Secondary Logo

Journal Logo

Articular Cartilage Injuries

Buckwalter, J., A.

Clinical Orthopaedics and Related Research: September 2002 - Volume 402 - Issue - p 21-37
SECTION I SYMPOSIUM: SPORTS MEDICINE
Free
SDC

The acute and repetitive impact and torsional joint loading that occurs during participation in sports can damage articular surfaces causing pain, joint dysfunction, and effusions. In some instances, this articular surface damage leads to progressive joint degeneration. Three classes of chondral and osteochondral injuries can be identified based on the type of tissue damage and the repair response: (1) damage to the joint surface that does not cause visible mechanical disruption of the articular surface, but does cause chondral damage and may cause subchondral bone injury; (2) mechanical disruption of the articular surface limited to articular cartilage; and (3) mechanical disruption of articular cartilage and subchondral bone. In most instances, joints can repair damage that does not disrupt the articular surface if they are protected from additional injury. Mechanical disruption of articular cartilage stimulates chondrocyte synthetic activity, but it rarely results in repair of the injury. Disruption of subchondral bone stimulates chondral and bony repair, but it rarely restores an articular surface that duplicates the biologic and mechanical properties of normal articular cartilage. In selected patients, surgeons have used operative treatments including penetrating subchondral bone, soft tissue grafts, and cell transplants and osteochondral autografts and allografts to restore articular surfaces after chondral injuries. Experimental studies indicate that use of artificial matrices and growth factors also may promote formation of a new joint surface. However, an operative treatment of an articular surface injury that will benefit patients must not just provide a new joint surface, it must produce better long-term joint function than would be expected if the injury was left untreated or treated by irrigation and debridement alone. Therefore, before selecting a treatment for a patient with an articular cartilage injury, the surgeon should define the type of injury and understand its likely natural history.

From the University of Iowa Department of Orthopaedics, Iowa City, IA.

Reprint requests to Joseph A. Buckwalter, MD, 01008 Pappajohn Pavilion, Department of Orthopaedics, University of Iowa College of Medicine, Iowa City, IA 52242.

DOI: 10.1097/01.blo.0000026073.30435.dc

List of Abbreviations Used: BMP bone morphogenetic protein, ECM extracellular matrix, FGF fibroblast growth factor, IGF-1 insulinlike growth factor-1, PDGF platelet-derived growth factor, PG proteoglycan, TGF-β transforming growth factor-beta

Normal pain-free movement depends on the unique properties of the articular cartilage that forms the bearing surfaces of synovial joints. 24 Damage or degeneration of this remarkable tissue decreases mobility and frequently causes pain with movement, and in the most severe instances, chronic pain. 27 The mechanisms, frequency, and natural history of articular surface injuries are understood poorly. 12,14,25 Limited awareness of chondral and osteochondral injuries and difficulty in diagnosing these injuries makes it impossible to accurately determine their incidence or their relationship to the development of joint degeneration. 21,22,25 However, arthroscopic examinations of injured knees suggest that closed articular surface injuries occur frequently. 91,92 One group of surgeons arthroscopically examined 85 knees with traumatic hemarthrosis but absent or negligible ligamentous instability. 91 Twenty percent of these knees had chondral fractures or articular surface defects. In many patients cartilage injuries occur in association with injuries to other tissues of the synovial joint including menisci, ligaments, joint capsule, and synovium. In these people the cartilage injury may be overlooked, and even when it is identified it is difficult to distinguish the effects of the cartilage injury from the effects of the injuries to other the other tissues. Damage to articular surfaces that does not result in visible disruption of articular cartilage or subchondral bone is not detected easily, although it probably occurs far more frequently than chondral and osteochondral fractures. 12 Several studies show that magnetic resonance imaging (MRI) may be useful in the diagnosis of these types of injuries. 62,104,109

Recent advances in methods of diagnosing articular surface injuries including arthroscopy and MRI combined with reports of new methods of stimulating cartilage repair or regeneration and osteochondral transplantation have increased interest in these injuries. Clinical evaluation of patients with articular surface damage and determining the appropriate role of these new treatments, or the need for any surgical treatment, requires understanding of the mechanisms of these injuries and their natural history. The current author discusses the mechanisms of closed articular surface injuries, the responses of articular surfaces to injury, current approaches to treatment of these injuries, and the evaluation of the results of these treatments.

Back to Top | Article Outline

Mechanisms of Articular Cartilage Injuries

Understanding of the mechanisms of articular surface injuries requires appreciation of how loads and rate of loading affect articular cartilage. Slowly applied loads and suddenly applied loads differ considerably in their effects. The articular cartilage ECM consists of water and a macromolecular framework formed primarily by collagens and large aggregating PGs. 24 The collagens give the tissue its form and tensile strength and the interaction of aggregating PGs with water give the tissue its stiffness to compression, resilience, and probably its durability. Loading of articular surfaces causes movement of fluid within the articular cartilage matrix that dampens and distributes loads within the cartilage and to the subchondral bone. 88 When this occurs slowly, the fluid movement allows the cartilage to deform and decreases the force applied to the matrix macromolecular framework. When it occurs too rapidly for fluid movement through the matrix and deformation of the tissue, as with sudden impact or torsional joint loading of the joint surface, the matrix macromolecular framework sustains a greater share of the force. If this force is great enough it ruptures the matrix macromolecular framework, damages cells, and exceeds the ability of articular cartilage to prevent subchondral bone damage by dampening and distributing loads.

In vivo, expected and unexpected and slow and sudden movements or impacts may differ in the amount of force transmitted to joint surfaces. Muscle contractions absorb much of the energy and stabilize joints during slow expected movements or impacts. Sudden or unexpected movements or impacts may occur too rapidly for muscle contractions to stabilize joints and decrease the forces on the articular surfaces. For this reason, sudden and unexpected movements or impacts can transmit greater forces to joint surfaces.

Acute or repetitive blunt joint trauma can damage articular cartilage and the calcified cartilage zone-subchondral bone region while leaving the articular surface intact. 12,39,71,113,124 The intensity and type of joint loading that can cause chondral and subchondral damage without visible tissue disruption has not been well defined. Physiologic levels of joint loading do not seem to cause joint injury, but impact loading above that associated with normal activities, but less than that necessary to produce cartilage disruption, can cause alterations of the cartilage matrix and damage chondrocytes. 12,39,60,61,71,113 Experimental evidence shows that loss of PGs or alteration of their organization (in particular, a decrease in PG aggregation) occurs before other signs of cartilage injury after impact loading. The loss of PGs may be attributable to increased degradation of the molecules or decreased synthesis. Significant loss of matrix PGs decreases cartilage stiffness and increases its permeability. These alterations may cause greater loading of the remaining macromolecular framework, including the collagen fibrils, increasing the vulnerability of the tissue to additional damage from loading. These injuries may cause other matrix abnormalities besides loss of PGs, such as distortions of the collagen fibril meshwork or disruptions of the collagen fibril PG relationships and swelling of the matrix, 39 and they may injure chondrocytes. 12,71

Currently there is no clinically applicable method of detecting alterations in cartilage matrix composition such as decreased PG concentration or increased water concentration; however, new imaging techniques may provide methods of assessing articular cartilage composition. When probing the articular surface, surgeons sometimes find regions of apparent softening that may result from alterations in the matrix, and devices are being developed that will allow in vivo measurement of articular surface stiffness. Combined with information about cartilage composition, these measurements may make it possible to better define injuries to the articular surface that do not result in visible tissue disruption.

Disrupting a normal articular surface with one impact requires substantial force, presumably because of the ability of articular cartilage and subchondral bone to dampen and distribute loads. A transarticular load of 2170 N applied to patellofemoral joints in canines caused fractures in the zone of calcified cartilage visible by light microscopy and articular cartilage fissures that extended from the articular surface to the transitional or superficial radial zone of the articular cartilage. 113 A study of the response of articular cartilage from humans to blunt trauma showed that articular cartilage could withstand impact loads of as much as 25 N/mm2 (25 MPa) without apparent damage. Impact loads exceeding this level caused chondrocyte death and cartilage fissures. 101 The authors suggested that reaching a stress level that could cause cartilage damage required a force greater than that necessary to fracture the femur. Another study 52 measured the pressure on patellofemoral articular cartilage from humans during impact loading and found that impact loads less than the level necessary to fracture bone caused stresses greater than 25 MPa in some regions of the articular surface. With the knee flexed 90°, 50% of the load necessary to cause a bone fracture produced joint pressures greater than 25 MPa for approximately 20% of the patellofemoral joint. At 70% of the bone fracture load, approximately 35% of the contact area of the patellofemoral joint pressures exceeded 25 MPa and at 100% of the bone fracture load, 60% of the patellofemoral joint pressures exceeded 25 MPa. These latter results show that impact loads can disrupt cartilage without fracturing bone.

Other experimental investigations show that repetitive impact loads split articular cartilage matrix and initiate progressive cartilage degeneration. 38,120,121 Cyclic loading of cartilage samples from humans in vitro caused surface fibrillation, 120 and periodic impact loading of metacarpal phalangeal joints from bovines in vitro combined with joint motion caused degeneration of articular cartilage. 100 Repeated overuse of joints from rabbits in vivo combined with peak overloading caused articular cartilage damage including formation of chondrocyte clusters, fibrillation of the matrix, thickening of subchondral bone, and penetration of subchondral capillaries into the calcified zone of articular cartilage. 38 The extent of cartilage damage seemed to increase with longer periods of repetitive overloading, and deterioration of the cartilage continued after cessation of excessive loading. This latter finding suggests that some cartilage damage is not immediately visible.

An investigation of cartilage plugs also showed that repetitive loading disrupted the tissue and that the severity of the damage increased with increasing load and increasing number of loading cycles. 126 Two hundred fifty cycles of a 1000 psi compression load caused surface abrasions. Five hundred cycles produced primary fissures penetrating to calcified cartilage, and 1000 cycles produced secondary fissures extending from the primary fissures. After 8000 cycles the fissures coalesced and undermined cartilage fragments. Higher loads caused similar changes with fewer cycles. The experiments suggested that repetitive loading can propagate vertical cartilage fissures from the joint surface to calcified cartilage and extension of oblique fissures into areas of intact cartilage, extending the damage and creating cartilage flaps and free fragments.

Clinical studies have identified articular cartilage fissures, flaps, and free fragments, and changes in subchondral bone similar to those produced experimentally by single and repetitive impact loads. 12,67 In at least some patients, acute impact loading of the articular surface or twisting movements of the joint apparently caused these injuries. In other patients, the cartilage damage may have resulted from repetitive loading. Magnetic resonance imaging of joints soon after an acute impact or torsional load occasionally shows changes in subchondral bone consistent with damage to the zone of calcified cartilage and subchondral bone even when the articular surface is intact. 62,104,109,114

Clinical experience suggests that chondral fractures and osteochondral fractures result from similar impact and twisting joint injuries, but they tend to occur in different age groups, and some individuals may have a greater risk of chondral fractures. Chondral fractures generally occur in skeletally mature people, whereas osteochondral fractures typically occur in skeletally immature people or young adults. This difference may result from age-related changes in the mechanical properties of the articular surface including the uncalcified cartilage, the calcified cartilage zone, and the subchondral bone. That is, age-related alterations in the articular cartilage matrix decrease the tensile stiffness and strength of the superficial zone, and the calcified cartilage zone subchondral bone region mineralizes fully after completion of skeletal growth presumably creating a marked difference in mechanical properties between the uncalcified cartilage and the calcified cartilage subchondral bone region. Taken together these changes probably increase the risk of ruptures of the superficial cartilage matrix and of these ruptures extending to the calcified cartilage subchondral bone region. Genetically-determined abnormalities of the articular cartilage also may increase the risk of chondral ruptures from a given impact or torsional load, but the relationships between known genetic abnormalities of articular cartilage and cartilage properties have not been well-defined.

Back to Top | Article Outline

Response of Articular Cartilage to Injury

Articular surface injuries can be classified based on the type of tissue damage and the repair response: (1) cartilage matrix and cell injuries; that is, damage to the joint surface that does not cause visible mechanical disruption of the articular surface; (2) chondral fissures, flap tears, or chondral defects; that is, visible mechanical disruption of articular cartilage limited to articular cartilage; and (3) osteochondral injuries; that is, visible mechanical disruption of articular cartilage and bone. 12,25,30,31 (Table 1).

TABLE 1

TABLE 1

Back to Top | Article Outline

Matrix and Cell Injuries

Acute or repetitive blunt trauma including excessive impact loading can cause alterations in articular cartilage matrix including a decrease in PG concentration and possibly disruptions of the collagen fibril framework. The ability of chondrocytes to sense changes in matrix composition and synthesize new molecules makes it possible for them to repair damage to the macromolecular framework. 76 It is not clear at what point this type of injury becomes irreversible and leads to progressive loss of articular cartilage. Presumably, the chondrocytes can restore the matrix as long as the loss of matrix PG does not exceed what the cells can produce rapidly, whether the fibrillar collagen meshwork remains intact, and whether enough chondrocytes remain viable. When these conditions are not met the cells cannot restore the matrix, the chondrocytes will be exposed to excessive loads, and the tissue will degenerate.

Back to Top | Article Outline

Chondral Injuries

Acute or repetitive trauma can cause focal mechanical disruption of articular cartilage including fissures, chondral flaps or tears, and loss of a segment of articular cartilage. 12 The lack of blood vessels and lack of cells that can repair significant tissue defects limit the response of cartilage to injury. 28,30 Chondrocytes respond to tissue injury by proliferating and increasing the synthesis of matrix macromolecules near the injury; however, the newly-synthesized matrix and proliferating cells do not fill the tissue defect, and soon after injury the increased proliferative and synthetic activity ceases.

Back to Top | Article Outline

Osteochondral Injuries

Unlike injuries limited to cartilage, injuries that extend into subchondral bone cause hemorrhage, fibrin clot formation, and activate the inflammatory response. 28,30 Soon after injury, blood escaping from the damaged bone blood vessels forms a hematoma that temporarily fills the injury site. Fibrin forms within the hematoma and platelets bind to fibrillar collagen. A continuous fibrin clot fills the bone defect and extends for a variable distance into the cartilage defect. Platelets within the clot release vasoactive mediators and growth factors or cytokines (small proteins that influence multiple cell functions including migration, proliferation, differentiation, and matrix synthesis) including TGF-β and PDGF. Bone matrix also contains growth factors including TGF-β, BMP, PDGF, IGF-1, IGF-II, and possibly others. Release of these growth factors may have an important role in the repair of osteochondral defects. In particular, they probably stimulate vascular invasion and migration of undifferentiated cells into the clot and influence the proliferative and synthetic activities of the cells. Shortly after entering the tissue defect, the undifferentiated mesenchymal cells proliferate and synthesize a new matrix. Within 2 weeks of injury, some mesenchymal cells assume the rounded form of chondrocytes and begin to synthesize a matrix that contains Type II collagen and a relatively high concentration of PGs. These cells produce regions of hyalinelike cartilage in the chondral and bone portions of the defect. Six to 8 weeks after injury, the repair tissue within the chondral region of osteochondral defects contains many chondrocytelike cells in a matrix consisting of Type II collagen, PGs, some Type I collagen, and noncollagenous proteins. Unlike the cells in the chondral portion of the defect, the cells in the bony portion of the defect produce immature bone, fibrous tissue, and hyalinelike cartilage.

The chondral repair tissue typically has a composition and structure intermediate between hyaline cartilage and fibrocartilage; and it rarely, if ever, replicates the elaborate structure of normal articular cartilage. 20,24,25,31 Occasionally, the cartilage repair tissue persists unchanged or progressively remodels to form a functional joint surface, but in most large osteochondral injuries the chondral repair tissue begins to show evidence of depletion of matrix PGs, fragmentation and fibrillation, increasing collagen content, and loss of cells with the appearance of chondrocytes within 1 year or less. The remaining cells often assume the appearance of fibroblasts as the surrounding matrix comes to consist primarily of densely packed collagen fibrils. This fibrous tissue usually fragments and often disintegrates leaving areas of exposed bone. The inferior mechanical properties of chondral repair tissue may be responsible for its frequent deterioration. 25,28 Even repair tissue that successfully fills osteochondral defects is less stiff and more permeable than normal articular cartilage, and the orientation and organization of the collagen fibrils in even the most hyalinelike cartilage repair tissue does not follow the pattern seen in normal articular cartilage. In addition, the repair tissue cells may fail to establish the normal relationships between matrix macromolecules, in particular, the relationship between cartilage PGs and the collagen fibril network. The decreased stiffness and increased permeability of repair cartilage matrix may increase loading of the macromolecular framework during joint use resulting in progressive structural damage to the matrix collagen and PGs thereby exposing the repair chondrocytes to excessive loads, additionally compromising their ability to restore the matrix.

Clinical experience and experimental studies suggest that the success of chondral repair in osteochondral injuries may depend to some extent on the severity of the injury as measured by the volume of tissue or surface area of cartilage injured and the age of the individual. 18 Smaller osteochondral defects that do not alter joint function heal more predictably than larger defects that may change the loading of the articular surface. Potential age-related differences in healing of chondral and osteochondral injuries have not been investigated thoroughly, but bone heals more rapidly in children than in adults and the articular cartilage chondrocytes in skeletally immature animals show a better proliferative response to injury and synthesize larger PG molecules than those from mature animals. 32,33,74–76,79 Furthermore, a growing synovial joint has the potential to remodel the articular surface to decrease the mechanical abnormalities created by a chondral or osteochondral defect.

Back to Top | Article Outline

Promoting Repair of Articular Surfaces

Better understanding of articular cartilage injuries and recognition of the limitations of the natural repair responses have contributed to the recent interest in cartilage repair and regeneration. 12,23,26,28,30 In the past 3 decades, clinical and basic scientific investigations have shown that implantation of artificial matrices, growth factors, perichondrium, periosteum and transplanted chondrocytes and mesenchymal stem cells can stimulate formation of cartilaginous tissue in synovial joint osteochondral and chondral defects. 15,16,23,25,29,82

Back to Top | Article Outline

Penetration of Subchondral Bone

Experimental and clinical investigations show that penetration of subchondral bone leads to formation of fibrocartilaginous repair tissue on the articular surfaces of synovial joints. 18,23,65 In regions with full-thickness loss or advanced degeneration of articular cartilage, penetration of the exposed subchondral bone disrupts subchondral blood vessels leading to formation of a fibrin clot that fills the bone defect and usually covers the exposed bone surface. 18,23 If the surface is protected from excessive loading, undifferentiated mesenchymal cells migrate into the clot, proliferate, and differentiate into cells with the morphologic features of chondrocytes. 108 In most instances, during a period of 6 to 8 weeks they form bone in the osseous portion of the defect and fibrocartilaginous tissue in the chondral portion. 30,63,64 Initially, the chondral repair tissue can closely resemble articular cartilage in gross and light microscopic appearance, but it fails to fully duplicate the composition (especially the types and concentrations of collagens and PGs), structure and mechanical properties of normal articular cartilage, and in many instances it deteriorates with time. 25,28,30,31

Surgeons currently use various methods of penetrating subchondral bone to stimulate formation of a new cartilaginous surface including arthroscopic drilling and abrasion of the articular surface and making multiple small diameter defects or fractures with an awl or similar instrument, a method referred to as the microfracture technique. 23,63–65,67,112 Prospective controlled trials of these treatments have not been published, but several authors report that these procedures can decrease the symptoms caused by isolated articular cartilage defects and osteoarthritis of the knee in a majority of the patients. 42,44,63,64,67,111,112 One group of investigators described less successful results: they found 39% early failures in a series of 49 knees in 44 patients older than 50 years with osteoarthritis, and 47% failures at the time of followup. In many patients with radiographic evidence of thinning or complete loss of articular cartilage, abrasion followed by decreased joint loading led to an increase in the radiographic joint space. 63,64 Although this increase in radiographic joint space presumably results from the formation of a new articular surface, the development of this new articular surface does not necessarily result in symptomatic improvement. Bert 4 and Bert and Maschka 6 found that 51% of 59 patients with osteoarthritis who were treated with abrasion arthroplasty had evidence of increased radiographic joint space 2 years after treatment, but 31% of these individuals either had no symptomatic improvement or more severe symptoms.

Patients who have isolated chondral or osteochondral defects may have better results than patients with osteoarthritis. Unfortunately, many reports do not clearly distinguish patients with chondral defects in otherwise normal joints from those with early degenerative joint disease. Most patients with isolated chondral or osteochondral defects are younger, and the available information suggests that these lesions are not necessarily progressive and that the initial symptoms associated with an isolated chondral injury may resolve. 83,125 In one study, isolated chondral defects of the knee were identified by arthroscopy in 28 athletes who were younger than 40 years at the time of diagnosis. 83 Three defects were treated by drilling of subchondral bone, and the others were treated by irrigation, removal of loose bodies and shaving of fibrillated cartilage. At an average of 14 years after diagnosis, 12 knees had evidence of radiographic loss of cartilage in the injured compartment. Twenty-two patients had excellent or good knee function and 21 patients had returned to their preinjury levels of activity. In another series of athletes, the followup of 23 soccer players with isolated chondral defects of their knees who were treated by debridement and penetration to subchondral bone showed that they returned to competition at an average of 10.8 weeks after treatment. 67 Evaluation of 15 knees 1 year after treatment showed six excellent, nine good, and no fair or poor results. These two reports have multiple limitations, but they show the need for additional study of the natural history and outcomes of treatment of isolated chondral defects in young adults.

Despite the evidence that penetration of subchondral bone stimulates formation of fibrocartilaginous repair tissue, the value of this approach for patients with loss or degeneration of articular cartilage remains uncertain. No studies have shown a convincing correlation between formation of fibrocartilaginous repair tissue and decreased joint pain. Some reports describe symptomatic improvement in a majority of patients with cartilage degeneration 42,44,63,64,111 but others indicate that abrasion or drilling of subchondral bone does not benefit patients with osteoarthritis of the knee, and may increase symptoms. 4,5 In addition, the short periods of followup, lack of well-defined evaluations of outcomes, lack of prospective randomized controlled trials, and the possibility for a placebo effect, 87 or an improvement in symptoms attributable to joint irrigation and debridement alone, 35,40,47,69 make it difficult to define the clinical indications for penetration of subchondral bone to stimulate formation of a new articular surface.

Back to Top | Article Outline

Periosteal and Perichondrial Grafts

The potential benefits of periosteal and perichondrial grafts include introduction of a new cell population along with an organic matrix and some protection of the graft or host cells from excessive loading. Animal experiments and clinical experience show that perichondrial and periosteal grafts placed in articular cartilage defects can produce new cartilage. 23,105 Several authors described the use of periosteal grafts for the treatment of isolated chondral and osteochondral defects, and showed that these grafts can produce a new articular surface. 15,93,94 Other investigators have reported encouraging results with perichondrial grafts. 41,53 However, one study suggests that increasing patient age adversely affects the results of soft tissue grafts. Seradge et al 107 studied the results of rib perichondrial arthroplasties in 16 metacarpophalangeal joints and 20 proximal interphalangeal joints at a minimum of 3 years after surgery. Patient age was directly related to the results. One hundred percent of the patients in their twenties and 75% of the patients in their thirties had good results after metacarpophalangeal joint arthroplasties. Seventy-five percent of the patients in their teens and 66% of the patients in their twenties had good results after proximal interphalangeal joint arthroplasties. None of the patients older than 40 years had a good result with either type of arthroplasty. The clinical observation that perichondrial grafts produced the best results in younger patients 107 agrees with the concept that age may adversely affect the ability of undifferentiated cells or chondrocytes to form an articular surface or that with age the population of cells that can form an articular surface declines. 33,76,79

Back to Top | Article Outline

Cell Transplantation

Transplantation of cells grown in culture provides another method of introducing a new cell population into chondral and osteochondral defects. Experimental work has shown that chondrocytes and undifferentiated mesenchymal cells placed in articular cartilage defects survive and produce a new cartilage matrix. 25,116–118 In one investigation, 80% of experimental osteochondral defects in rabbits treated with allograft articular chondrocytes embedded in collagen gels filled with chondral repair tissue within 24 weeks, 117 and other studies have found similar results. 57,58,90,102 Brittberg 8 and Brittberg and colleagues 11 compared the results of treating chondral defects in patellar articular surfaces in rabbits with periosteal grafts alone, carbon fiber scaffolds and periosteum, autologous chondrocytes and periosteum, and autologous chondrocytes, carbon fiber scaffolds, and periosteum. They found that the addition of autologous chondrocytes improved the histologic quality and amount of repair tissue. Other studies have shown that cultured mesenchymal stem cells also can repair experimental osteochondral defects. 115,116,119 Despite these encouraging results, relatively few controlled experimental studies showing beneficial effects of cell transplants have been published; all of them have studied osteochondral healing in normal joints from animals, and none of the studies has shown that cell transplants can restore a normal articular cartilage surface.

In addition to these few animal experiments, orthopaedic surgeons have used autologous chondrocyte transplants for treatment of localized cartilage defects in young adults. 8,10,86,98 The surgeons arthroscopically harvest 200 to 300 mg of articular cartilage from an area of the patient’s normal articular cartilage. 86 Enzymatic digestion of the harvested tissue releases the cells that are grown in culture for 2 to 5 weeks. The surgeons then do an arthrotomy to cover the defect with a flap of periosteum and inject the cultured cells into the area of the defect under the periosteal flap. 10,86 Proponents of this procedure report that it produces satisfactory results, including the ability to return to demanding physical activities, in more than 90% of patients and that biopsy specimens of the tissue in the graft sites show hyalinelike cartilage repair. 86

These results indicate that chondrocyte transplantation combined with a periosteal graft can promote restoration of an articular surface in humans, but more work is needed to assess the function and durability of the new tissue and determine whether it improves joint function and delays or prevents joint degeneration. Furthermore, chondrocyte transplantation has not yet been compared with other methods of stimulating articular cartilage repair (including use of periosteal transplants alone) in prospective studies, and cell transplants have not been shown to be beneficial in the treatment of patients with osteoarthritis. 73 The age of the patient also may influence the results of chondrocyte transplantation. Several studies show that with increasing age articular cartilage chondrocytes in humans become senescent, 77,78 a process that would significantly compromise the ability of chondrocytes from older donors to form new tissue.

Back to Top | Article Outline

Growth Factors

Growth factors influence various cell activities including proliferation, migration, matrix synthesis, and differentiation. Many of these factors, including the FGFs, IGFs, and TGF-βs, have been shown to affect chondrocyte metabolism and chondrogenesis. 18,23 Bone matrix contains a variety of these molecules including TGF-βs, IGFs, BMPs, PDGFs, and others. 18,19 In addition, mesenchymal cells, endothelial cells, and platelets produce many of these factors. Therefore, osteochondral injuries and exposure of bone attributable to loss of articular cartilage may release these agents that affect the formation of cartilage repair tissue, and they probably have an important role in the formation of new articular surfaces after currently used surgical procedures including penetration of subchondral bone. Local treatment of chondral or osteochondral defects with growth factors has the potential to stimulate restoration of an articular surface. An experimental study of the treatment of partial-thickness cartilage defects with enzymatic digestion of PGs that inhibit adhesion of cells to articular cartilage followed by implantation of a fibrin matrix and timed release of TGF-β showed that this growth factor can stimulate cartilage repair. 54–56 The cells that filled the chondral defects migrated into the defects from the synovium and formed new cartilaginous tissue. Despite the promise of this approach, the wide variety of growth factors, their multiple effects, the interactions among them, the possibility that the responsiveness of cells to growth factors may decline with age 33,75,79,99 and the limited understanding of their effects in osteoarthritic joints make it difficult to develop a simple strategy for using these agents to treat patients with osteoarthritis. However, development of growth factor-based treatments for isolated chondral and osteochondral injuries and early cartilage degenerative changes in younger people appears promising.

Back to Top | Article Outline

Artificial Matrices

Treatment of chondral defects with growth factors or cell transplants requires a method of delivering and in most instances at least temporarily stabilizing the growth factors or cells in the defect. For these reasons, the success of these approaches often depends on an artificial matrix. In addition, artificial matrices may allow, and in some instances stimulate ingrowth of host cells, matrix formation, and binding of new cells and matrix to host tissue. 97 Investigators have found that implants formed from various biologic and nonbiologic materials including treated cartilage and bone matrices, collagens, collagens and hyaluronan, fibrin, carbon fiber, hydroxyapatite, porous polylactic acid, polytetrafluoroethylene, polyester, and other synthetic polymers facilitate restoration of an articular surface. 23,25 Lack of studies that directly compare different types of artificial matrices makes it difficult to evaluate their relative merits, but the available reports show that this approach may contribute to restoration of an articular surface. Treatment of osteochondral defects of the knee in humans produced a satisfactory result in 77% of 47 patients evaluated clinically and arthroscopically 3 years after surgery. 89 Brittberg and colleagues 9 also studied the use of carbon fiber pads for treatment of articular surface defects. They found good or excellent results in 83% of 36 patients at an average of 4 years after treatment.

Back to Top | Article Outline

Articular Cartilage Transplantation

Articular cartilage transplantation differs from methods that attempt to restore an articular surface by stimulating cartilage repair, in that intact normal articular cartilage is implanted in the defect. Osteochondral grafts have the advantage of providing a fully-formed articular cartilage matrix and the potential for transplanting viable chondrocytes that can maintain the matrix, 37,95,106 and they can restore subchondral bone and joint contour for patients with osteochondral defects or joint incongruity. Transplantation of articular cartilage as part of an osteochondral graft has been shown to be an effective method of replacing focal regions of damaged articular cartilage and decreasing joint pain. 3,7,17,25,36,37,45,48,49,72,81,84,85,96,122 The reasons for the effectiveness of cartilage transplants in relieving joint pain remains uncertain, but some of this effect may be attributable to removal of an innervated segment of subchondral bone and replacing it with a graft that lacks innervation. Decreasing local intraosseous pressure also may have a role.

Back to Top | Article Outline

Autografts

In a small number of patients, surgeons have replaced localized regions of damaged or lost articular surfaces with articular cartilage autografts harvested from the patella, femoral condyle, and proximal fibula. 7,34,59,66,96,103,122,123 Osteochondral patellar autografts used to replace portions of the tibial articular surface healed and provided satisfactory joint function for more than a decade. 59,122 Outerbridge and colleagues 96 treated osteochondral defects of the femoral condyle with patellar osteochondral grafts in 10 patients. They found that knee function had improved and symptoms were alleviated in all 10 patients at an average of 6.5 years after transplantation. Recently, techniques have been developed to harvest cylindrical osteochondral plugs from a normal articular surface and transplant these plugs into chondral and osteochondral defects. 7,50,51,80 Experience with this approach to the treatment of chondral defects in the knee has shown that small anterior defects in the femoral condyle can be treated arthroscopically; large defects and posterior defects usually require an arthrotomy. Surgeons use multiple plugs to graft large defects, mosaicplasty, and one or two plugs to treat small defects. Reports of the results of osteochondral plug autografts in small numbers of patients indicate that they decrease pain and improve joint function. 7,50,51,80 However, long-term results have not been reported, and the healing of the donor sites and the defects treated by mosaicplasty have not been studied thoroughly. In general, the limited availability of sites for harvest of osteochondral autografts restricts the use of this approach to treatment of relative small articular surface defects, and the healing of the chondral portion of the autograft to the adjacent articular cartilage remains a concern.

Back to Top | Article Outline

Allografts

Because of their greater availability, and because they can be prepared in any size, surgeons also have used osteochondral allografts to replace damaged segments of articular surfaces. 2,3,36,43,45,46,48,49,70,72,81,84,85 Clinical experience with fresh and frozen osteochondral allografts shows that these grafts can decrease joint pain, and that the osseous part of an allograft can heal to the host bone and the chondral part can function as an articular surface. As with autografts, consistent healing of the chondral part of the graft to the adjacent articular cartilage has not been shown. To date, the reviews of patients treated with osteochondral allografts for localized chondral or osteochondral defects have not identified transmission of disease from donors to recipients. Ghazavi et al 46 and Gross 48 evaluated the results of 126 fresh osteochondral allografts used to treat localized posttraumatic osteoarticular defects in the knee in 123 patients. Survivorship analysis showed that the success rate was 95% at 5 years, 71% at 10 years, and 66% at 20 years. Factors that increased the risk of graft failure included patient age of more than 50 years, articular surface defects on both sides of the joint, and joint malalignment. One group of investigators reported that frozen osteochondral allografts produce results that compare favorably with fresh allografts for the treatment of localized defects of the distal femoral articular surface. 43 This group emphasized that use of frozen allografts makes it possible to do the surgical reconstructions electively and allows time for more extensive testing of the donors for possible viral and bacterial infections.

Overall, the available studies show that osteochondral allografts can provide effective treatment of localized posttraumatic degenerative arthritis of the patella, posttraumatic arthritis, and traumatic defects of the tibial plateau and especially for osteochondritis dissecans and avascular necrosis of the femoral condyle in younger patients. These procedures have not been predictably effective in treatment of articular cartilage loss or damage involving both the sides of a synovial joint or in patients with osteoarthritis.

Back to Top | Article Outline

Evaluating Treatments of Articular Cartilage Injuries

Determining which methods have the greatest promise of restoring an articular surface and more importantly providing improved long-term joint function depends on comparing their results. 17 Yet, one of the problems faced by physicians and scientists in comparing the multiple methods of restoring an articular surface is the variability in experimental models and clinical applications. For example, species differ in the thickness and mechanical properties of their articular cartilage 1 and probably the type and quality of natural cartilage repair or effects of various methods of stimulating repair. Furthermore, methods that stimulate cartilage repair in a normal joint in an animal will not necessarily lead to similar success in an injured or osteoarthritic joint in humans. In humans, patient age, condition of the joint including stability, alignment and extent of degenerative change, loading and motion of the joint after treatment, activity level, body weight and genetically-determined differences in healing may affect results. 13,18,23

Considerable variability also exists in methods of measuring the results of treatments of articular cartilage injuries. The ultimate measure of a method of restoring an articular surface is the extent to which the method restores the long-term function of a synovial joint; that is, full painless low friction motion, distribution of loads across the joint, and durability. Two years provides a reasonable minimum time necessary to assess restoration of joint function, and 5 years or more of improved joint function is a reasonable expectation for any procedure that would have significant value for large numbers of people. However, requiring that a method of restoring articular cartilage show long-term restoration of joint function before proceeding with additional studies, refinements, and clinical trials would considerably delay development and clinical use of promising treatments. For this reason, short-term evaluation also is necessary. The available experimental evidence suggests that chondral and osteochondral repair tissue formation usually is complete in 6 weeks or less after an attempt to stimulate restoration of an articular surface, but that remodeling of the repair tissue may continue for many months and probably years. 18,23,28 Degeneration of well-formed articular cartilage repair tissue may occur within months, or years after apparent clinically successful improvement in joint function. 30 Therefore, the minimal time for short-term evaluation of cartilage repair for most methods is of 4 to 6 weeks, and for those methods that show promise at this earliest time another evaluation after 6 months would be desirable. The best short-term evaluation of a method of stimulating cartilage repair is the extent to which that method produces new tissue that restores joint function, structure, and an articular surface that duplicates the volume, shape, structure, composition, and mechanical properties of normal articular cartilage. Table 2 lists measures that can be used to evaluate the short-term results of attempts to restore an articular cartilage surface. In addition to these measures, one study suggests that expression of the PG epitope 7D4 distinguishes hyalinelike repair cartilage from normal articular cartilage and from fibrous repair cartilage in the early stages of articular cartilage repair, and that with maturation and remodeling of hyalinelike articular cartilage repair tissue the expression of 7D4 decreases. 68

TABLE 2

TABLE 2

It generally has been assumed that cartilaginous repair tissue that more closely resembles normal articular cartilage also will have mechanical properties that more closely resemble normal articular cartilage, and that the volume, morphologic features, and histochemical staining of repair tissue will correlate with the mechanical properties of the tissue. One study examined this latter assumption. 110 Spirt and colleagues, 110 using statistical evaluation of interrater reliability, progressively refined a semiquantitative scale for histologic evaluation of cartilage repair. This procedure produced a highly reliable scale for evaluation of cartilage repair consisting of four categories: thickness of the chondral repair tissue, degree of subchondral bone depression, intensity of safranin-O staining in the chondral repair tissue, and morphologic features of the cells in the chondral repair tissue. Comparison of scores on the refined articular cartilage repair scale with indentation stiffness of the repair tissue showed a strong correlation between better articular cartilage repair as measured by the scale and increased indentation stiffness: the scores on the scale accounted for more than 70% of the indentation stiffness of the repair tissue (r2 = .71, p < .002). The results of this study suggest that the minimal evaluation of articular cartilage repair tissue should include the volume or thickness of the chondral repair tissue, when appropriate the restoration of the subchondral bone structure, the morphologic features of the chondral repair tissue, and an estimate of the PG content of the chondral repair tissue.

Recent work shows that the potential for restoration of a damaged articular surface exists. Currently surgeons penetrate subchondral bone, insert periosteal and perichondral grafts, autologous chondrocytes, and osteochondral autografts and allografts with the intent of restoring an articular surface and decreasing symptoms. The results of these procedures vary considerably among patients and there is limited information concerning the long-term outcomes. However, it seems that patients who have degenerative changes in addition to an articular surface injury are less likely to benefit from attempts to restore an articular surface than patients who do not have degenerative changes. Clinical and experimental studies show that chondrocyte and mesenchymal stem cell transplantation, periosteal and perichondrial grafting, synthetic matrices, growth factors, and other methods have the potential to stimulate formation of a new articular surface. Lack of prospective controlled clinical studies makes it difficult to compare these approaches and to date, none of these methods has been shown to predictably restore a durable articular surface in an osteoarthritic joint. The available clinical and experimental evidence indicates that treatment of an articular surface injury should begin with a detailed analysis of the structural and functional abnormalities of the involved joint, and the patient’s expectations for future joint use. Based on this analysis, the surgeon should develop a treatment plan that may combine correction of mechanical abnormalities (including malalignment, instability, and intraarticular causes of mechanical dysfunction) and debridement of frayed and partially detached cartilage fragments. In selected patients who do not have extensive degenerative changes treatment may include limited penetration of subchondral bone or use of implants that may consist of a synthetic matrix that incorporates cells or use of osteochondral grafts. All of these operative treatments should be followed by a postoperative course of controlled loading and motion and avoidance of high intensity impact or torsional loading of the involved joint until the patient has regained muscle strength and joint function and there is evidence that the articular surface has been restored effectively.

Back to Top | Article Outline

References

1. Athanasiou KA, Rosenwasser MP, Buckwalter JA, Malinin TI, Mow VC: Interspecies comparisons of in situ intrinsic mechanical properties of distal femoral cartilage. J Orthop Res 9:330–340, 1991.
2. Bayne O, Langer F, Pritzker KP, Haupt J, Gross AE: Osteochondral allografts in the treatment of osteonecrosis of the knee. Orthop Clin North Am 16:727–740, 1985.
3. Beaver RJ, Mahomed M, Backstein D, et al: Fresh osteochondral allografts for post-traumatic defects in the knee: A survivorship analysis. J Bone Joint Surg 74B:105–110, 1992.
4. Bert JM: Role of abrasion arthroplasty and debridement in the management of osteoarthritis of the knee. Rheum Dis Clin North Am 19:725–739, 1993.
5. Bert JM: Abrasion arthroplasty. Oper Tech Orthop 7:294–299, 1997.
6. Bert JM, Maschka K: The arthroscopic treatment of unicompartmental gonarthrosis. J Arthroscopy 5:25–32, 1989.
7. Bobic V: Arthroscopic osteochondral autograft transplantation in anterior cruciate ligament reconstruction: A preliminary clinical study. Knee Surg Sports Traumatol Arthrosc 3:262–264, 1996.
8. Brittberg M: Cartilage Repair. PhD Thesis. Goteborg, Sweden, Goteborg University 1996.
9. Brittberg M, Faxen E, Peterson L: Carbon fiber scaffolds in the treatment of early knee osteoarthritis. Clin Orthop 307:155–164, 1994.
10. Brittberg M, Lindahl A, Nilsson A, et al: Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. New Engl J Med 331:889–895, 1994.
11. Brittberg M, Nilsson A, Lindahl A, Ohlsson C, Peterson L: Rabbit articular cartilage defects treated with autologous cultured chondrocytes. Clin Orthop 326:270–283, 1996.
12. Buckwalter JA: Mechanical Injuries of Articular Cartilage. In Finerman G (ed). Biology and Biomechanics of the Traumatized Synovial Joint. Park Ridge, IL, American Academy of Orthopaedic Surgeons 83–96, 1992.
13. Buckwalter JA: Activity vs. rest in the treatment of bone, soft tissue and joint injuries. Iowa Orthop J 15:29–42, 1995.
14. Buckwalter JA: Osteoarthritis and articular cartilage use, disuse and abuse: Experimental studies. J Rheumatol 22(Suppl 43):13–15, 1995.
15. Buckwalter JA: Cartilage researchers tell progress: Technologies hold promise, but caution urged. Am Acad Orthop Surg Bull 44:24–26, 1996.
16. Buckwalter JA: Regenerating articular cartilage: Why the sudden interest? Orthop Today 16:4–5, 1996.
17. Buckwalter JA: Evaluating methods of restoring cartilagenous articular surfaces. Clin Orthop 367(Suppl): 224–238, 1999.
18. Buckwalter JA, Einhorn TA, Bolander ME, Cruess RL: Healing of Musculoskeletal Tissues. In Rockwood CA, Green D (eds). Fractures. Philadelphia, Lippincott 261–304, 1996.
19. Buckwalter JA, Glimcher MM, Cooper RR, Recker R: Bone biology II: Formation, form, modeling and remodeling. J Bone Joint Surg 77A:1276–1289, 1995.
20. Buckwalter JA, Hunziker EB, Rosenberg LC, et al: Articular Cartilage: Composition and Structure. In Woo SL, Buckwalter JA (eds). Injury and Repair of the Musculoskeletal Soft Tissues. Park Ridge, IL, American Academy of Orthopaedic Surgeons 405–425, 1988.
21. Buckwalter JA, Lane NE: Aging, sports and osteoarthritis. Sports Med Arthrosc Rev 4:276–287, 1996.
22. Buckwalter JA, Lane NE: Athletics and osteoarthritis. Am J Sports Med 25:873–881, 1997.
23. Buckwalter JA, Lohmander S: Operative treatment of osteoarthrosis: Current practice and future development. J Bone Joint Surg 76A:1405–1418, 1994.
24. Buckwalter JA, Mankin HJ: Articular cartilage I: Tissue design and chondrocyte-matrix interactions. J Bone Joint Surg 79A:600–611, 1997.
25. Buckwalter JA, Mankin HJ: Articular cartilage II: Degeneration and osteoarthrosis, repair, regeneration and transplantation. J Bone Joint Surg 79A:612–632, 1997.
26. Buckwalter JA, Martin JA: Degenerative Joint Disease. In Clinical Symposia Ciba Summit, NJ, Geigy 2–32, 1995.
27. Buckwalter JA, Martin JA, Mankin HJ: Synovial joint degeneration and the syndrome of osteoarthritis. Instr Course Lect 49:481–489, 2000.
28. Buckwalter JA, Mow VC: Cartilage Repair in Osteoarthritis. In Moskowitz RW, Howell DS, Goldberg VM, Mankin HJ (eds). Osteoarthritis: Diagnosis and Management. Ed 2. Philadelphia, Saunders 71–107, 1992.
29. Buckwalter JA, Mow VC, Ratliff A: Restoration of injured or degenerated articular surfaces. J Am Acad Orthop Surg 2:192–201, 1994.
30. Buckwalter JA, Rosenberg LA, Hunziker EB: Articular Cartilage: Composition, Structure, Response to Injury, and Methods of Facilitation Repair. In Ewing JW (ed). Articular Cartilage and Knee Joint Function: Basic Science and Arthroscopy. New York, Raven Press 19–56, 1990.
31. Buckwalter JA, Rosenberg LC, Coutts R, et al: Articular Cartilage: Injury and Repair. In Woo SL, Buckwalter JA (eds). Injury and Repair of the Musculoskeletal Soft Tissues. Park Ridge, IL, American Academy of Orthopaedic Surgeons 465–482, 1988.
32. Buckwalter JA, Roughley PJ, Rosenberg LC: Age-related changes in cartilage proteoglycans: Quantitative electron microscopic studies. Microsc Res Tech 28:398–408, 1994.
33. Buckwalter JA, Woo SL-Y, Goldberg VM, et al: Soft tissue aging and musculoskeletal function. J Bone Joint Surg 75A:1533–1548, 1993.
34. Campanacci M, Cervellati C, Donati U: Autogenous patella as replacement for a resected femoral or tibial condyle: A report on 19 cases. J Bone Joint Surg 67B:557–563, 1985.
35. Chang RW, Falconer J, Stulberg SD, et al: A randomized, controlled trial of arthroscopic surgery versus closed-needle joint lavage for patients with osteoarthritis of the knee. Arthritis Rheum 36:289–296, 1993.
36. Convery FR, Meyers MH, Akeson WH: Fresh osteochondral allografting of the femoral condyle. Clin Orthop 273:139–145, 1991.
37. Czitrom AA, Keating S, Gross AE: The viability of articular cartilage in fresh osteochondral allografts after clinical transplantation. J Bone Joint Surg 72A:574–581, 1990.
38. Dekel S, Weissman SL: Joint changes after overuse and peak overloading of rabbit knees in vivo. Acta Orthop Scand 49:519–528, 1978.
39. Donohue JM, Buss D, Oegema TR, Thompson RC: The effects of indirect blunt trauma on adult canine articular cartilage. J Bone Joint Surg 65A:948–956, 1983.
40. Edelson R, Burks RT, Bloebaum RD: Short-term effects of knee washout for osteoarthritis. Am J Sports Med 23:345–349, 1995.
41. Engkvist O, Johansson SH: Perichondrial arthroplasty: A clinical study in twenty-six patients. Scand J Plast Reconstr Surg 14:71–87, 1980.
42. Ewing JW: Arthroscopic Treatment of Degenerative Meniscal Lesions and Early Degenerative Arthritis of the Knee. In Ewing JW (ed). Articular Cartilage and Knee Joint Function. Basic Science and Arthroscopy. New York, Raven Press 137–145, 1990.
43. Flynn JM, Springfield DS, Mankin HJ: Osteoarticular allografts to treat distal femoral osteonecrosis. Clin Orthop 303:38–43, 1994.
44. Friedman MJ, Berasi DO, Fox JM, et al: Preliminary results with abrasion arthroplasty in the osteoarthritic knee. Clin Orthop 182:200–205, 1984.
45. Garrett JC: Fresh osteochondral allografts for treatment of articular defects in osteochondritis dissecans of the lateral femoral condyle in adults. Clin Orthop 303:33–37, 1994.
46. Ghazavi MT, Pritzker KP, Davis AM, Gross AE: Fresh osteochondral allografts for post-traumatic osteochondral defects of the knee. J Bone Joint Surg 79B:1008–1013, 1997.
47. Gibson JNA, White MD, Chapman VM, Strachan RK: Arthroscopic lavage and debridement for osteoarthritis of the knee. J Bone Joint Surg 74B:534–537, 1992.
48. Gross AE: Fresh osteochondral allografts for post-traumatic knee defects: Surgical technique. Oper Tech Orthop 7:334–339, 1997.
49. Gross AE, Beaver RJ, Mohammed MN: Fresh Small Fragment Osteochondral Allografts Used for Posttraumatic Defects in the Knee Joint. In Finerman GAM, Noyes FR (eds). Biology and Biomechanics of the Traumatized Synovial Joint: The Knee as a Model. Rosemont, IL, American Academy of Orthopaedic Surgeons 123–141, 1992.
50. Hangody L, Kish G, Karpati Z, Szerb I, Eberhardt R: Treatment of osteochondritis dissecans of the talus: Use of the mosaicplasty technique: A preliminary report. Foot Ankle Int 18:628–634, 1997.
51. Hangody L, Kish G, Karpati Z, Eberhart R: Osteochondral plugs: Autogenous osteochondral mosaicplasty for the treatment of focal chondral and osteochondral articular defects. Oper Tech Orthop 7:312–322, 1997.
52. Haut RC: Contact pressures in the patellofemoral joint during impact loading on the human flexed knee. J Orthop Res 7:272–280, 1989.
53. Homminga GN, Bulstra SK, Bouwmeester PM, Linden AJVD: Perichondrial grafting for cartilage lesions of the knee. J Bone Joint Surg 72B:1003–1007, 1990.
54. Hunziker EB: Growth-factor-induced healing of partial-thickness defects in adult articular cartilage. Osteoarthritis Cartilage 9:22–32, 2001.
55. Hunziker EB, Rosenberg LC: Repair of partial-thickness defects in articular cartilage: Cell recruitment from the synovial membrane. J Bone Joint Surg 78A:721–733, 1996.
56. Hunziker EB, Rosenberg R: Induction of repair partial thickness articular cartilage lesions by timed release of TGF-Beta. Trans Orthop Res Soc 19:236, 1994.
57. Itay S, Abramovici A, Nevo Z: Use of cultured embryonal chick epiphyseal chondrocytes as grafts for defects in chick articular cartilage. Clin Orthop 220:284–303, 1987.
58. Itay S, Abramovici A, Ysipovitch Z, Nevo Z: Correction of defects in articular cartilage by implants of cultures of embryonic chondrocytes. Trans Orthop Res Soc 13:112, 1988.
59. Jacobs JE: Follow-up notes on articles previously published in the journal: Patellar graft for severely depressed comminuted fractures of the lateral tibial condyle. J Bone Joint Surg 47A:842–847, 1965.
60. Jeffrey JE, Gregory DW, Aspden RM: Matrix damage and chondrocyte viability following a single impact load on articular cartilage. Arch Biochem Biophys 10:87–96, 1995.
61. Jeffrey JE, Thomson LA, Aspden RM: Matrix loss and synthesis following a single impact load on articular cartilage in vitro. Biochem Biophys Acta 15:223–232, 1997.
62. Johnson DL, Urban WP, Caborn DN, Vanarthos WJ, Carlson CS: Articular cartilage changes seen with magnetic resonance imaging-detected bone bruises associated with anterior cruciate ligament rupture. Am J Sports Med 26:409–414, 1998.
63. Johnson LL: Arthroscopic abrasion arthroplasty: Historical and pathologic perspective: Present status. Arthroscopy 2:54–59, 1986.
64. Johnson LL: The Sclerotic Lesion: Pathology and the Clinical Response to Arthroscopic Abrasion Arthroplasty. In Ewing JW (ed). Articular Cartilage and Knee Joint Function. Basic Science and Arthroscopy. New York, Raven Press 319–333, 1990.
65. Johnson LL: Arthroscopic Abrasion Arthroplasty. In McGinty JB (ed). Operative Arthroscopy. Philadelphia, Lippincott-Raven 427–446, 1996.
66. Karpinski MR, Botting TD: Patellar graft for late disability following tibial plateau fractures. Injury 15:197–202, 1983.
67. Levy AS, Lohnes J, Sculley S, LeCroy M, Garrett W: Chondral delamination of the knee in soccer players. Am J Sports Med 24:634–639, 1996.
68. Lin P, Buckwalter JA, Olmstead M, Caterson B: Monoclonal antibody 7D4 is a marker for articular cartilage repair in rabbits and monkeys. Orthop Trans 18:262, 1993.
69. Livesley PJ, Doherty M, Needoff M, Moulton A: Arthroscopic lavage of osteoarthritic knees. J Bone Joint Surg 73B:922–926, 1991.
70. Locht RC, Gross AE, Langer F: Late osteochondral allograft resurfacing for tibial plateau fractures. J Bone Joint Surg 66A:328–335, 1984.
71. Loening AM, James IE, Levenston ME, et al: Injurious mechanical compression of bovine articular cartilage induces chondrocyte apoptosis. Arch Biochem Biophys 381:205–212, 2000.
72. Mahomed MN, Beaver RJ, Gross AE: The long-term success of fresh, small fragment osteochondral allografts used for intraarticular post-traumatic defects in the knee joint. Orthopedics 15:1191–1199, 1992.
73. Mankin HJ, Buckwalter JA: Restoring the osteoarthritic joint. J Bone Joint Surg 78A:1–2, 1996.
74. Martin JA, Buckwalter JA: Articular cartilage aging and degeneration. Sports Med Arthrosc Rev 4:263–275, 1996.
75. Martin JA, Buckwalter JA: Fibronectin and cell shape affect age related decline in chondrocyte synthetic response to IGF-I. Trans Orthop Res Soc 21:306, 1996.
76. Martin JA, Buckwalter JA: The role of chondrocyte-matrix interactions in maintaining and repairing articular cartilage. Biorheology 37:129–140, 2000.
77. Martin JA, Buckwalter JA: Roles of articular cartilage aging and chondrocyte senescence in the pathogenesis of osteoarthritis. Iowa Orthop J 21:1–7, 2001.
78. Martin JA, Buckwalter JA: Telomere erosion and senescence in human articular cartilage chondrocytes. J Gerontol Biol Sci 56:172–179, 2001.
79. Martin JA, Ellerbroek SM, Buckwalter JA: The age-related decline in chondrocyte response to insulin-like growth factor-I: The role of growth factor binding proteins. J Orthop Res 15:491–498, 1997.
80. Matsusue Y, Yamamuro T, Hama H: Arthroscopic multiple osteochondral transplantation to the chondral defect in the knee associated with anterior cruciate ligament disruption. Arthroscopy 9:318–321, 1993.
81. McDermott AG, Langer F, Pritzker KP, Gross AE: Fresh small-fragment osteochondral allografts: Long-term follow-up study on first 100 cases. Clin Orthop 197:96–102, 1985.
82. Messner K, Gillquist J: Cartilage repair: A critical review. Acta Orthop Scand 67:523–529, 1996.
83. Messner K, Maletius W: The long-term prognosis for severe damage to weight-bearing cartilage in the knee. Acta Orthop Scand 67:165–168, 1996.
84. Meyers MH: Resurfacing of the femoral head with fresh osteochondral allografts: Long-term results. Clin Orthop 197:111–114, 1985.
85. Meyers MH, Akeson W, Convery FR: Resurfacing the knee with fresh osteochondral allograft. J Bone Joint Surg 71A:704–713, 1989.
86. Minas T, Peterson L: Chondrocyte transplantation. Oper Tech Orthop 7:323–333, 1997.
87. Moseley JB, Wray NP, Kuykendall D, Willis K, Landon GC: Arthroscopic treatment of osteoarthritis of the knee: A prospective, randomized, placebo-controlled trial: Results of a pilot study. Am J Sports Med 24:28–34, 1996.
88. Mow VC, Rosenwasser MP: Articular Cartilage: Biomechanics. In Woo SL, Buckwalter JA (eds). Injury and Repair of the Musculoskeletal Soft Tissue. Park Ridge, IL, American Academy of Orthopaedic Surgeons 427–463, 1988.
89. Muckle DS, Minns RJ: Biological response to woven carbon fiber pads in the knee: A clinical and experimental study. J Bone Joint Surg 72B:60–62, 1990.
90. Noguchi T, Oka M, Fujino M, Neo M, Yamamuro T: Repair of osteochondral defects with grafts of cultured chondrocytes: Comparison of allografts and isografts. Clin Orthop 302:251–258, 1994.
91. Noyes FR, Bassett RW, Grood ES, Butler DL: Arthroscopy in acute traumatic hemarthrosis of the knee. J Bone Joint Surg 62A:687–695, 1980.
92. Noyes FR, Stabler CL: A system for grading articular cartilage lesions at arthroscopy. Am J Sports Med 17:505–513, 1989.
93. O’Driscoll SW, Keeley FW, Salter RB: Durability of regenerated articular cartilage produced by free autogenous periosteal grafts in major full-thickness defects in joint surfaces under the influence of continuous passive motion. J Bone Joint Surg 70A:595–606, 1988.
94. O’Driscoll SW, Salter RB: The repair of major osteochondral defects in joint surfaces by neochondrogenesis with autogenous osteoperiosteal grafts stimulated by continuous passive motion: An experimental investigation in the rabbit. Clin Orthop 208:131–140, 1986.
95. Ohlendorf C, Tomford WW, Mankin HJ: Chondrocyte survival in cryopreserved osteochondral articular cartilage. J Orthop Res 14:413–416, 1996.
96. Outerbridge HK, Outerbridge AR, Outerbridge RE: The use of lateral patellar autologous graft for the repair of a large osteochondral defect in the knee. J Bone Joint Surg 77A:65–72, 1995.
97. Paletta GA, Arnoczky SP, Warren RG: The repair of osteochondral defects using an exogenous fibrin clot: An experimental study in dogs. Am J Sports Med 20:725–731, 1992.
98. Peterson L: Articular cartilage injuries treated with autologous chondrocyte transplantation in the human knee. Acta Orthop Belg 62(Suppl 1):196–200, 1996.
99. Pfeilschifter J, Diel I, Brunotte K, Naumann A, Ziegler R: Mitogenic responsiveness of human bone cells in vitro to hormones and growth factors decreases with age. J Bone Miner Res 8:707–717, 1993.
100. Radin EL, Paul IL: Response of joints to impact loading: In vitro wear. Arthritis Rheum 14:356–362, 1971.
101. Repo RU, Finlay JB: Survival of articular cartilage after controlled impact. J Bone Joint Surg 59A:1068–1075, 1977.
102. Robinson D, Halperin N, Nevo Z: Regenerating hyaline cartilage in articular defects of old chickens using implants of embryonal chick chondrocytes embedded in a new natural delivery substance. Calcif Tissue Int 46:246–253, 1990.
103. Roffman M: Autogenous grafting for an osteochondral fracture of the femoral condyle: A case report. Acta Orthop Scand 66:571–572, 1995.
104. Rubin DA, Harner CD, Costello JM: Treatable chondral injuries of the knee: Frequency of associated focal subchondral edema. Am J Roentgenol 174:1099–1106, 2000.
105. Salter RB: Continuous Passive Motion CPM: A Biological Concept for the Healing and Regeneration of Articular Cartilage, Ligaments and Tendons, From Original Research to Clinical Applications. Baltimore, Williams and Wilkins, 1993.
106. Schachar N, McAllister D, Stevenson M, Novak K, McGann L: Metabolic and biochemical status of articular cartilage following cryopreservation and transplantation: A rabbit model. J Orthop Res 10:603–609, 1992.
107. Seradge H, Kutz JA, Kleinert HE, et al: Perichondrial resurfacing arthroplasty in the hand. J Hand Surg 9A:880–886, 1984.
108. Shapiro F, Koide S, Glimcher MJ: Cell origin and differentiation in the repair of full-thickness defects of articular cartilage. J Bone Joint Surg 75A:532–553, 1993.
109. Spindler KP, Schils JP, Bergfeld JA, et al: Prospective study of osseous, articular and meniscal lesions in recent anterior cruciate ligament tears by magnetic resonance imaging and arthroscopy. Am J Sports Med 21:551–557, 1993.
110. Spirt AA, Brand RA, Buckwalter JA, Mohler CG: Enhancing the reliability of a valid histologic grading scale for articular cartilage repair. Trans Orthop Res Soc 21:542, 1996.
111. Sprague NF: Arthroscopic debridement for degenerative knee joint disease. Clin Orthop 160:118–123, 1981.
112. Steadman JR, Rodkey WG, Singleton SB, Briggs KK: Microfracture technique for full-thickness chondral defects: Technique and clinical results. Oper Tech Orthop 7:294–299, 1997.
113. Thompson RC, Oegema TR, Lewis JL, Wallace L: Osteoarthritic changes after acute transarticular load: An animal model. J Bone Joint Surg 73A:990–1001, 1991.
114. Vellet AD, Marks PH, Fowler PJ, Mururo TG: Occult posttraumatic osteochondral lesions of the knee: Prevalence, classification, and short-term sequelae evaluated with MR imaging. Radiology 178:271–276, 1991.
115. Wakitani S, Goto T, Mansour JM, Goldberg VM, Caplan AI: Mesenchymal stem cell-based repair of a large articular cartilage and bone defect. Trans Orthop Res Soc 19:481, 1994.
116. Wakitani S, Goto T, Pineda SJ, et al: Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg 76A:579–592, 1994.
117. Wakitani S, Kimura T, Hirooka A, et al: Repair of rabbits’ articular surfaces by allograft of chondrocytes embedded in collagen gels. Trans Orthop Res Soc 13:440, 1988.
118. Wakitani S, Kimura T, Hirooka A, et al: Repair of rabbit articular surfaces with allograft chondrocytes embedded in collagen gel. J Bone Joint Surg 71B:74–80, 1989.
119. Wakitani S, Ono K, Goldberg VM, Caplan AI: Repair of large cartilage defects in weight-bearing and partial weight-bearing articular surfaces with allograft articular chondrocytes embedded in collagen gels. Trans Orthop Res Soc 19:238, 1994.
120. Weightman B: Tensile fatigue of human articular cartilage. J Biomech 9:193–200, 1976.
121. Weightman BO, Freeman MAR, Swanson SAV: Fatigue of articular cartilage. Nature 244:303–304, 1973.
122. Wilson WJ, Jacobs JE: Patellar graft for severely depressed comminuted fractures of the lateral tibial condyle. J Bone Joint Surg 34A:436–442, 1952.
123. Yamashita F, Sakakida K, Suzu F, Takai S: The transplantation of an autogenic osteochondral fragment for osteochondritis dissecans of the knee. Clin Orthop 201:43–50, 1985.
124. Zang H, Vrahas MS, Baratta RV, Rosler DM: Damage to rabbit femoral articular cartilage following direct impacts of uniform stresses: An in vitro study. Clin Biomech 14:543–548, 1999.
125. Zarins B, Parsons C: Chondral injuries: clinical overview. Oper Tech Orthop 7:345–346, 1997.
126. Zimmerman NB, Smith DG, Pottenger LA, Cooperman DR: Mechanical disruption of human patellar cartilage by repetitive loading in vitro. Clin Orthop 229:302–307, 1988.

Section Description

Kurt P. Spindler, MD; and Edward M. Wojtys, MD—Guest Editors

© 2002 Lippincott Williams & Wilkins, Inc.