Knee cartilage replacement therapy

Articular cartilage, most notably that which is found in the knee joint, is generally characterized by very low friction, high wear resistance, and poor regenerative qualities. It is responsible for much of the compressive resistance and load bearing qualities of the knee joint and, without it, walking is painful to impossible. Osteoarthritis is a common condition of cartilage failure that can lead to limited range of motion, bone damage and invariably, pain. Due to a combination of acute stress and chronic fatigue, osteoarthritis directly manifests itself in a wearing away of the articular surface and, in extreme cases, bone can be exposed in the joint. Some additional examples of cartilage failure mechanisms include cellular matrix linkage rupture, chondrocyte protein synthesis inhibition, and chondrocyte apoptosis. There are several different repair options available for cartilage damage or failure.

Non-surgical treatments

Osteoarthritis is the second leading cause of disability in the elderly population in the United States. It is a degenerative disorder that generally starts off relatively mild and escalates with time and wear. For those patients experiencing mild to moderate symptoms, the disorder can be dealt with by several non-surgical treatments. The use of braces and drug therapies, such as anti-inflammatories (ex. diclofenac, ibuprofen, and naproxen), COX-2 selective inhibitors, hydrocortisone,have been shown to alleviate the pain caused by cartilage deficiency.

Non-biological treatments

This type of repair, short of total joint replacement, can be divided into three groups.

Chondrectomy and debridement

Treatments that remove the diseased and undermined cartilage with an aim to stop inflammation and pain include shaving (chondrectomy) and debridement.

It is interesting to note that debridement, introduced by Magnuson in 1941, does not have any scientific basis for existence; in fact, it is deleterious in terms of knee biomechanics. It is used palliatively as it temporarily relieves pain associated with arthritic inflammation. Many insurance companies (ex. Aetna) consider the procedure experimental because there is no evidence proving its effectiveness.

Abrasion and microfracture surgery

Another group of treatments consists of a range of abrasive procedures aimed at triggering cartilage production, such as drilling, microfracture surgery, chondroplasty, and spongialization.

Abrasion, drilling, and microfracture originated 20 years ago. They rely on the phenomenon of spontaneous repair of the cartilage tissue following vascular injury to the subchondral bone.

Laser-assisted treatments

Laser assisted treatments, currently experimental, compose a third category; they combine the removal of diseased cartilage with cartilage reshaping and also induce cartilage proliferation.

Laser abrasion provides gentle cutting of the cartilage. It uses heat to induce alterations in the physical matrix, which results in shape change and stress reduction. Improving this therapy to make it more spatially selective would avoid excessive tissue damage such as air bubble formation, tissue necrosis, reactive synovitis, chondrolysis, and an acceleration of articular cartilage degeneration.

Autologous matrix-induced chondrogenesis

Autologous matrix-induced chondrogenesis, which is also known as AMIC, is a biological treatment option for articular cartilage damage bone marrow stimulating technique in combination with a collagen membrane. It is based on the microfracture surgery with the application of a bi-layer collagen I/III membrane.

The AMIC technique was developed to improve some of the shortfalls of microfracture surgery such as variable repair cartilage volume and functional deterioration over time. The collagen membrane protects and stabilizes the MSCs released through microfracture and enhances their chondrogenic differentiation.

The AMIC surgery is a single-step procedure. Once cartilage damage is assessed there are two methods to access the joint to proceed with the AMIC surgery. First is to perform a mini arthrotomy. Second is an all-arthroscopic procedure.[1]

Autologous chondrocyte implantation

The human body's own cartilage is still the best material for lining knee joints. This drives efforts to develop ways of using a person's own cells to grow, or re-grow cartilage tissue to replace missing or damaged cartilage. One cell-based replacement technique is called autologous chondrocyte implantation (ACI) or autologous chondrocyte transplantation (ACT).

A review evaluating autologous chondrocyte implantation was published in 2010. The conclusions are that it is an effective treatment for full thickness chondral defects. The evidence does not suggest ACI is superior to other treatments.[2]

One ACI treatment, called Carticel, is designated for young, healthy patients with medium to large sized damage to cartilage and is not applicable to osteoarthritis patients. The patient’s chondrocytes are removed arthroscopically from a non load-bearing area from either the intercondylar notch or the superior ridge of the medial or lateral femoral condyles. 10,000 cells are harvested and grown in vitro for approximately six weeks until the population reaches 10-12 million cells. Then these cells are injected into the patient. These cells are held in place by a small piece of soft tissue from the tibia, called a periosteal flap, which is sutured over the area to serve as a watertight lid. The implanted chondrocytes then divide and integrate with surrounding tissue and potentially generate hyaline-like cartilage. The cost of the treatment ranges from ($USD) 20,000-35,000. A second generation technique, called Carticel II uses a "fleece matrix" implanted with chondrocyte cells that is arthroscopically inserted into the joint. This procedure is known as matrix autologous chondrocyte implantation or (MACI) and is available in Germany, UK, and Australia.[3]

A variation on the Carticel technique, called matrix-associated autologous chondrocyte transplantation (MACT), grows the patient's cells in a 3D matrix of resorbable tissue which is implanted via an open or arthroscopic procedure. It appears to be a simpler technique and resolves some of the issues of using Carticel under a periosteal patch.[4]

Another ACI technique, using "chrondospheres", uses only chrondrocytes and no matrix material. The cells grow in self-organized spheroid matrices which are implanted via injected fluid or inserted tissue matrix.[5]

Autologous mesenchymal stem cell transplantation

For years, the concept of harvesting stem cells and re-implanting them into one's own body to regenerate organs and tissues has been embraced and researched in animal models. In particular, mesenchymal stem cells have been shown in animal models to regenerate cartilage.[6] Recently, there have been several published case reports of successful cartilage growth in human knees using autologous cultured mesenchymal stem cells.[7] In addition, an n=229 safety study has also been published showing safety better than surgical alternatives for this cultured cell injection procedure at a 3-year follow-up.[8] An advantage to this approach is that a person's own stem cells are used, avoiding transmission of genetic diseases.

Microdrilling augmented with peripheral blood stem cells

A 2011 study reports histologically confirmed hyaline cartilage regrowth in a 5 patient case-series, 2 with grade IV bipolar or kissing lesions in the knee. The successful protocol involves arthroscopic microdrilling/ microfracture surgery followed by postoperative injections of autologous peripheral blood progenitor cells(PBPC's) and hyaluronic acid(HA).[9] PBPC’s are a blood product containing mesenchymal stem cells and is obtained by mobilizing the stem cells into the peripheral blood. Dr. Khay Yong Saw and his team propose that the microdrilling surgery creates a blood clot scaffold on which injected PBPC’s can be recruited and enhance chondrogenesis at the site of the contained lesion. They explain that the significance of this cartilage regeneration protocol is that it is successful in patients with historically difficult-to-treat grade IV bipolar or bone-on-bone osteochondral lesions.

Dr. Saw and his team are currently conducting a larger randomized trial and working towards beginning a multicenter study. The work of the Malaysian research team is gaining international attention.[10]

Osteochondral autograft

Osteochondral autograft (OATS) is a technique that requires that the surgeon transplant sections of bone and cartilage. First, the damaged section of bone and cartilage is removed from the joint. Then a new healthy dowel of bone with its cartilage covering is removed from the same joint and transplanted or grafted into the hole left from removing the old damaged bone and cartilage. The healthy bone and cartilage are taken from areas of low stress in the joint so as to prevent weakening the joint. Depending on the severity and overall size of the damage multiple plugs or dowels may be required to adequately repair the joint. A similar treatment, known as mosaicplasty, is described in the next paragraph.

Grafting

There are three methods of grafting cartilage defects, including periosteal grafting, osteochondral grafting (mosaicplasty), and articular cartilage stem cell paste grafting. Periosteal grafts are harvested from the perichondrial tissue and grafted to the articular cartilage defect. Given low long-term success rates, perichondrial grafting alone has not been clinically accepted as a particularly excellent therapy. Mosaicplasty, a form of chondral grafting, is a therapy designed to replace cartilage on the surface of the knee joint that has been damaged by trauma or arthritis by implanting osteochondral plugs. The implants can be autogenic (autologous) or allogenic. Paste grafting involves replacing damaged cartilage with autologous cartilage and cancellous bone from the intercondylar notch in the center of the knee that is first morselized into a paste (typically with hydroxyapatite) to better fill the defect and more successfully promote chondrocyte activity and cartilage formation. These procedures are often performed arthroscopically.

Joint replacement

Total knee replacement is reserved for the most severe and recalcitrant forms of osteoarthritis. When other forms of treatment fail or when patients are unlikely to succeed with lesser therapies, the last option to treat defective cartilage is to replace all or part of the joint. In knee joint replacement, the worn out surfaces of the knee are resurfaced with metal and plastic, replacing the poorly functioning natural joint with new surfaces that slide together smoothly. The dysfunctional joint is removed and pain is relieved. Total knee replacement is considered a relatively routine surgery with outcome from surgery indicating 85% of patients are happy with the procedure, approximately 10% do not see a significant improvement and 5% report worsening of symptoms. There are more than 300,000 total knee replacements in the United States each year. The average patient age is between 65 and 75. Of these surgeries, approximately 80% are unilateral (only one knee replaced) and 20% are bilateral. Women undergo the procedure more often than men, making up 60% of the patient population.

See also

External links

References

  1. ↑ Piontek, Tomasz; Ciemniewska-Gorzela Kinga; Szulc Andrzej; Naczk Jakub; Słomczykowski Michał (30 August 2011). "All-arthroscopic AMIC procedure for repair of cartilage defects of the knee". Knee Surgery, Sports Traumatology, Arthroscopy: 1–4. doi:10.1007/s00167-011-1657-z. ISSN 0942-2056.
  2. ↑ Vasiliadis, H.; Wasiak, J.; Salanti, G. (2010). "Autologous chondrocyte implantation for the treatment of cartilage lesions of the knee: a systematic review of randomized studies". Knee Surgery, Sports Traumatology, Arthroscopy 18 (12): 1645–1655. doi:10.1007/s00167-010-1050-3. PMID 20127071.
  3. ↑ Carticel developed by Genzyme Corporation
  4. ↑ 3D MACT developed by BioTissue Technologies GmbH
  5. ↑ Thermann, H; Driessen, A; Becher, C (March 2008). "Autologous chondrocyte transplantation in the treatment of articular cartilage lesions of the talus". Orthopade (in German) (nih.gov) 37 (3, number 3): 232–9. doi:10.1007/s00132-008-1215-7. PMID 18317730.
  6. ↑ Yamasaki T, Deie M, Shinomiya R, et al. (October 2005). "Meniscal regeneration using tissue engineering with a scaffold derived from a rat meniscus and mesenchymal stromal cells derived from rat bone marrow". J Biomed Mater Res A 75 (1): 23–30. doi:10.1002/jbm.a.30369. PMID 16049928.
  7. ↑ Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D (2008). "Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells". Pain Physician 11 (3): 343–53. PMID 18523506.
  8. ↑ Centeno CJ, Schultz J, Cheever M, J, Freeman M, Marasco W (2010). "Safety and complications reporting on the re-implantation of culture-expanded mesenchymal stem cells using autologous platelet lysate technique". Current Stem Cell Research and Therapy 5 (1): 81–93. doi:10.2174/157488810790442796. PMID 19951252.
  9. ↑ Saw, KY; Anz A; Merican S; Tay YG; Ragavanaidu K; Jee CS; McGuire DA (April 2011). "Articular cartilage regeneration with autologous peripheral blood progenitor cells and hyaluronic Acid after arthroscopic subchondral drilling: a report of 5 cases with histology". Arthroscopy 27 (4): 493–506. doi:10.1016/j.arthro.2010.11.054. PMID 21334844.
  10. ↑ Wey Wen, Lim. "Generating New Cartilage". The Star. Retrieved 6 May 2011.
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