**1. Introduction**

Articular cartilage is a unique, biologically active tissue. In the knee, it serves as the endbearing surface for the distal femur and proximal tibia, forming a diarthrodial synovial joint capable of enduring years of impact loading. Made of hyaline cartilage, the near-frictionless surface distributes load throughout motion across 6 degrees of freedom, reducing stress transmission to the underlying subchondral bone. This permits weight-bearing during both activities of daily living and high-impact athletics. In fact, forces in the knee joint may approach 8-times body weight during deep knee bends(Reilly and Martens 1972) and pressures up to 12 MPa during maximal quadriceps contraction(Huberti and Hayes 1984) (a pressure equivalent to being ¾ mile under water). These biomechanical properties rely on compression and deformation, a direct result of the biphasic nature of articular cartilage consisting primarily of water and extracellular matrix. Variation in this tissue's thickness and the joint's radii of curvature further influence biomechanics because of compartmentalspecific loading profiles within the tibiofemoral and patellofemoral "joints" of the knee. Arthroscopic appearance of articular cartilage in the knee (Figure 1a) should display a glistening, smooth, white surface that is firm to manual or instrumented palpation. Any disruption in the smooth surface or the tactile feel is abnormal. The loss of articular cartilage is the *sine qua non* of osteoarthritis. Histologic examination reveals relatively hypocellular tissue that lacks a vascular supply, neural input and output, and lymphatic drainage. These features contribute to the minimal innate healing response of isolated chondral damage and also illustrate the difficulty in making a clinical diagnosis of an isolated chondral defect (Figure 1b). Further, the role of the subchondral bone and its complex interaction with the overlying layered structure of cartilage has been emphasized in recent literature, not only in defect creation and progression, but also in surgical treatments. At the current time, these surgical procedures, cartilage repair and restoration, are designed to prevent and/or delay the initiation and/or progression of osteoarthritis.

#### **2. Anatomy and biomechanics**

The knee joint is the largest in the human body. It is a modified hinge allowing motion in the flexion / extension (sagittal), varus / valgus (coronal), and internal / external rotation planes (axial). These motions have both osteocartilaginous and soft tissue ligamentous constraints. The patella articulates with the femoral trochlea and the medial and lateral femoral condyles articulate with the medial and lateral menisci and tibial plateaus. The

Management of Knee Articular Cartilage Injuries 105

femur – tibia geometrical asymmetry medially versus laterally plays a greater role. This is reflected by the nearly 300% increase in contact stress laterally versus 100% increase medially after total meniscectomy(Kettelkamp and Jacobs 1972; Fukubayashi and Kurosawa 1980). These findings clearly illustrate the chondroprotective role of the menisci in the knee

Fig. 2. The "ball-in-socket" schematic of the medial compartment articulation (left); the less congruent, convex-on-convex articulation of the lateral compartment (right) (reproduced with permission from Koo S, Rylander J, Andriacchi T: Knee joint kinematics during walking influences the spatial cartilage thickness distribution in the knee, in *Journal of* 

Fig. 3. 3a) Sagittal profile of knee with normal menisci. Axial load distributed across surfaces of menisci and articular cartilage; 3b) Sagittal profile of knee without meniscus. Axial load distributed over articular cartilage only. With same force and smaller area of articulation,

The patellofemoral articulation consists of the patella, the largest sesamoid in the human body, and the trochlea, a groove located on the anterior distal femur. The patella normally sits within a suprapatellar pouch in full extension and begins to engage the trochlea around 20 to 30 degrees of knee flexion. A vertically-oriented ridge on the articular surface of the patella separates the patella into medial and lateral facets. The superior 75% of the patella is articular cartilage, while the inferior 25% is non-articulating bone. The thickness of the articular cartilage in the patella can be the thickest in the human body, up to 5- or 6-mm (Scott 2005). This portends the ability to withstand high joint reactive forces seen in the patellofemoral articulation. The trochlea is separated into medial and lateral facets by a

Biomechanics 2011; 44(7): 1408. Publisher Elsevier).

increased stress transmitted to articular cartilage.

**2.2 Patellofemoral compartments** 

(Figures 3a, 3b).

collateral (medial and lateral collateral, MCL and LCL) and cruciate (anterior and posterior cruciate, ACL and PCL) ligaments are restraints to abnormal motion in one or more planes.

Fig. 1. 1a) Arthroscopic photograph of normal knee articular cartilage demonstrating smooth, white, glistening surface; 1b) Arthroscopic photograph of isolated, full-thickness chondral defect of femoral trochlea.

### **2.1 Tibiofemoral compartments**

Articular cartilage in the tibiofemoral joint articulates with both meniscus and opposing surface articular cartilage. The menisci increase surface contact area, thus reducing stress transmission to the under- or over-lying articular cartilage. Both anatomy and kinematics are significantly different within each of the tibiofemoral compartments(Iwaki, Pinskerova et al. 2000). This asymmetry is reflected in that the lateral compartment tends to axially rotate around a relatively stationary medial compartment with knee flexion.

Kinematically, the medial compartment of the knee operates like a ball (femoral condyle) and socket (tibial plateau and meniscus)(Scott 2005). In the sagittal plane, the medial femoral condyle is composed of two arcs of different radii of curvature and the medial tibial plateau of two angled flat surfaces(Iwaki, Pinskerova et al. 2000). The more anterior surface (extension radius / facet) of the femur has a larger radius than that of the posterior surface (flexion radius / facet). The tibia's angled flats, together with the firmly-attached medial meniscus, create a concavity in which the femoral condyles contact.

Contrary to the medial side, the lateral compartment of the knee has a convex-to-convex articulation in the sagittal plane (Figure 2). Without a lateral meniscus, the lateral compartment operates via nearly point-on-point contact. With a single radius of curvature, the femoral condyle tends to roll back on the tibial plateau, which supports a more looselyattached lateral meniscus, with knee flexion(Iwaki, Pinskerova et al. 2000). The fixed axis medially combined with greater mobility laterally supports the "screw-home mechanism" of tibial internal rotation with increasing knee flexion(Blankevoort, Huiskes et al. 1988).

Similar to the anatomic asymmetry between the medial and lateral compartments, the biomechanical loading profiles are also unique. In a normal knee, the lateral meniscus covers a greater surface area (~80%) of the plateau than the medial (~60%)(Clark and Ogden 1983), thus transmitting a larger proportion of the axial load while weight-bearing (50% medially versus 70% laterally)(Fukubayashi and Kurosawa 1980; Ahmed and Burke 1983). Following meniscectomy, all load is transmitted through the articular cartilage and the

collateral (medial and lateral collateral, MCL and LCL) and cruciate (anterior and posterior cruciate, ACL and PCL) ligaments are restraints to abnormal motion in one or more planes.

Fig. 1. 1a) Arthroscopic photograph of normal knee articular cartilage demonstrating smooth, white, glistening surface; 1b) Arthroscopic photograph of isolated, full-thickness

rotate around a relatively stationary medial compartment with knee flexion.

meniscus, create a concavity in which the femoral condyles contact.

Articular cartilage in the tibiofemoral joint articulates with both meniscus and opposing surface articular cartilage. The menisci increase surface contact area, thus reducing stress transmission to the under- or over-lying articular cartilage. Both anatomy and kinematics are significantly different within each of the tibiofemoral compartments(Iwaki, Pinskerova et al. 2000). This asymmetry is reflected in that the lateral compartment tends to axially

Kinematically, the medial compartment of the knee operates like a ball (femoral condyle) and socket (tibial plateau and meniscus)(Scott 2005). In the sagittal plane, the medial femoral condyle is composed of two arcs of different radii of curvature and the medial tibial plateau of two angled flat surfaces(Iwaki, Pinskerova et al. 2000). The more anterior surface (extension radius / facet) of the femur has a larger radius than that of the posterior surface (flexion radius / facet). The tibia's angled flats, together with the firmly-attached medial

Contrary to the medial side, the lateral compartment of the knee has a convex-to-convex articulation in the sagittal plane (Figure 2). Without a lateral meniscus, the lateral compartment operates via nearly point-on-point contact. With a single radius of curvature, the femoral condyle tends to roll back on the tibial plateau, which supports a more looselyattached lateral meniscus, with knee flexion(Iwaki, Pinskerova et al. 2000). The fixed axis medially combined with greater mobility laterally supports the "screw-home mechanism" of tibial internal rotation with increasing knee flexion(Blankevoort, Huiskes et al. 1988). Similar to the anatomic asymmetry between the medial and lateral compartments, the biomechanical loading profiles are also unique. In a normal knee, the lateral meniscus covers a greater surface area (~80%) of the plateau than the medial (~60%)(Clark and Ogden 1983), thus transmitting a larger proportion of the axial load while weight-bearing (50% medially versus 70% laterally)(Fukubayashi and Kurosawa 1980; Ahmed and Burke 1983). Following meniscectomy, all load is transmitted through the articular cartilage and the

chondral defect of femoral trochlea.

**2.1 Tibiofemoral compartments** 

femur – tibia geometrical asymmetry medially versus laterally plays a greater role. This is reflected by the nearly 300% increase in contact stress laterally versus 100% increase medially after total meniscectomy(Kettelkamp and Jacobs 1972; Fukubayashi and Kurosawa 1980). These findings clearly illustrate the chondroprotective role of the menisci in the knee (Figures 3a, 3b).

Fig. 2. The "ball-in-socket" schematic of the medial compartment articulation (left); the less congruent, convex-on-convex articulation of the lateral compartment (right) (reproduced with permission from Koo S, Rylander J, Andriacchi T: Knee joint kinematics during walking influences the spatial cartilage thickness distribution in the knee, in *Journal of*  Biomechanics 2011; 44(7): 1408. Publisher Elsevier).

Fig. 3. 3a) Sagittal profile of knee with normal menisci. Axial load distributed across surfaces of menisci and articular cartilage; 3b) Sagittal profile of knee without meniscus. Axial load distributed over articular cartilage only. With same force and smaller area of articulation, increased stress transmitted to articular cartilage.

#### **2.2 Patellofemoral compartments**

The patellofemoral articulation consists of the patella, the largest sesamoid in the human body, and the trochlea, a groove located on the anterior distal femur. The patella normally sits within a suprapatellar pouch in full extension and begins to engage the trochlea around 20 to 30 degrees of knee flexion. A vertically-oriented ridge on the articular surface of the patella separates the patella into medial and lateral facets. The superior 75% of the patella is articular cartilage, while the inferior 25% is non-articulating bone. The thickness of the articular cartilage in the patella can be the thickest in the human body, up to 5- or 6-mm (Scott 2005). This portends the ability to withstand high joint reactive forces seen in the patellofemoral articulation. The trochlea is separated into medial and lateral facets by a

Management of Knee Articular Cartilage Injuries 107

The calcified cartilage zone is a vascularized layer deep to the tidemark. This zone has a high calcium mineral content and low proteoglycan content. Although most of the collagen in articular cartilage is Type II (90% – 95%), there is a small amount of Type X collagen found in this zone, as it is associated with hypertrophic chondrocytes and calcification of cartilage. Beneath the calcified cartilage layer, separated by a thin cement line, is the subchondral bone, consisting of a lamellar cortical bony endplate and underlying cancellous

Chondrocytes produce the entirety of the content of the ECM, including proteoglycans, collagen, and non-collagenous proteins. Although proteoglycans represent only approximately 10% of the dry weight of articular cartilage, they give it most of its compressive strength(Ulrich-Vinther, Maloney et al. 2003). Glycosaminoglycans (GAGs), chondroitin sulfate (CS) and keratan sulfate (KS) bind to core protein which, in turn, binds to hyaluronic acid (HA) via link protein, forming an aggrecan proteoglycan molecule (Figure 5a). The negative charge associated with GAGs in aggrecan attracts water, thus attempting to increase tissue swelling. However, the collagen fiber network interconnections prevent swelling and tissue pressure increases (Figure 5b). This property is unique and

Fig. 4. 4) Schematic depiction of chondrocyte and collagen fibril distribution within the layers of articular cartilage (reproduced with permission from Ulrich-Vinther M, et al: Articular cartilage biology, in *Journal of the American Academy of Orthopaedic Surgeons* 2003;

gives articular cartilage its resilience to compression and deformation.

trabeculae(Madry, van Dijk et al. 2010).

11: 422. Publisher AAOS)

vertically-oriented trough that continues inferiorly into the intercondylar notch. The lateral facet of the trochlea extends anteriorly slightly more than that of the medial facet, providing a lateral buttress to patellar instability. The bony articular congruity attained by the patella and trochlea provides inherent static stability to the patellofemoral articulation.

The biomechanics of the patellofemoral joint are dependent upon both bony and soft tissue constraints. The patella engages the trochlea at approximately 20 degrees of knee flexion. At this position, the medial patellofemoral ligament functions as a primary restraint to lateral patellar translation(Conlan, Garth et al. 1993). With increasing flexion, the patella contacts the trochlea via a horizontal area of contact. Near extension, the inferior articular surface of the patella is "articulating." With increasing flexion, the horizontal contact area moves further proximal on the patella until this area is divided into two separate areas of contact on the medial and lateral femoral condyles at around 120 degrees of flexion. Contact pressure in the patellofemoral joint is greatest between 60 and 90 degrees of flexion, with maximum pressures of up to 12 MPa attained during forceful extensor mechanism quadriceps contractions(Huberti and Hayes 1984).

#### **2.3 Microscopic anatomy**

The microscopic composition of articular cartilage appears as a highly-organized, layered system of cells and extracellular matrix (ECM). The chondrocyte is the only cell present in articular cartilage and occupies only 5% of its total volume(Lieberman 2009). Thus, this cell is exclusively responsible for maintenance of the ECM. It receives its nutrition from synovial fluid diffusion from the interior of the joint. Embedded within the ECM, the chondrocyte is relatively immunoprivileged. This isolation also accompanies a lack of vascular or nerve connections, or lymphatic drainage. Thus, cartilage has a limited innate healing capacity.

Articular cartilage can be broadly grouped into two separate layers of uncalcified and calcified cartilage (Figure 4). More superficially, the uncalcified region may be divided into three zones: Superficial (tangential), transitional (or intermediate / middle), and deep (or radial). The superficial zone contains thin, elongated chondrocytes and collagen fibrils that parallel the articular surface. The primary function of this layer is tensile strength. An acellular clear film composed of collagen fibrils, the lamina splendens, is the articulating surface of the superficial zone visible upon gross or arthroscopic inspection. Given its proximity to the joint surface, the water content in the superficial zone is not surprisingly the highest amongst the layers (~80%). Proteoglycan content is lowest in this zone.

The transitional zone occupies approximately 50% of the thickness of uncalcified cartilage. This intermediate layer demonstrates thicker, more obliquely oriented collagen fibers. Compared to the superficial zone, the transitional zone has less water and collagen and greater proteoglycan content. Further, chondrocytes in this zone are more round with higher metabolic activity, evidenced by increasing numbers of intracellular organelles like mitochondria, endoplasmic reticulum, and Golgi membranes(Scott 2005).

The deep zone has the lowest water content (65%) of the uncalcified cartilage layers, reflecting its distance from the articular surface. Although the collagen content is lowest, the fiber diameter is greatest in this zone. The fibers are oriented perpendicular to the joint surface, anchoring the uncalcified cartilage layers to the calcified cartilage zone beneath across the undulating tidemark, the threshold of vascular penetration of the underlying subchondral bone. Proteoglycan content is highest in the deep zone. Chondrocytes are round and arranged in vertical columns.

vertically-oriented trough that continues inferiorly into the intercondylar notch. The lateral facet of the trochlea extends anteriorly slightly more than that of the medial facet, providing a lateral buttress to patellar instability. The bony articular congruity attained by the patella

The biomechanics of the patellofemoral joint are dependent upon both bony and soft tissue constraints. The patella engages the trochlea at approximately 20 degrees of knee flexion. At this position, the medial patellofemoral ligament functions as a primary restraint to lateral patellar translation(Conlan, Garth et al. 1993). With increasing flexion, the patella contacts the trochlea via a horizontal area of contact. Near extension, the inferior articular surface of the patella is "articulating." With increasing flexion, the horizontal contact area moves further proximal on the patella until this area is divided into two separate areas of contact on the medial and lateral femoral condyles at around 120 degrees of flexion. Contact pressure in the patellofemoral joint is greatest between 60 and 90 degrees of flexion, with maximum pressures of up to 12 MPa attained during forceful extensor mechanism

The microscopic composition of articular cartilage appears as a highly-organized, layered system of cells and extracellular matrix (ECM). The chondrocyte is the only cell present in articular cartilage and occupies only 5% of its total volume(Lieberman 2009). Thus, this cell is exclusively responsible for maintenance of the ECM. It receives its nutrition from synovial fluid diffusion from the interior of the joint. Embedded within the ECM, the chondrocyte is relatively immunoprivileged. This isolation also accompanies a lack of vascular or nerve connections, or lymphatic drainage. Thus, cartilage has a limited innate healing capacity. Articular cartilage can be broadly grouped into two separate layers of uncalcified and calcified cartilage (Figure 4). More superficially, the uncalcified region may be divided into three zones: Superficial (tangential), transitional (or intermediate / middle), and deep (or radial). The superficial zone contains thin, elongated chondrocytes and collagen fibrils that parallel the articular surface. The primary function of this layer is tensile strength. An acellular clear film composed of collagen fibrils, the lamina splendens, is the articulating surface of the superficial zone visible upon gross or arthroscopic inspection. Given its proximity to the joint surface, the water content in the superficial zone is not surprisingly

the highest amongst the layers (~80%). Proteoglycan content is lowest in this zone.

mitochondria, endoplasmic reticulum, and Golgi membranes(Scott 2005).

round and arranged in vertical columns.

The transitional zone occupies approximately 50% of the thickness of uncalcified cartilage. This intermediate layer demonstrates thicker, more obliquely oriented collagen fibers. Compared to the superficial zone, the transitional zone has less water and collagen and greater proteoglycan content. Further, chondrocytes in this zone are more round with higher metabolic activity, evidenced by increasing numbers of intracellular organelles like

The deep zone has the lowest water content (65%) of the uncalcified cartilage layers, reflecting its distance from the articular surface. Although the collagen content is lowest, the fiber diameter is greatest in this zone. The fibers are oriented perpendicular to the joint surface, anchoring the uncalcified cartilage layers to the calcified cartilage zone beneath across the undulating tidemark, the threshold of vascular penetration of the underlying subchondral bone. Proteoglycan content is highest in the deep zone. Chondrocytes are

and trochlea provides inherent static stability to the patellofemoral articulation.

quadriceps contractions(Huberti and Hayes 1984).

**2.3 Microscopic anatomy** 

The calcified cartilage zone is a vascularized layer deep to the tidemark. This zone has a high calcium mineral content and low proteoglycan content. Although most of the collagen in articular cartilage is Type II (90% – 95%), there is a small amount of Type X collagen found in this zone, as it is associated with hypertrophic chondrocytes and calcification of cartilage. Beneath the calcified cartilage layer, separated by a thin cement line, is the subchondral bone, consisting of a lamellar cortical bony endplate and underlying cancellous trabeculae(Madry, van Dijk et al. 2010).

Chondrocytes produce the entirety of the content of the ECM, including proteoglycans, collagen, and non-collagenous proteins. Although proteoglycans represent only approximately 10% of the dry weight of articular cartilage, they give it most of its compressive strength(Ulrich-Vinther, Maloney et al. 2003). Glycosaminoglycans (GAGs), chondroitin sulfate (CS) and keratan sulfate (KS) bind to core protein which, in turn, binds to hyaluronic acid (HA) via link protein, forming an aggrecan proteoglycan molecule (Figure 5a). The negative charge associated with GAGs in aggrecan attracts water, thus attempting to increase tissue swelling. However, the collagen fiber network interconnections prevent swelling and tissue pressure increases (Figure 5b). This property is unique and gives articular cartilage its resilience to compression and deformation.

Fig. 4. 4) Schematic depiction of chondrocyte and collagen fibril distribution within the layers of articular cartilage (reproduced with permission from Ulrich-Vinther M, et al: Articular cartilage biology, in *Journal of the American Academy of Orthopaedic Surgeons* 2003; 11: 422. Publisher AAOS)

Management of Knee Articular Cartilage Injuries 109

1986; Burr and Radin 2003). With increasing defect size, these osteocartilaginous changes

Fig. 6. Well-shouldered, small full-thickness chondral defect with no contact on underlying subchondral bone (left); larger full-thickness defect exhibits subchondral bone contact by the

Orthopaedic Surgeons in: Jones D and Peterson L: Autologous chondrocyte implantation, Lecture in *Journal of Bone and Joint Surgery, American* 2006; 88A(11): 2503. Publisher AAOS)

opposing surface (reproduced with permission from The American Academy of

Fig. 7. International Cartilage Repair Society (ICRS) cartilage injury classification

permission from the ICRS).

**3.2 Classification systems** 

(reproduced from the ICRS Cartilage Injury Evaluation Package [www.cartilage.org], with

The two most commonly used classification systems for arthroscopic analysis of chondral defects in the knee are the Outerbridge system and the International Cartilage Repair Society (ICRS) system (Figure 7). The Outerbridge system grades defects I – IV(Outerbridge 1961). Grade 1 lesions exhibited softening or swelling of cartilage; Grades 2 and 3 both exhibit fragmentation and fissuring of cartilage, with Grade 2 being less than ½ inch and Grade 3 being greater than ½ inch diameter; Grade 4 defects exhibit subchondral bone exposure. The newer ICRS system(Brittberg and Winalski 2003) is advantageous as it

can only be more greatly accelerated(Flanigan, Harris et al. 2010).

Fig. 5. 5a) Proteoglycan aggrecan molecule composed of chondroitin (CS) and keratan sulfate (KS) glycosaminoglycans, a protein core, and link protein attached to hyaluronic acid (HA) chain; 5b) ECM structure of collagen fibrils intertwined in aggrecan molecules (reproduced with permission from Ulrich-Vinther M, et al: Articular cartilage biology, in *Journal of the American Academy of Orthopaedic Surgeons* 2003; 11: 423. Publisher AAOS)
