Preserving the Articulating Surface of the Knee

Introduction

Hyaline articular cartilage plays an integral role in the function of the knee joint. Isolated chondral lesions are incompletely understood, but once damaged, there is very little capacity for spontaneous healing due to intrinsically poor blood supply ( Fig. 9.1 ). Thus, the risk of patient pain, effusions, mechanical symptoms, decreased activity and quality of life, and the possibility of progression to diffuse osteoarthritis (OA) remain a concern. Between 30,000 and 100,000 chondral procedures are performed annually in the United States, and an annual incidence growth of 5% has been reported. The lesions are most commonly found in the medial compartment, followed by the patellofemoral compartment, and have been theorized to occur in approximately 12% of the population.

Numerous surgical interventions have been developed and refined over the last few decades in an attempt to preserve the articular surface of the knee. Conservative treatment options have more recently focused attention on injectable biologics in an effort to stimulate the body’s natural resources and create an intraarticular milieu suitable for healing. Reparative marrow-stimulation techniques–most notably microfracture–can be used at the site of a chondral defect in an attempt to induce fibrocartilage repair tissue formation after penetration of the subchondral bone. Restorative cartilage procedures (mosaicplasty, osteochondral allograft/autograft, particulated juvenile cartilage graft, autologous chondrocyte implantation [ACI]), by contrast, replace the native defect site with host or donor articular hyaline cartilage. These latter options have garnered more attention in the last decade as advanced efforts to provide pain relief, alter arthritic progression patterns, and hopefully delay or avoid arthroplasty.

Generally, varying specifications for use exists for each of the aforementioned procedures. However, no unified consensus exists on which cartilage repair or restoration technique exhibits the most successful long-term clinical outcomes. This chapter focuses on the basic science of cartilage structure, discusses the aforementioned surgical and nonsurgical preservation techniques for the articular cartilage of the knee joint, and highlights expected future directions of study in the topic of surface cartilage defect treatment.

Basics of Cartilage Structure

Cartilage is present in various parts of the human body and it is categorized into three different types: fibrocartilage, elastic cartilage, and hyaline cartilage. Each type has a unique function, structure, and composition. Hyaline cartilage, also known as articular cartilage, covers the articular surfaces between bones to provide a load-supporting, low-friction interface. This type of cartilage has low cell density and low proliferative activity and is avascular in nature, which makes innate regeneration nearly impossible.

Hyaline cartilage is primarily composed of water, chondrocytes, and an extracellular matrix (ECM). Chondrocytes are the cellular component of this type of cartilage and are highly differentiated cells with low proliferative activity. They are found in low abundance–only 1%–5% of cartilage by volume–but have high metabolic activity because they are responsible for maintaining homeostasis within the elaborate ECM. Mature chondrocytes lack cell–cell interactions and are instead surrounded by a pericellular matrix that extends radially from the cell surface. Chondrocyte function is affected by the surrounding environment including factors such as the compressive load within a joint, a phenomenon referred to as mechanotransduction. The ECM is composed of water and molecules including collagen, proteoglycans, and superficial zone protein. Water is the largest component of articular cartilage, responsible for 70%–80% by weight, and interacts with the extracellular components through its polar molecular structure to provide unique biomechanical properties.

There are more than 28 types of collagen identified within the human body. Type II collagen is the most prevalent type within hyaline cartilage and comprises approximately 50% of its dry weight. It is also a major component of the ECM. All types of collagen share a central core composed mostly of glycine, proline, and hydroxyproline causing the formation of a left-handed helix. These individual helices further assemble into right-handed triple helix microfibrils that form larger fibrils through end-to-end fusion and lateral bundling. These collagen fibrils are then arranged in different orientations in relation to the articular surface depending on their depth within the hyaline cartilage structure, and they provide stiffness to the tissue allowing it to bear weight.

The articular cartilage ECM also contains other molecules, the most prevalent of which are proteoglycans consisting of a protein core and many polysaccharides (primarily glycosaminoglycans [GAGs]) extending perpendicularly. GAGs are linear polysaccharides composed of repeating disaccharide units. The most common GAGs in hyaline cartilage are hyaluronan, dermatan sulfate, keratan sulfate, chondroitin 6-sulfate, and chondroitin 4-sulfate. Hyaluronan is unique in that it is the largest GAG, does not carry a negative charge, and is able to bind strongly with aggrecan–the main proteoglycan found in articular cartilage. The strong binding between hyaluronan and aggrecan results in the formation of large proteoglycan aggregates, and a fixed negative charge within the ECM causes a significant osmotic pressure in the cartilage’s interaction with synovial fluid. The end result is significant accumulation of fluid and swelling, known as the Donnan effect, that works with the collagen structure to produce the weight-bearing capability of articular cartilage.

Synovial fluid directly plays an important role in maintaining the articular cartilage. Synovial fluid is composed of protein-rich plasma ultrafiltrate and hyaluronan. As cartilage is avascular, the synovial fluid is responsible for providing nutrients through simple diffusion and compression–relaxation cycles during weight-bearing. It also contains a protein called “superficial zone protein”—or lubricin—which is also present on the surface of hyaline cartilage and contributes to the lubrication and ease of joint movement. Additionally, synovial fluid contributes to the load-bearing capacity by increasing its viscosity in response to pressure.

Articular cartilage is divided based on depth and composition into four structural zones: the superficial zone, the middle or transitional zone, the deep or radial zone, and the calcified zone. The outermost layer of cartilage is covered by the lamina splendens , which is a layer of proteins thought to be produced by the accumulation of proteins from synovial fluid that acts as a protective, low-friction layer for the cartilage. Immediately deep to that is the superficial layer of cartilage, which is densely packed with collagen fibers oriented parallel to the articulating surface and with a low concentration of proteoglycans. Chondrocytes in the superficial layer are flat in shape and also oriented parallel to the articulating surface. They produce proteins to lubricate the articular surface such as lubricin, which are not present in deeper zones. The middle zone is responsible for 40%–60% of cartilage thickness and has the highest concentration of proteoglycans. It has low cellular density, and its most prevalent ECM component is type II collagen arranged in arches. The chondrocytes here are round and produce a large amount of type II collagen and proteoglycans, specifically aggrecan. The deep zone has a lower cell density than the superficial or middle zones and contains type II collagen fibers oriented perpendicular to both the subchondral bone and articular surface. The chondrocytes in the deep zone appear elongated and are oriented parallel to the collagen fibers. Finally, the calcified zone contains hydroxyapatite and acts as a transitional zone between the cartilage and subchondral bone.

Injury to the articular surface can occur secondary to trauma of the joint causing disruption of the cartilage and formation of a focal chondral defect. The deeper cartilage layers, or possibly the subchondral bone, become exposed leading to pain, stiffness, and loss of function. If left untreated, focal chondral defects can progress to OA over time due to further degeneration of the surrounding cartilage. OA is caused by a combination of degenerative and abnormal remodeling processes within the cartilage in response to repetitive stress. Cartilage has low proliferative capacity making these processes nearly irreversible. Changes in the ECM begin in the superficial zone with the appearance of erosions, fissures, and fibrillation. The disruption of the collagen network results in a loss of proteoglycans that eventually inhibits its biomechanical function. The innate type II cartilage shows decreased fiber diameter while the type I cartilage concentration increases, representing the formation of fibrocartilage. Fragmentation continues until the subchondral bone becomes exposed, which allows direct force to be applied to the bone causing remodeling and thickening. Chondrocytes also undergo a series of changes during the development of OA including proliferation and pericellular matrix remodeling. Eventually, the chondrocytes die and release necrosis factors that induce apoptosis of surrounding chondrocytes. This leads to further degradation of the cartilage structure and eventual exposure of the subchondral bone.

Orthobiologic Injections

Platelet-Rich Plasma

Platelet-rich plasma (PRP) is plasma containing supraphysiologic levels of platelets and platelet-derived growth factors used as a therapeutic modality for treatment of symptomatic cartilage defects and OA. PRP is produced from a patient’s venous blood that has been centrifuged to isolate the platelets, plasma, and growth factors ( Fig. 9.2 ). Platelets produce α granules, which contain many growth factors including transforming growth factor-β (TGF-β), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF). These growth factors have been found to be involved in tissue repair, and the goal is that PRP injections in theory could contribute to cartilage regeneration.

Recent in vitro and in vivo studies have shown that PRP functions by inducing cartilage regeneration and decreasing inflammation. Chondrocytes treated in vitro with PRP have shown increased proliferation and increased synthesis of type II collagen and GAGs. Additionally, in vitro studies have shown that PRP inhibits nuclear factor-κB (NF-κB), which is a transcription factor for the expression of proinflammatory and catabolic cytokines IL-1β and TNFα. In vivo, synovial fluid samples aspirated at 12 and 24 months after PRP injections trended toward decreased levels of IL-1β and TNFα, although the difference compared with treatment with HA was not statistically significant.

The existing literature varies in terms of PRP preparation technique, platelet concentration, white blood cell concentration, amount injected into the joint, and presence of an activating agent such as calcium chloride. The therapeutic range for platelet concentration is thought to be between two and six times higher than physiologic levels. A recent systematic review of six level I studies found significant improvement in clinical outcomes and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores on OA patients treated with PRP when compared with HA at 3–12 months after injection. Very few studies have investigated outcomes past 1 year, but the available data suggest a decline in outcomes between 1 and 2 years after injection. The nuances of ideal PRP preparation to help maximize efficacy have begun to be elucidated in recent years, however. A systematic review of nine level I and level II studies that differentiated between leukocyte-rich and leukocyte-poor PRP found significant improvement in OA patients treated with leukocyte-poor PRP compared with HA or placebo but not with leukocyte-rich PRP. These data support the need for standardization of PRP preparations in order to maximize efficacy in all patients.