**4. Clinical strategies for the osteochondral therapeutic approach**

The injuries in the articular cartilage are able to stimulate a significant musculoskeletal morbidity not only in elderly patients but also in young people.

The restoration of damage from joint injuries to date represents a great challenge for medicine, since it cannot regenerate spontaneously; moreover, over time it can also lead to the establishment of osteoarthritis (OA).

 The classification of articular cartilage injury is performed by instrumented palpation of the lesion and by direct observation by arthroscopy [15, 16]. The most complete classification system is established by the International Cartilage Repair Society (ICRS) [17]. The ICRS grading system evaluates the depth of the lesion and the degree to which the subchondral bone is involved to classify the injury as follows: grade 0 corresponds to a normal joint; grade 1 is presented by superficial lesions, soft cleft, and/or superficial fissures and cracks; grade 2 for abnormal lesions that extend to <50% of the depth of the cartilage; grade 3 due to serious abnormalities in which cartilage defects extend to >50% of the depth of the cartilage, as well as to the calcified layer and up to, but not through, the subchondral bone; and grade 4 for severe abnormal where there is also development of blisters in the tissue [17].

Articular cartilage has a limited capacity for repair. Injured chondrocytes (either superficial or partial thickness lesions) from the early stages develop *Therapeutic Potential of Articular Cartilage Regeneration using Tissue Engineering Based… DOI: http://dx.doi.org/10.5772/intechopen.84697* 

defects in their metabolism; therefore, they are unable to maintain a normal concentration of PGs [18].

These modifications trigger the increase in tissue hydration and therefore the fibrillar disorganization of collagen [3, 19]. These changes favor an increase in the transmission of force toward the subchondral bone. By exceeding the capacity of the subchondral bone, the impact on the damaged cartilage is even deeper.

In response to this series of events, the chondrocytes proliferate and therefore the production of matrix molecules at the area of the lesion increases, however, the new matrix is not able to restore the native surface [3].

 When the lesion reaches the subchondral bone (full-thickness lesions), the entry of pluripotent medullary elements is observed [20]. These migratory mesenchymal stem cells produce type I collagen fibers to fill the full thickness defect with fibrocartilage. It should be noted that fibrocartilage is not capable of supplying the damping functions of articular cartilage [21].

Following this line of argumentation, the strategies designed for the treatment of articular cartilage lesions can classically be classified as discussed below.

Palliative as physiotherapy and systemic medications to relieve pain; reparative procedures such as debridement, washing of the knee and ankle joint, arthroscopic arthroplasty, microfracture, and bone marrow stimulation techniques; restorative such as high tibial osteotomy, unicompartmental knee arthroplasty and total knee arthroplasty; and transplantation such as osteochondral transplantation (osteochondral graft), osteochondral autologous transplantation (OATS), and transplantation of a autologous chondrocyte implantation (ACI) [22, 23].

#### **4.1 Microfracture**

Classified within the reparative procedures is the microfracture. Microfracture was introduced into the clinic after other techniques of bone marrow stimulation were used in the late 1980s and early 1990s to penetrate the subchondral bone. This technique improves the migration of MSCs from the bone marrow to the site of the cartilage defect; however, microfracture often results in the formation of fibrocartilage that is biochemically and biomechanically inferior to hyaline articular cartilage [24]. A case series study has shown that without the mechanical robustness of the hyaline tissue, the repair tissue is vulnerable to joint mechanical forces and typically deteriorates between 18 and 24 months after surgery. Such deterioration is particularly evident when treating large defects or those located in the patellofemoral joint [25].

Although the FDA and many physicians still consider microfracture to be the gold standard for cartilage repair, prospective comparative studies show that microfracture could delay cartilage degeneration only in the short term; more than 5 years after surgery, treatment failure can be expected regardless of the size of the lesion [26].

#### **4.2 Osteochondral autologous transplantation (OATS)**

Osteochondral autologous transplantation has been indicated majorly for small-to-medium size (diameter > 10 mm) focal articular cartilage or osteochondral defects of the weigh-bearing areas of the femoral condyles, patellofemoral joint and talus without an acceptable outcome after less invasive techniques [27].

In OATS, a single or multiple osteochondral grafts are harvested from either the less-weight-bearing parts of the femoral condyle or the costal-osteochondral junction. This surgical procedure has the advantage of transplanting viable hyaline cartilage and subchondral bone, which is then transplanted into the defect area to restore the integrity of the articular surface [28].

The disadvantages are basically two: the availability of the grafts and the morbidity of the donor site. The major disadvantage of this procedure is the need to harvest one or multiple grafts from an asymptomatic knee or the rib area. Osteochondral harvesting in OATS often results in considerable donor-site morbidity, showing rates of 17 and 6% for ankle and knee mosaicplasty procedures, respectively, without any significant correlation between the rate of donor-site morbidity and size of the defect, number, and size of the plugs [29]. Furthermore, there is limited evidence on the short- and long-term consequences from harvesting bone plugs of asymptomatic joints.
