Articular Cartilage of the Knee: Defects, Degeneration, and Preservation
Cassandra A. Lee, MD, FAAOS
Dr. Lee or an immediate family member is a member of a speakers’ bureau or has made paid presentations on behalf of Genzyme and Smith & Nephew and serves as a board member, owner, officer, or committee member of the American Academy of Orthopaedic Surgeons, the American Orthopaedic Society for Sports Medicine, and the Arthroscopy Association of North America.
ABSTRACT
Knee articular cartilage defects are commonly found incidentally with a frequency of occurrence correlating to the age of the patient. Articular cartilage tissue is highly organized with specific biomechanical properties that make it difficult to re-create. Because it is aneural and avascular, the innate healing potential is limited. Symptomatic chondral defects present a clinical challenge to manage, especially among athletes and other active patients. Defects are associated with pain and functional impairment that may progress toward joint degeneration and frank osteoarthritis. When nonsurgical methodologies fail to improve symptoms, surgical intervention can facilitate intrinsic repair or use external factors to regenerate a functional tissue that allows for return to activity.
Keywords: articular cartilage; cartilage regeneration; joint preservation; orthobiologic agents
Introduction
Focal articular cartilage defects are common, often incidental findings occurring in up to two-thirds of patients undergoing knee arthroscopy.1 When symptomatic cartilage lesions can cause disability that is on the spectrum of knee osteoarthritis, with symptoms ranging from pain and swelling to mechanical symptoms such as locking and catching to functional impairment. Osteoarthritis is irreversible and affects up to 35% of patients between 50 and 59 years of age and increases to more than 55% in individuals older than 70 years. It has been known since the Roman era that cartilage is subject to injury, and it has been observed that partial-thickness articular cartilage injuries cannot be repaired.2 Articular cartilage lesions result from idiopathic, repetitive microtrauma, or overt traumatic events. They are highly associated with injuries such as anterior cruciate ligament tears,3 meniscus tears, patellar dislocation,4 and malalignment. Lesions may appear to affect only the overlying cartilage, but there is potential to affect the underlying subchondral bone. Therefore, careful attention should be paid to the osteochondral unit as a whole. The natural history of cartilage defects is not completely understood. Once the osteochondral unit is damaged, altered joint contact forces may occur on adjacent chondral surfaces and subchondral bone, leading to a vicious cycle of propagating an inflammatory response with release of cartilage degradative enzymes and further joint degradation, eventually leading to and progressing toward osteoarthritis. Surgical interventions are performed to decrease symptoms, improve function, and alter the course and delay the progression of joint degeneration. Understanding the connective tissue’s unique biomechanical properties helps to dictate rationale for treatment. Evaluation, diagnosis, and management of injuries are discussed.
Microanatomy
Articular cartilage is a highly organized connective tissue with complex biomechanical properties with substantial durability whose purpose is to decrease forces through the joints.5 The half-life of type II collagen is estimated to be approximately 117 years, which limits regenerative potential. Mature chondrocytes are embedded in a structural framework of collagen and matrix, possessing low anabolic and proliferative activities because of limited vascular, nerve, and lymphatic supply. Nutrients to the chondrocytes are delivered by interstitial fluid in a complex interplay between the intact dense matrix and fluid flow, which contribute to the biomechanical properties of cartilage as a viscoelastic tissue. The healing potential for cartilage defects is limited, and therefore spontaneous healing does not occur. Partial-thickness tears do not heal, whereas full-thickness osteochondral defects can fill to some degree
with fibrocartilage scar tissue. The fibrous repair tissue made up of type I collagen has decreased stiffness with poor wear characteristics compared with native tissue, often tending toward advancing degeneration and eventually osteoarthritis.
with fibrocartilage scar tissue. The fibrous repair tissue made up of type I collagen has decreased stiffness with poor wear characteristics compared with native tissue, often tending toward advancing degeneration and eventually osteoarthritis.
Management of isolated chondral or osteochondral defects of the knee can be difficult in young patients because activity, functional demands, and expectations do not align with viability or longevity of surgical treatments such as partial or total knee arthroplasty.
Diagnosis
It is challenging to ascertain whether to manage articular cartilage defects that are found incidentally on advanced imaging or on diagnostic arthroscopy. Determining if an articular cartilage lesion is symptomatic may be even more difficult to ascertain when patients have additional knee pathologies such as meniscus insufficiency, malalignment, or ligamentous instability. Articular cartilage defects do not have a specific finding on physical examination but patients often present with pain and swelling. In an isolated defect, an effusion may be present with preserved knee motion. Patients may complain of possible locking of the knee if there are displaced osteochondral fragments. In larger or bipolar defects, more mechanical symptoms are present, such as catching or clicking with knee motion. Examination to assess alignment and ligamentous stability is also necessary.
Obtaining a detailed history may shed light on a traumatic etiology such as a fall or twisting injury. Idiopathic or repetitive microtrauma may present with an insidious onset of pain and dysfunction.
Imaging
Weight-bearing radiographs such as AP views in full extension, PA views in 45° of flexion, lateral and patellofemoral views, and full-length hip-to-ankle AP views are essential to assess joint degenerative changes, joint-space narrowing, and limb alignment. Size markers are also necessary if sizing radiographs are obtained to account for image magnification.
MRI is an effective tool in identifying cartilage lesions, with 3T MRI showing greater diagnostic accuracy than 1.5T MRI. As discussed in a 2020 study, cartilage-specific imaging protocols have improved the quality of imaging, allowing for accurate assessment of lesions preoperatively and monitoring cartilage after repair procedures.6 Intermediate-weighted images (T1-weighted, T2-weighted, and proton-density-weighted) are most widely used for visualizing chondral lesions, with proton density images having the best results; images are directly correlated with the size and location of the defect according to a 2019 study. More recently, T2 mapping, T1 rho, and diffusion-weighted imaging have been used more for research rather than clinical use. Understanding the size of a lesion is helpful in determining treatment options and prognosis. MRI is also used to assess ligamentous and meniscal structures for injury.
CT evaluates the subchondral bone as part of the osteochondral unit. For the patellofemoral joint, the tibial tubercle-to-trochlear groove distance is measured to determine the need for unloading with an anteromedialization/medialization osteotomy. In focal, distal, and lateral patellar lesions or medial, central, and/or panpatellar cartilage pathology, an anteromedialization tibial tubercle osteotomy is recommended. In cases of patellar instability where the tibial tubercle is lateralized (tibial tubercle-to-trochlear groove distance, >15 mm), medialization with a soft-tissue stabilization procedure is recommended. When considering surgical management of chondral defects of the patellofemoral joint, addition of a tibial tubercle osteotomy results in good to excellent patient-reported outcomes (PROs) directly correlating with the size and location of defect, according to a 2019 study.7 CT arthrography can be used to assess the stability of an osteochondritis dissecans lesion/fragment in cases where MRI is not possible.
Nonsurgical Treatment Options
After an articular defect is determined to be symptomatic, nonsurgical treatment begins with relative rest, activity modification, and physical therapy for 3 to 6 months, focusing on strengthening and stabilization. Oral anti-inflammatory medications, nutraceutical agents (glucosamine, chondroitin sulfate), and bracing treatment can also be used. An unloader brace can be effective in cases with unilateral compartment overload due to either malalignment or meniscus deficiency. Injectable therapies such as steroids and/or viscosupplementation or orthobiologic agents can be explored to decrease the inflammatory response and improve symptoms. Orthobiologic agents include platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) in the form of bone marrow aspirate concentrate (BMAC) or stromal vascular fraction (SVF). Many of these agents demonstrate promising early results, but high-level randomized controlled trials are warranted to determine if these agents are truly effective. If these measures fail to provide acceptable pain relief, surgery may be indicated.
Orthobiologic Agents
Viscosupplementation is a procedure that uses hyaluronic acid, which is a natural glycosaminoglycan that lubricates and provides some shock absorption via
action as an osmotic buffer in joints. Meta-analyses of viscosupplementation for the management of osteoarthritis have found statistically significant improvements in PROs of pain, function, and stiffness, but none of these improvements met the minimal clinically important improvement thresholds.8,9
action as an osmotic buffer in joints. Meta-analyses of viscosupplementation for the management of osteoarthritis have found statistically significant improvements in PROs of pain, function, and stiffness, but none of these improvements met the minimal clinically important improvement thresholds.8,9
PRP is an autologous plasma product that is a well-proven treatment for osteoarthritis of the knee.10 Once centrifuged and processed, it contains approximately four to five times more platelets than unprocessed blood while also containing thousands of proteins including growth factors. It is the potential of these growth factors and inflammatory mediators released by the platelets in PRP that makes it so appealing for musculoskeletal applications. However, because of the varied preparations for the production of PRP, no standardization of product exists. Current evidence suggests that direct injection of PRP into the joint can control the inflammatory environment by preventing activation of nuclear factor kappa B,11 which inhibits synthesis of anabolic-related genes such as type II collagen. PRP also exerts a potent anti-inflammatory effect because of concentrated levels of interleukin-1 receptor antagonist12 as well as other growth factor components that help stimulate growth of autologous chondrocytes and MSCs and components of the extracellular matrix via synthesis of proteoglycans and collagen.13 Many studies have reported positive effects of PRP on patients with osteoarthritis, including patients who underwent arthroscopic débridement and microfracture.14 In trials comparing PRP versus hyaluronic acid for the management of osteoarthritis, PRP had longer and better effectiveness in reducing pain and improving function.15 Overall, PRP has shown a tendency toward better efficacy in management of the early stages of osteoarthritis as well as positive effects in the management of all stages of osteoarthritis.16
MSCs and growth factors can be derived from BMAC. It has a higher concentration of chondrogenic cells, MSCs, and growth factors in comparison to bone marrow itself that are theorized to improve the healing response by decreasing apoptosis and inflammation and activate cell proliferation and differentiation. The mechanism by which BMAC affects osteoarthritis is unknown. In a prospective placebo-controlled pilot study comparing BMAC with saline in patients with bilateral knee osteoarthritis, no significant difference in pain relief and function occurred between both sides.17 Injection of BMAC with expanded MSCs is currently in phase I/II clinical trials, and has been shown to have increased clinical and functional efficacy compared with hyaluronic acid, with no adverse effects in the long term (4 years follow-up).18 Studies on BMAC effects on focal full-thickness cartilage defects have reported more favorable outcomes when combined with microfracture19 or embedded within a hyaluronic acid-based scaffold.20
MSCs have demonstrated chondrogenic potential but require special laboratory conditions and weeks for cell expansion. Adipocyte MSCs secrete anti-inflammatory soluble factors that can stop cartilage destruction and degradation but also possess regenerative capacities. They can be derived from an abundant supply that is easy to harvest with a minimally invasive liposuction procedure. The lipoaspirate is mechanically or enzymatically processed. The resultant SVF does not require tissue culture and expansion; it contains a heterogeneous mixture of stem, progenitor, and adult cells but not adipocytes and has a very low concentration of leukocytes.21 Adipocyte MSCs in SVF secrete soluble factors with anti-inflammatory, immunomodulatory, and analgesic effects. SVF is often suspended in PRP for delivery, with multiple case series showing improved joint function and decreased pain scores with limited evidence of improved cartilage thickness.22 A 2020 randomized controlled trial has supported the use of SVF in the management of knee osteoarthritis, significantly improving symptoms for 12 months.23
Despite promising results in midterm relief of symptoms and improvement of function, orthobiologics have yet to be consistently shown to regenerate articular cartilage.18 Surgical intervention may provide the best long-term success for regenerating tissue, but patient expectations should be realistic with regard to having to undergo extensive rehabilitation and limitation of activity for an extended period of time during the healing and regenerative period.
Surgical Treatment Options
Surgical treatment should focus on removing the underlying cause of inflammation and restoration of the osteochondral unit. The best choice for a surgical procedure depends on lesion size, depth, and location, with no clear algorithm existing for surgical decision making. Traditionally, lesions considered treatable in patients younger than 40 years are full-thickness lesions (Outerbridge grade III to IV, or International Cartilage Repair Society grade 3 or 4; size, >2 cm2).24 Surgical strategies can be divided into palliative (eg, chondroplasty, débridement) versus reparative (eg, microfracture, drilling) versus restorative (eg, osteochondral autograft or allograft transfer, autologous chondrocyte implantation [ACI]). Long-term outcomes for these techniques are frequently debated. Realistic expectations are crucial to patient outcomes.
Débridement and Chondroplasty
Arthroscopic débridement is commonly performed as a first-line procedure. The goal of surgery is to reduce inflammatory mediators by débriding unstable chondral flaps and removing loose bodies within the joint, this may be ideal in patients with degenerative joint disease, high body mass index, or those who are in-season athletes. Because of the underlying chondral defect, symptomatic improvement is often temporary.
Marrow Stimulation and Microfracture
Reparative procedures that penetrate the subchondral bone plate to fill the cartilage defect with marrow elements and stimulate fibrocartilaginous repair is known as marrow stimulation (Figures 1 and 2). Initially described as open Kirschner wire drilling of the subchondral bone, marrow stimulation was refined from an open technique to the less invasive microfracture arthroscopic technique. Microfracture is considered the first-line treatment for chondral defects of the knee because it is minimally invasive with little surgical morbidity and low cost.25 It should be avoided when subchondral bone deficiency is present. The cartilage defect is identified under arthroscopic visualization. The edges of the lesion are débrided to stable, vertical borders of healthy cartilage with either an arthroscopic shaver or curet. The subchondral plate is then penetrated with perpendicular holes 2 to 3 mm apart. Cells, including MSCs, from the bone marrow fill the defect and mature into a fibrocartilage clot with irregular type I collagen deposition that has less capacity to resist shear forces when compared with native cartilage.26 Postoperatively, rehabilitation involves toe-touch weight bearing for 6 to 8 weeks with progression toward full weight bearing at 8 to 12 weeks. For patellofemoral lesions, patients can bear weight with the knee locked in full extension in the brace. Passive motion is introduced with the goal to return to full activity around 6 to 9 months postoperatively.
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