patient Age and Defect Chronicity

The age-dependent outcomes of marrow stimulation techniques are still continuing to be reported today. Cell numbers and their metabolic activity decline over time resulting in poor healing response in older patients. As a result, the clinical success rate of microfracture has been most consistent in patients under the age of 40 years. However, failure rates of other cartilage restoration techniques in older patients, such as ACI, OATs, and osteochondral allografting, are comparable with rates reported in younger patient groups. Depth of injury is also found to be age-related. Adolescents tend to develop osteochondral lesions, whereas adults have a tendency to get pure chondral lesions, possibly because of the well-developed and matured calcified zone. Time since onset of symptoms is an essential variable that should be taken into account because delayed treatment tends to result in less-predictable outcomes whereas significant improvements in the clinical scores were more frequent with a preoperative duration of symptoms of less than 12 months.

Treatment Options

Before planning a treatment procedure, patient-specific and lesion-specific variables must be taken into consideration. Physical condition and readiness of the patient for an extended rehabilitation program, concomitant knee pathologies, and limb alignment hold the key for success or failure in cartilage repair. There are several techniques described for the management of cartilage lesions. Examples of current attempts at cartilage restoration include marrow stimulating techniques, osteochondral autografts, autologous chondrocyte transplantation, particulated juvenile cartilage allograft, and OAT. Débridement and lavage is one of the most basic options and indicated for low-demand older patients with small lesions. Although symptomatic relief from this technique is not likely predictable, arthroscopic débridement can reduce pain in more than half of the patients; however, this benefit generally diminishes after 1 year. Additionally, unstable chondral flaps and loose bodies that cause mechanical symptoms can be removed with a very short recovery time and can be repeated if needed. Currently this technique is reserved for small lesions found incidentally during arthroscopy or low-demand patients who could not adjust to activity or weight-bearing restrictions postoperatively.

Marrow Stimulation

Biological rationale behind marrow stimulation techniques is that direct stimulation of mesenchymal stem cells (MSCs) in the subchondral bone could direct these cells to the chondrogenic pathway to initiate a healing response. Marrow stimulating techniques have been used to treat cartilage defects since 1959 when Pridie introduced subchondral drilling with K-wires. Later Johnson described the abrasion of sclerotic lesion with a burr to expose vascularity, providing a tissue bed for blood clot attachment. Finally Steadman introduced the microfracture technique to avoid heat necrosis from drilling. In his technique, the bone plate is not completely destroyed in comparison to an abrasion chondroplasty. Microfracture involves débridement of loose and unstable cartilage back to a stable rim. Then specially designed awls are used to make multiple perforations, or microfractures, into the subchondral bone plate. Perforation of subchondral bone results in the influx of marrow elements with the formation of blood clot in the defect. It is important to create a well-contained lesion because rims will support the fibrin clot within lesion. As noted it is crucial to breach the calcified cartilage layer to gain better access to the bone marrow stroma. This calcified layer appears to be at least 6 mm beneath the surface of the articular cartilage. Thus a routine awl will not be sufficient to breach this calcified layer in most knees, and it has been suggested that nanofracture technique will allow for deeper drilling to overcome this obstacle. Histologic findings showed that drilling to a depth of 6 mm had superior results in an animal model compared with drilling to 2 mm, without a deleterious effect on the subchondral bone. Over time this blood clot is slowly remodeled into primarily fibrocartilage rather than normal hyaline articular cartilage. Mature fibrocartilage is predominantly type I collagen with minimal amounts of type II collagen, resulting in a less-durable construct with inferior wear characteristics. The advantages of marrow stimulation techniques include their minimal invasive nature with low technical demands and favorable cost-effectiveness ratio. On the other hand, they require a prolonged restricted weight-bearing period of 4 to 6 weeks and use of a continuous passive motion (CPM) device for 6 to 8 hours per day, for 6 weeks.

Osteochondral Autograft Transfer

Osteochondral autograft transfer technique involves transfer of one or more cylindrical osteochondral plugs into the cartilage defect. The lesions should be small to medium-sized (0.5 to 4 cm 2 ) because the amount of donor tissue available is limited. Single or multiple small osteochondral plugs can be harvested to match the lesion's diameter. Traditionally plugs are harvested from less-weight-bearing areas of articular surface, such as the periphery of the trochlea and the intercondylar notch. The lesion is prepared with a punch to create a recipient socket that matches the plugs. Both preparing the socket and harvesting plugs require tubular cutting instruments such as OATS (Arthrex, Naples, FL), mosaicplasty (Smith and Nephew, Andover, MA), or COR (Depuy Mitek, Raynham, MA) to place plugs orthogonal to the articular surface to avoid graft obliquity. Multiple plugs can be used to fill larger defects, but it could be difficult to match the contour of the defective articular surface to the donor plug. Elevated angled grafts relative to articular surface result in elevated contact pressures, so it is suggested to leave an edge slightly sunk rather than elevated. Thus ideal locations for osteochondral autograft transfer are the convex surfaces of the femoral condyles rather than the patellofemoral joint and tibia with their varying surfaces, which make plugs more difficult to fit in place. It is crucial to place grafts in a press-fit fashion for maintaining stability until osseous integration of the plug and socket occurs. This procedure offers several advantages over microfracture or chondrocyte implantation techniques, including the ability to perform the procedure in a single-stage operation, transplanting an autogenous living hyaline cartilage, decreased cost, and relatively brief rehabilitation period. Major limitations of this procedure include donor site morbidity and the limited availability of grafts. Residual gaps between plugs may affect the quality of healing and there is an inherent risk for cartilage or bone collapse. The postoperative recovery requires a short period of non-weight bearing and the use of a CPM for up to 6 weeks.

Autologous Chondrocyte Implantation

The rationale behind ACI is to cover the cartilage defect with autologous chondrocytes, which have been cultured in vitro. This technique was first described by Brittberg et al. in 1994 and is one of the first tissue engineering techniques for articular cartilage regeneration. ACI is currently a two-stage procedure. First a cartilage biopsy (weight 200 to 300 mg) is taken from a non-weight-bearing area of the affected joint and transferred to a laboratory. The chondrocytes are isolated from the cartilage tissue by enzymatic digestion and then expanded in monolayer culture. The optimal density of the cells during reimplantation remains debated. Generally, a final concentration of 2 to 3 × 10 7 chondrocytes/mL is recommended for medium-sized defects, but the number of available cells is limited by the amount of cartilage that can be collected. This expansion amplifies the total number of cells for implantation, allowing the surgeon to fill the cartilage defect. The cell suspension is returned to the defect during the second stage of the procedure and held in place with a periosteal patch or membrane. ACI can be performed for high-demand patients who have failed arthroscopic débridement or microfracture. The technique is indicated for larger (2 to 10 cm 2 ) symptomatic lesions involving the femoral condyles, trochlea, and the patella. The primary theoretical advantage of ACI is to provide hyaline-like cartilage rather than fibrocartilage, resulting in better long-term outcomes and durability of healing tissue. Clinical results are encouraging and overall the patients are satisfied. This technique is however not without its limitations. These include technical complexity and cost of the two surgical procedures, de-differentiation of chondrocytes during in vitro expansion and periosteal graft delamination, and late periosteal hypertrophy. Also, previous marrow stimulation techniques have a strong negative effect on outcomes of subsequent cartilage repair with ACI, limiting its use as a salvage procedure. Second-generation ACI procedures involve use of collagen sheets to replace periosteal flaps. These collagen matrices avoid graft harvesting and donor site morbidity and using cell-free collagen sheets dramatically eliminated adverse events related to graft hypertrophy and delamination. In the third generation of ACI the cultured chondrocyte cells are seeded directly onto a biodegradable porcine type I/III collagen scaffold. Matrix Autologous Chondrocyte Implantation ([MACI] Genzyme, CA) method has been in clinical use for a number of years in Europe and is now approved by the Food and Drug Administration (FDA) and available in the United States. This enables three-dimensional (3D) culture of chondrocytes, aiming to prevent de-differentiation and loss of phenotype. Uneven distribution of chondrocytes within the defect and the potential for cell leakage from the defects that often lack intact cartilage rims can be prevented through using scaffolds. Additionally, the scaffolds used may act as a barrier to fibroblast invasion. Outcomes of these techniques have been promising and are at least equivalent to those achieved with ACI, with reported good clinical medium-term results. The postoperative treatment is broadly similar to marrow stimulation techniques while time periods are generally extended. Rehabilitation should focus on maintaining muscle function and joint flexibility, with the use of CPM. Full weight bearing is avoided for 8 to 12 weeks.

Particulated Juvenile Cartilage Allograft

In the past, allograft transplants were limited to osteochondral grafts because it has been generally accepted that graft incorporation to host tissue was only possible at the bone level. The concept that cartilage could be transplanted without its underlying bony component is a fairly new and innovative approach. Particulated juvenile cartilage allograft technique DeNovo NT (Zimmer, Warsaw, IN) uses human juvenile allograft articular cartilage minced into small pieces. Mechanical mincing of cartilage into 1- to 2-mm pieces was crucial for successful cartilage repair. This promotes chondrocytes escaping from the extracellular matrix (ECM), multiplying and migrating to surrounding tissues to form a new hyaline-like cartilage tissue matrix that integrates with the surrounding host tissue. Cartilage is retrieved from the femoral condyle of donors aged 0 to 13 years. Because juvenile chondrocytes are capable of producing greater amounts of ECM compared with mature chondrocytes, these cells also do not stimulate an immunogenic response in vivo. DeNovo NT has an average 40-day shelf life similar to a fresh osteochondral allograft. During surgery, fragments are mixed with fibrin glue to make a putty-like structure to fill the osteochondral defect so that no sewing of a patch is needed. Each package contains 30 to 200 particles and fills defects up to 2.5 cm 2 , so multiple packets can be used for larger lesions. The use of DeNovo NT has the advantage of being a single-stage procedure and offers unlimited graft material for large lesions. At postoperative period patients are limited in weight-bearing for 2 weeks for small lesions, and 6 weeks for larger lesions. Although the preliminary clinical reports show encouraging results, clinical data are still limited.

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