• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of bmjLink to Publisher's site
BMJ. Jun 10, 2000; 320(7249): 1585–1588.
PMCID: PMC1127369
Science, medicine, and the future

Treating joint damage in young people

George Bentley, professor of orthopaedic surgerya and Tom Minas, clinical instructor in orthopaedic surgeryb

Nearly a quarter of all severe ligament or capsular knee injuries that result in a haemarthrosis are associated with cartilage damage.1,2 Breakdown of the cartilage from trauma or disease results in severe pain and disability and may progress to early osteoarthritis. In young patients this cannot be treated by joint replacement because of the risks of early loosening and “wearing out” of the prosthesis after about 10 years. This article details some of the new techniques that are being developed to restore painless joint function and possibly prevent osteoarthritis.

Methods

Our review is based on our personal experience of laboratory and clinical methods of repair of articular cartilage and a review of relevant current literature. We also included studies assessing outcome, the economics of surgery, and patients' quality of life and data from the proceedings of specialist societies.

Cartilage structure

The articular cartilage that lines joints is tough and resilient. It is essentially composed of a type II collagen sponge supported by water held in place by proteoglycans produced by the chondrocytes embedded in the matrix. The collagen fibres are firmly embedded in the subchondral bone, giving stability to the cartilage. The fibres are arranged as overlapping leaves arising from the subchondral bone that rise to the surface and then bend over to form arches. The proteoglycans and cells are embedded within the collagen fibres (fig (fig1).1).

Figure 1
Spatial relations of collagen, proteoglycans, and cells in cartilage

Proteoglycans are long chain polysaccharides linked to hyaluronate that are negatively charged and hold water within the cartilage by osmotic pressure, thus maintaining the tension of the collagen mesh. However, if the proteoglycans are damaged by trauma or by other agents such as enzymes in inflammatory disease or infection then the proteoglycan structure disintegrates and the water holding capacity is lost, and progressive breakdown of the collagen meshwork then occurs. This leads to exposure of the bone beneath, causing severe pain and disability.

The fundamental problem with cartilage is that it has no nerve supply and is therefore not sensitive to early injuries. It also has poor repair properties, because there are relatively few cells in the tissue, the metabolic rate is low, and the capacity of chondrocytes to divide and migrate in the articular cartilage is restricted by the matrix fibres. As a consequence, it is generally agreed that articular cartilage does not repair significantly after injury to the collagen mesh.

Predicted developments

  • Clarification, by controlled prospective clinical trials, of the precise role of the different repair techniques for different cartilage lesions
  • Early non-invasive diagnosis and monitoring of cartilage damage by magnetic resonance imaging of “at risk” groups
  • Early prophylaxis of cartilage damage and therefore of osteoarthritis by use of growth factors to stimulate repair of cartilage in situ
  • Production of large numbers of human chondrocytes by use of bioreactors and growth of cells in biodegradable matrices could provide customised implants for individual patients
  • Developments for treating knee joints will have application to other joints

Methods of repairing articular cartilage

At present, the clinical applications for cartilage repair are predominantly in patients under 40 years old with painful conditions, including those below, that can lead to early osteoarthritis.

  • Previous ligament and meniscal injuries of the knee followed by persistent pain3
  • Osteochondral fractures after sports injuries—these may be isolated or occur in conjunction with ligament or meniscus injury4
  • Chondromalacia patellae—a poorly understood but common condition of adolescence associated with persistent anterior knee pain and breakdown of the articular cartilage of the patella, which can be recognised only by arthroscopy5
  • Osteochondritis dissecans—a rare condition of teenagers and young adults in which fragments of cartilage and bone separate from the surface of the joint and give rise to loose bodies, producing locking, pain, and swelling6
  • Early osteoarthritis secondary to the above conditions.

Until recently, the only methods of repair of such surface damage to a joint have been by procedures such as drilling or microfracture of the subchondral bone or abrasion arthroplasty.7 All these procedures aim to create bleeding in the joint that will produce a clot on the surface of the exposed bone. Under the stimulus of movement and load bearing, the clot will undergo metaplasia to fibrocartilage, the cells being derived from the bone marrow. However, this cartilage is deficient in type II collagen and normal proteoglycans and therefore functions for only a limited period.

Cartilage transplantation

Over the past 100 years attempts have been made to repair damaged articular cartilage by allografts. The most important of these is cartilage transplantation. Cartilage can be transplanted in one of three forms:

  • Osteochondral grafts that include a shell of cartilage and its subchondral bone cut to size to fill the defect
  • Intact cartilage grafts without their subchondral bone, glued to the damaged area
  • Chondrocytes, either isolated or isolated and cultured.

Osteochondral allografts

Osteochondral allografts can be extremely successful, but there are relatively few centres in Britain that use this technique, and cartilage cannot be harvested at routine orthopaedic operations because in such operations the joint is usually damaged, rendering the cartilage unsuitable. Since living grafts are used from renal transplant donors there is a small risk of transmission of infection such as HIV and hepatitis. In recent experiments human cartilage has been stored for up to three months to establish the disease status of the donor and hence the potential risk to a recipient of the cartilage graft.8 The structure of the stored cartilage could be maintained both biochemically and mechanically. This method offers great promise for the future repair of large cartilage and bony defects such as those resulting from major road accidents, and it holds out the possibility of banking of grafts for longer periods.

Isolated chondrocyte allografts

Autologous chondrocyte grafting was developed by Brittberg and colleagues in Gothenburg.9 Cartilage from the margins of the knee joint is harvested by arthroscopy, and the cells are cultured for four weeks, after which they are transplanted into the damaged area (fig (fig2).2). The cells are held in position by a membrane of periosteum taken from the upper tibia which is sutured into position over the cartilage defect before injection of cells. At present, this is done by open operation, and the rehabilitation period is eight weeks before return to normal activities and one year before returning to sport. The latest results of this method in 102 patients are encouraging.10 Furthermore, these authors showed that there was a correlation between the quality of the biopsy material and the clinical results over a period now extending for four years.

Figure 2
Autologous chondrocyte grafting. Cartilage is removed from margins of patient's knee, and cartilage cells are cultured for 4-6 weeks. They are then injected into the damaged area beneath a membrane of periosteum secured by sutures. (Adapted from Brittberg ...

In a separate study the efficacy of autologous chondrocyte transplantation and the impact on quality of life was studied in 59 patients with cartilage defects after trauma.11,12 Quality of life was significantly enhanced 12 months after implantation, and the estimated cost per additional quality adjusted life year was $6791. This is better than that reported in separate studies for total knee replacement arthroplasty and lumbar discectomy, which are generally accepted as successful procedures.

There are, however, several problems which limit the efficacy of this technique:

  • The cells may not survive and multiply in culture
  • The cartilage cells in culture may undergo dedifferentiation to fibroblasts13
  • The fate of the implanted cells is uncertain
  • It is not known whether the periosteal covering provides growth factors or cells that contribute to the repair or whether it is simply a retaining membrane for the cells.14

Mosaicplasty

Mosaicplasty differs from articular cartilage transplantation in that it involves harvesting plugs of cartilage from the margins of the knee joint and the intercondylar notch and transplanting these directly into the defect in the articular surface rather than isolating the cartilage cells and growing them in culture before implantation (fig (fig3).3). This method has attractions in that it is carried out in one procedure and can be performed through a small incision. Hangody has reported similar results to those achieved by autologous chondrocyte transplantation, with 90% success with cartilage defects on the femoral condyles and 60% on the patella over three years in 57 patients.15

Figure 3
Mosaicplasty, in which osteochondral plugs are removed from the non-articular margins of the knee and transplanted into the cartilage defect on the femoral condyle in the form of a mosaic

This method also has drawbacks, however:

  • Incomplete filling of the defect because of insufficient supply of graft, since only a certain amount can be removed from the undamaged area of the joint
  • The possibility of morbidity at the donor site from removal of the cartilage plugs leading to osteoarthritis.

A prospective randomised controlled clinical trial is in progress to compare mosaicplasty and autologous chondrocyte transplantation in patients with articular cartilage defects of the knee from acute osteochondral fractures, osteochondritis dissecans, and chondromalacia patellae.

Carbon fibre matrix support prosthesis

The carbon fibre matrix support prosthesis is based on the principle that a pad of fibres of pure carbon 7 μm in diameter is inserted through a 5 cm long incision into the subchondral bone of the knee below an articular cartilage defect. The carbon mesh will support the blood clot and fibrocartilage that is formed as a natural healing response by the subchondral bone. This will give a much firmer fibrocartilage surface than that produced by traditional procedures such as drilling, abrasion arthroplasty, or microfracture and therefore should give better pain relief and surface repair. The technique involves removing 2-3 mm of subchondral bone in the defect and then “press fitting” the carbon fibre mesh into it.

This method clearly does not replace the articular cartilage with normal cartilage but provides a protective pad of fibrocartilage which seems to last for up to six years, and it is interesting that the results are similar to those for the other cartilage transplantation methods.16,17

Both mosaicplasty and the carbon fibre matrix support prosthesis technique involve an open procedure, which means that patients will take four to six weeks to recover. Also, because repair in the articular surface is expected to proceed only slowly, it is necessary to avoid running and sport for 12 months after the operation.

Future developments in cartilage repair

The way forward in cartilage repair is likely to be based on cultured cells supported in engineered tissue. A variety of cells will grow in an artificial matrix, and exciting work is going on in developing different biodegradable matrices that could support cartilage growth for some months while the cartilage cells and matrix become established. The principle is to grow the cells throughout the matrix and to implant both together into an articular defect. The matrix will then gradually degrade over 8-10 weeks. Several matrices have been tested, such as collagen type I and alginate.

A further development is to massively increase the numbers of cells produced in culture by using bioreactors, which are mechanical devices that cause controlled movement of cells during culture and thus improve the entry of nutrients and allow more rapid proliferation. This method has been developed in the laboratory with human articular cartilage cells and the results indicate how the cell numbers can be greatly increased. Also the penetration of the cells into the matrices is improved by the use of bioreactors (fig (fig4).4). The combination of these methods of cell culture with the use of growth factors such as transforming growth factor β allows much greater yields of cells from small biopsies, which would reduce the risk of joint damage from harvesting.

Figure 4
Human chondrocytes grown in alginate biodegradable matrix for 14 days in a static culture system (upper images) and bioreactor (lower images). More abundant histochemical staining in cultures in bioreactor, both at edge of matrix (left) and at centre ...

An alternative source of cartilage cells in the future may well be human stem cells taken from the bone marrow of the patient, which could be modified by culture conditions to produce cartilage cells and matrix.18 This method has the theoretical advantage of providing unlimited numbers of cells and thus would avoid the need to harvest from the patient's joint, reducing the surgery required and the possible damage produced by harvesting. Xenografts derived from animal sources might also be used and could be stored in tissue banks for use when required.

Conclusions

Early diagnosis of cartilage damage may be achieved in future by magnetic resonance imaging of “at risk” groups and by genetic screening as the techniques improve.19,20 This would make patient selection possible and allow monitoring of cartilage healing without arthroscopy.

Early prophylaxis of cartilage damage and therefore of osteoarthritis might well be achieved by the use of growth factors to stimulate repair of cartilage in situ before breakdown of the collagen mesh. With more advanced damage, the production of large numbers of human chondrocytes by the use of bioreactors and the growth of cells in biodegradable matrices could lead to customised implants for individual patients and cartilage defects.

Developments in treatment of the knee joint will have application in future to other joints with cartilage damage such as the hip, ankle, shoulder, spine, and hands, potentially greatly reducing the prevalence of established osteoarthritis.

Footnotes

 Competing interests: None declared.

References

1. Curl WW, Krome J, Gordon S, Rushing J, Smith BP, Poehling GG. Cartilage injuries: a review of 31,516 knee arthroscopies. Arthroscopy. 1997;13:456–460. [PubMed]
2. Sandberg R, Balkfors B, Henricson A, Westlin N. Traumatic hemarthrosis in stable knees. Acta Orthop Scand. 1986;57:516–517. [PubMed]
3. Maffulli N, Binfield PM, King JB, Good CJ. Acute haemarthrosis of the knee in athletes. J Bone Joint Surg. 1993;75B:945–949. [PubMed]
4. Zamber RW, Teitz CC, McGuire DA, Frost JD, Hermanson BK. Articular cartilage lesions of the knee. Arthroscopy. 1989;5:258–268. [PubMed]
5. Bentley G. The surgical treatment of chondromalacia patellae. J Bone Joint Surg. 1978;60B:74–81. [PubMed]
6. Twyman RS, Desai K, Aichroth PM. Osteochondritis dissecans of the knee: a long-term study. J Bone Joint Surg. 1991;73B:461–464. [PubMed]
7. Buckwater JA. Evaluating methods of restoring cartilaginous articular surfaces. Clin Orthop. 1999;S244:238. [PubMed]
8. White AE, Bentley G, Stephens MD, Bader DL, Giddins GE, Lee DA. The effects of storage temperature on the composition, metabolism and biomechanical properties of human articular cartilage. In:. The knee. Amsterdam: Elsevier Science (in press).
9. Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med. 1994;331:889. [PubMed]
10. Peterson L, Minas T, Brittberg M, Nilsson A, Sjogren-Jansson E, Lindahl A. The long term outcome of autologous chondrocyte transplantation for full thickness chondral defects of the knee. In: Cartilage regeneration and repair, where are we? Proceedings of International Cartilage Repair Society, 2nd symposium, Boston, USA, 16-19th November 1998. www.mgh.harvard.edu/depts/hoj/html/cartilage_repair.html (accessed 2 June 2000).
11. Minas T. Chondrocyte implantation in the repair of chondral lesions of the knee: economics and quality of life. Am J Orthop. 1998;11:739–744. [PubMed]
12. Minas T. Clinical outcomes after autologous chondrocyte implantation. In: American Academy of Orthopaedic Surgeons, 66th annual meeting, Anaheim, California, USA, February 4th-8th 1999. www.aaos.org/wordhtml/meet99.htm (accessed 2 June 2000).
13. Binette F, McQuaid DP, Haudenschild DR, Yaeger PC, McPherson J, Tubo R. Expression of stable articular cartilage phenotype without evidence of hypertrophy by adult human articular chondrocytes in vitro. J Orthop Res. 1998;16:207–216. [PubMed]
14. Breinan HA, Minas T, Barone L, Tubo R, Hsu HP, Shortkroff S, et al. Histological evaluation of the course of healing of canine articular cartilage defects treated with cultured autologous chondrocytes. Tissue Eng. 1998;4:101–113.
15. Hangody L, Kish G, Karpati Z. Mosaicplasty for the treatment of articular cartilage defects: application in clinical practice. Orthopaedics. 1998;21:751–756. [PubMed]
16. Meister K, Cobb AG, Bentley G. Treatment of painful articular cartilage defects of the patella by carbon fibre implants. J Bone Joint Surg. 1998;80B:965. [PubMed]
17. Bentley G, Norman D, Haddad FS. An 8 year experience of cartilage repair by matrix support prosthesis. Proceedings of International Cartilage Repair Society, 2nd symposium, Boston, USA, 16-19th November 1998. J Sports Med (in press).
18. Wakitani S, Goto T, Pineda S, Young R, Mansour J, Caplan A, et al. Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg. 1994;76A:579–592. [PubMed]
19. Johnstone B, Hering T, Caplan A, Goldberg V, Yoo J. In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res. 1998;238:265–272. [PubMed]
20. Disler DG, McCauley TR, Kelman CG, Fuchs MD, Ratner LM, Wirth CR, et al. Fat-suppressed three-dimensional spoiled gradient-echo MR imaging of hyaline cartilage defects in the knee; comparison with standard MR imaging and arthroscopy. Am J Roentgenology. 1996;167:127–132. [PubMed]

Articles from BMJ : British Medical Journal are provided here courtesy of BMJ Group
PubReader format: click here to try

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • PubMed
    PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...