**3. Cartilage injury**

Partial and full thickness cartilage defects have a limited ability for healing. This is in part attributed to the avascular properties of cartilage, limited stem cell population, as well as the hypoxic environment of diarthrodial joints. Additionally the mechanical loads in the joint can make articular cartilage healing a challenge. The full natural history of full thickness chondral defects is not well documented in the literature. However it is thought that full thickness defects left untreated lead to joint space narrowing and degenerative arthritis (Messner & Maletius, 1996).

Cartilage injuries can occur with a twisting, shearing type injury in combination with axial loading. These defects are commonly associated with concomitant knee pathology such as meniscus tears, anterior cruciate ligament tears, medial collateral or lateral collateral ligament tears. There is a 5-10% incidence of full thickness chondral lesions following acute hemarthrosis (Noyes et al, 1980). In athletes, there is approximately a 36% prevalence of full thickness focal chondral defects, with 14% being asymptomatic (Flanigan et al, 2010).

Patients who have symptomatic chondral lesions typically present with pain localized to the compartment of injury, increased with weight-bearing of that compartment. They may also have recurrent effusions, catching, locking, or other mechanical symptoms. The physical examination typically will demonstrate crepitance, joint effusion, tenderness along ipsilateral

Articular Cartilage Regeneration with Stem Cells 133

In 1959, abrasion arthroplasty was developed by Pridie to address chondral defects (Pridie, 1959). Originally developed as an open procedure, it was later adapted for arthroscopy by Johnson (Johnson, 1986). Today, abrasion arthroplasty is used primarily for osteoarthritic knees. However, for small focal chondral defects, microfracture is most commonly used. Microfracture is a marrow stimulating technique that penetrates the subchondral bone in the cartilage defect (Fig 4). This allows marrow to communicate with the cartilage defect populating it with MSC, inflammatory mediators, and blood. This technique is simple to perform and has good to excellent clinical results (Gill, 2000; Steadman et al, 2003; Asik et al, 2008). Postoperative management requires prolonged non-weight-bearing (4 to 6 weeks) followed by the use of continuous passive motion. However, microfracture generates fibrocartilage in the defect and has a shorter functional lifespan compared with hyaline

Fig. 4. Marrow stimulation with: (A) microfracture provides a source of (B) blood cells and bone marrow mesenchymal stem cells for cartilage regeneration. Healing response typically

Other techniques to address focal cartilage defects are osteoarticular transfer system with auto/allograft transplantation (OATS). This technique involves transplanting the defect with an intact cartilage and subchondral bone plug. This technique is typically used for small to medium sized lesions (0.5-3cm2) (Fig 5). If a larger area is to be addressed a mosaicplasty is performed with multiple plugs. The main disadvantages are donor site morbidity, breakdown between the implanted cartilage and subchondral bone, gaps that

More recently autologous chondrocyte implantation (ACI) was developed to regenerate cartilage closer to hyaline cartilage. This technique can be used for larger defects (2-10 cm2), in patients who are symptomatic, and primarily located on the femoral condyles. To perform ACI requires 2 stages. The first stage involves harvesting cartilage from a biopsy to acquire cartilage cells. These cells are cultured to produce expanded autologous chondrocytes, which are subsequently implanted in the defect and held in place with a periosteal patch or collagen sheet sewn in place and sealed with a fibrin glue (Gooding et al, 2006). The postoperative course is challenging with a prolonged course of protected weightbearing and continuous passive motion for 4 to 6 weeks. It can take up to 1-1.5 years for larger lesions to fill in. Second generation ACI is currently undergoing development to overcome the technical disadvantages of the first generation. Second generation ACI uses

cartilage (Menche et al, 1996; McGuire et al, 2002; Steinwachs et al, 2008).

**4. Cartilage regeneration methods** 

results in fibrocartilage formation.

remain between plugs, as well as technical difficulty.

joint line, signs of concomitant injury (meniscus or ligamentous), or malalignment. Coexisting malalignment can contribute to chondral injuries, i.e. patella maltracking, high Q angle, tight lateral patellar retinaculum, or varus/valgus alignment (Fig 3) (Freedman et al, 2004).

Fig. 2. This figure demonstrates how cartilage can be visualized differently with varying histological stains. From left to right: hemotoxylin & eosin (H&E) shows cellular content, Safranin-O highlights proteoglycan content, Masson's Trichrome shows collagen fibers and orientation of fibers, and immunohistochemistry can illustrate the different collagen types. Histological stains provide visualization and qualitative analysis of cartilage.

Fig. 3. Illustration of lateral patellar maltracking and its effects on chondral wear in the patellofemoral joint. (A) Radiograph with lateral patella maltracking, and (B) arthroscopic view showing chondral injury in a patient with lateral patella maltracking and the "kissing lesion" associated.

joint line, signs of concomitant injury (meniscus or ligamentous), or malalignment. Coexisting malalignment can contribute to chondral injuries, i.e. patella maltracking, high Q angle, tight

lateral patellar retinaculum, or varus/valgus alignment (Fig 3) (Freedman et al, 2004).

Fig. 2. This figure demonstrates how cartilage can be visualized differently with varying histological stains. From left to right: hemotoxylin & eosin (H&E) shows cellular content, Safranin-O highlights proteoglycan content, Masson's Trichrome shows collagen fibers and orientation of fibers, and immunohistochemistry can illustrate the different collagen types.

Fig. 3. Illustration of lateral patellar maltracking and its effects on chondral wear in the patellofemoral joint. (A) Radiograph with lateral patella maltracking, and (B) arthroscopic view showing chondral injury in a patient with lateral patella maltracking and the "kissing

lesion" associated.

Histological stains provide visualization and qualitative analysis of cartilage.
