Cartilage Regeneration: An Overview

1. Overview
2. Treatment Options
3. Other Considerations
4. Outcome

Overview

In the healthy joint, the ends of the bones meet and are held in proper alignment by a network of muscles, tendons and ligaments. To help them glide smoothly during movement, the ends of the bones are covered with a smooth, glistening substance called articular cartilage.

Unfortunately, disease or injury can damage the cartilage, a development that can cause pain, stiffness, and catching in the joint, and eventually lead to exposure of the underlying bone. This degenerative process is the precursor to arthritis of the joint.

Injuries to the cartilage—which may be referred to as lesions or defects—can occur in any joint, but they are seen most commonly in the knee. This is also the area in which treatment is most commonly attempted because of its accessibility. Among the conditions and diseases that can cause articular cartilage damage are:

• traumatic injury
  
  
• avascular necrosis, in which the bone tissue underlying articular cartilage dies as the result of insufficient blood supply
  
  
• osteochondritis dissecans, in which the blood supply to a discrete area of the bone is disrupted, and which can lead to the breaking off of fragments of bone and cartilage
  
  
• degenerative disease, such as osteoarthritis
  
  
• inflammatory disease, such as rheumatoid arthritis

The diffuse articular cartilage damage of degenerative or inflammatory arthritis is not amenable to cartilage repair procedures. But for localized lesions caused by trauma or other disease, a number of treatment options are available to regenerate cartilage in the injured area.

"Our primary treatment goal is symptom relief," according to Thomas Wickiewicz, MD, Chief, Sports Medicine and Shoulder Service. "Unfortunately, we’re not sure if any of the methods that alleviate pain and stiffness will also produce cartilage that is durable over the course of many years." Instead of having the same smooth, almost transparent texture as the original articular cartilage (also referred to as hyaline cartilage), after injury, the body tends to produce fibrocartilage, a substance that may fill the defect, but may not be able to withstand the stresses the body places on it day after day.

Moreover, no one technique is suitable for every patient or every cartilage defect. Before initiating treatment, the orthopaedic surgeon obtains a high-resolution MRI to assess the problematic area, and then bases his or her recommendation on the size of the defect, the location of the defect and the overall condition of the joint, including the presence of other disease or injury. Surprisingly, while cartilage lesions can cause considerable discomfort, there are many patients who are asymptomatic and whose cartilage lesions are found when their knees are evaluated for another orthopaedic condition, such as an injury to the anterior cruciate ligament (ACL.)

Treatment Options

TREATMENT OPTIONS CURRENTLY IN USE IN THE UNITED STATES INCLUDE:

Debridement or abrasion

Many orthopaedic surgeons choose this technique first for their patients with cartilage injuries. Using arthroscopy—a technique in which a combination of fiber optics, small incisions, and small instruments are used—the surgeon "cleans up" any loose cartilage at the site of the injury. In doing so, bleeding is induced at the bone surface, a process that leads to the growth of fibrocartilage as the body attempts to "repair" itself. The procedure is relatively brief and the patient need not be hospitalized.

A cartilage injury on a patient’s tibial plateau.

The process of debridement

Bleeding on the exposed bone

However, this technique is not successful in every patient, since the fibrocartilage that grows into the gap may not fully fill the defect and may not be durable.

Microfracture

As in the case of debridement, the purpose of microfracture is to provoke a bleeding response and subsequent growth of fibrocartilage. However, with this technique, the surgeon clears away the affected area, and then uses a small surgical instrument to make multiple perforations in the bone.

Area of cartilage loss down to bone

Perforated bone and resultant bleeding

The theory underlying this technique is that bone marrow contains pluripotential cells (similar to embryonic cells in that they are thought to have the capability of acting in one of several different ways) that will differentiate into cartilage in this setting under the influence of motion. Following the procedure, patients use a continuous passive motion (CPM) machine for several hours a day (CPM machines produce movement in the joint during the period in which the patient must avoid putting any weight on the affected area.)

As with all regeneration techniques, the durability of the new cartilage tissue produced with microfracture is in question. However, at least one study showed that in 266 patients followed for a mean of 3.7 years, 75% continued to have overall pain relief; 77% of patients were able to return to sports with an equal or superior performance level as they had pre-injury.

Like debridement, microfracture is a relatively simple and cost-effective procedure that can be performed using arthroscopy. It appears to work best for well-contained lesions. However, in order for the technique to succeed, the patient must avoid any weight-bearing activity on the affected site, necessitating the use crutches for a period of 6-8 weeks. As with debridement, the extent to which the new fibrocartilage fills the defect is unpredictable.

Mosaicplasty or Osteochondral Autograft Transplantation Surgery (OATS)

In this technique, the surgeon removes a dowel of bone (with its cartilage covering) from a healthy area of the joint and transplants it to the area of the defect. The transplanted bone and cartilage is taken from a site where little weight bearing or contact occurs, and the cartilage is less crucial to function. Mosaicplasty may be done with a single plug or with multiple plugs of tissue, And depending on the size and location of the lesion may be done arthroscopicaly or as an open procedure.

Before plug placement

After plug placement

After plug placement

Periosteal Flap

In this surgery, which requires a conventional, open incision, the surgeon removes a piece of the periosteum (a connective tissue that covers all bones) from a low-contact area on the shin, and transplants it to the site of the defect. The periosteum is also thought to contain pluripotential cells that will lead to the regeneration of cartilage. Results with this technique have been mixed. Biopsy studies of the new tissue describe normal-looking cartilage (i.e. having the appearance of articular or hyaline cartilage) mixed with more fibrous patches. Periosteal flap surgery requires an overnight hospital stay.

Autologous Chondrocyte Implantation (ACI)

In this procedure, the orthopaedic surgeon uses arthroscopy to remove a small piece of cartilage from the patient’s knee. (As in mosaicplasty, the cartilage is taken from a relatively low-contact area of the bone.) This tissue is then sent to a laboratory to be cultured and grown into a solution of the patient’s own cartilage cells. With a second procedure, the surgeon then implants the laboratory-grown cells into the knee cartilage defect, using a periosteal patch (from the periosteum) to help the cells adhere and fill in the defect.

ACI can produce good alleviation of symptoms, but it is important to restore the area of the defect to its former dimensions. If the patch is proud (or rises above the rest of the bone surface), it will bear more load than it should during movement. If the patch is recessed, from a biomechanical perspective, it is no different from having a large hole or defect, and weight-bearing load continues to be concentrated on the surrounding cartilage.

This technique requires two operations (one arthroscopic and one open). The periosteal patch may hypertrophy (a phenomenon in which there is an overgrowth of cells) or fall off—developments that make additional surgery necessary. Researchers are currently looking for another method for holding the cartilage cells in place. ACI requires an overnight hospital stay for the second stage of the procedure.

Osteochondral Allografts

In this procedure, the surgeon uses donor tissue to repair the defect. Because donated bone can produce an immunologic response—in which the body reacts negatively to the presence of a foreign tissue—this method is generally more effective for small areas. (The bigger the graft, the greater the potential for a problematic response.) It is also generally more successful in patients who are younger than 45 years old and who have stable joints that are in correct mechanical alignment.

Other Considerations

As noted, the site of the cartilage damage or injury helps dictate the type of procedure the orthopaedic surgeon uses. In the case of the knee, the area is further broken down by compartment. For example in the patello-femoral compartment, for lesions in the trochlea or track for the kneecap, debridement and abrasion often yield good results, especially if there is enough healthy tissue surrounding the area of regeneration to bear the load on the joint and allow new cartilage to mature. Lesions of the femoral condyles, in the medial and lateral compartments, with a large border of normal cartilage will also respond well to this technique. Other areas, such as the patella (the kneecap), are particularly problematic since they are subject to significant shear forces that may damage regenerating tissue.

Patella, Trochlea and Femoral Condyle

Outcome

Unlike many orthopaedic procedures, those done to promote cartilage regeneration have mixed results. And, it’s important to have reasonable expectations, cautions Dr. Wickiewicz. Overall, the bigger and broader the lesion, the more load goes across it, and the less favorable the treatment outcome. Thus, smaller lesions usually respond better to treatment. However, there are some instances in which the surgeon will attempt to repair a large lesion, as in osteochondritis dissecans. Treatment for this condition might include an OATS procedure with instrumentation to hold the plugs in place. The surgery is usually more successful in young people than in older patients.

"A lot of questions about what works best for the short-, intermediate-, and long-term, remain," according to Dr. Wickiewicz. "We need randomized clinical trials on the various techniques for cartilage regeneration to find the answers. And to learn which procedures will not only alleviate symptoms, but provide a durable, long-lasting substitute for the cartilage that has been lost or damaged." Moreover, future developments in the field must take into account that many of the people who require treatment have other problems in the joints, such as mal-alignments or deformities that must be addressed.

The orthopaedic surgeons at the Hospital for Special Surgery (HSS) have performed thousands of cartilage regeneration procedures and continue to study new techniques. An ongoing prospective study at HSS of patients requiring regenerative procedures for articular cartilage injury has resulted in numerous scientific publications and presentations comparing the results of these techniques. One of the goals of this registry is to help HSS surgeons determine which technique is best for a specific lesion, so that for each patient, based on the size and location of the defect, the surgeon may choose the procedure which offers the best possible outcome for that patient.