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Articular Cartilage Damage and Repair |
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"It should be clear that cartilage does not yield its secrets easily and that inducing cartilage to heal is not simple. The tissue is difficult to work with, injuries to joint surface, whether traumatic or degenerative, are unforgiving, and the progression to osteoarthritis is sometimes so slow that we delude ourselves into thinking we are doing better than we are. It is important, however, to keep trying." Dr Henry Mankin, Boston, Massachusetts, USA. What is Articular Cartilage?Articular cartilage is a highly organized avascular tissue composed of chondrocytes embedded within an extracellular matrix of collagens, proteoglycans and noncollagenous proteins. Its primary function is to enable the smooth articulation of joint surfaces, and to cushion compressive, tensile and shearing forces. Hyaline cartilage has one of the lowest coefficients of friction known for any surface to surface contact.
Hyaline articular cartilage provides the bearing surface of synovial joints. Cartilage is unique as it is an avascular, aneural tissue, in which cells survive for a lifetime, without intercellular connections. In particular, adult articular cartilage has no other known function than maintaining mechanical competence. Owing to its sophisticated composition, its high water content and its ability to withstand hydrostatic pressurization, cartilage is capable of transferring enormous forces relatively evenly from one subchondral bone plate to the other. Under physiological conditions, cartilage also provides an almost frictionless gliding surface and is thus capable of transferring these loads during motion. In order to be able to meet these complex mechanical demands without undergoing wear and tear, articular cartilage displays unique morphological and biomechanical properties. These properties are yet unmatched by any artificial material, despite considerable efforts by engineers and biologists. Although hyaline articular cartilage appears to display atrophic changes (thinning) during unloading and may exhibit compositional changes (increase in GAG) after exercise, it seems to differ from other musculoskeletal tissues with load-bearing function as it cannot increase tissue mass postnatally as a result of mechanical stimulation.
Why is articular cartilage repair necessary?Cartilage is frequently injured, often as a result of sports related trauma, but due to its avascular nature, articular cartilage has very limited capacity for repair. Injuries of the articular cartilage that do not penetrate the subchondral bone (partial thickness) do not heal and usually progress to the degeneration of the articular surface. Injuries that penetrate the subchondral bone undergo repair through the formation of fibrocartilage.
Although fibrocartilage fills and covers the defect, this is the right tissue from the biomechanical standpoint. The fibrocartilage is made to resist tension forces, while the hyaline cartilage is made to resist compression forces, to enable smooth articulation, and to withstand long-term variable cyclic load and shearing forces. Focal articular cartilage defects, often found in young adults, have been increasingly recognized as a cause of pain and functional problems. There is more and more clinical evidence that full thickness articular cartilage defects continue to progress and deteriorate, although at a slow rate. Early diagnosis and treatment of these patients is recommended prior to the development of more advanced osteoarthritis. In selecting methods of restoring the damaged articular surface, it is important to distinguish articular cartilage repair from articular cartilage regeneration. Repair refers to the healing of injured tissues or replacement of lost tissues by cell proliferation and synthesis of new extracellular matrix. Unfortunately, repaired articular cartilage generally fails to replicate the structure, composition, and function of normal articular cartilage. Regeneration in this context refers to the formation of an entirely new articulating surface that essentially duplicates the original articular cartilage. Therefore, the best we can do at present is to repair chondral or osteochondral defects with functionally similar tissue. Articular cartilage repair and reconstructive proceduresHistorically there have been many attempts to develop clinically useful procedures to repair damaged articular cartilage. However, most cartilage repair techniques have not proved entirely successful yet. At present, the treatment options are still limited and the long-term outcome is still uncertain. The principal goals for surgical management of the symptomatic chondral and osteochondral defects are to reduce symptoms, improve joint congruence by restoring the joint surface with the best possible tissue, and to prevent additional cartilage deterioration. Although the need for surgical management is based on the patient's history, physical examination, and imaging studies, only knee arthroscopy will provide definitive information regarding the lesion's characteristics (ie, location, size and depth) and associated injuries (menisci and cruciate ligaments). Based upon their anticipated outcome, it is helpful to define treatment options as being palliative, reparative, or restorative. First-line treatment for smaller injuries in lower-demand patients with limited symptoms can be treated effectively with palliative procedures such as Debridement and lavage. Relief, however, may be incomplete and short-lived. Mid-sized lesions in patients with moderate symptoms can be treated with a reparative procedure using a Marrow-stimulating technique (Microfracture) in an effort to promote a fibrocartilage healing response. Results in larger lesions in higher-demand patients, however, are generally less favorable and shorter-lived, independent of any prior treatments rendered. Larger defects, especially in higher-demand patients with significant symptoms who have failed less aggressive primary treatment options, are most effectively treated with a restorative treatment option such as Osteochondral Autologous Graft Transplantation (OATS) and Autologous Chondrocyte Implantation (ACI). See also:Debridement and LavageLavage (arthroscopic washout) is one of the most basic of traditional arthroscopic techniques. Dr Robert Jackson, the pioneer of arthroscopy in North America, observed that in the course of performing diagnostic arthroscopies patients with intra-articular knee problems had significant pain relief following joint lavage. Exactly how arthroscopic lavage and debridement may help the early symptoms of osteoarthritis is still not entirely clear. Joint lavage removes loose intra-articular tissue debris and inflammatory mediators known to be generated by the synovial lining. In early stages, removing these degradative enzymes from the joint may allow chondrocyes to increase their biosynthetic activity. Another mechanism by which lavage may relieve the symptoms and increase the resiliency and stiffness of articular cartilage is through changing the ionic environment within the synovial fluid. Lavage may provide some patients with advanced degenerative disease of the knee, which may last as long as 3 years. However, the lavage provides only short-term symptomatic relief without correction of underlying pathology. If predisposing malalignment is not corrected, the beneficial effects seem to be minimised. The outcome of this simple procedure is generally insufficient for the active population, and benefits are short-lived. MicrofractureThis technique was developed and popularised by Dr Richard Stedman, from Vail, Colorado, USA. The treatment involves a disruption of subchondral bone in an attempt to induce bleeding (fibrin clot formation) and to initiate primitive stem cell migration from the bone marrow into the cartilage defect site.
These techniques utilise primitive stem cells, which are capable of differentiating into bone and cartilage under the influence of various biologic and mechanical intraarticular factors. The subchondral bone is penetrated in order to reach a zone of vascularisation, stimulating the formation of a fibrin clot containing pluripotential stem cells. This clot differentiates and remodels, resulting in a fibrocartilaginous repair tissue. Although fibrocartilage often appears to offer the patient significant pain relief, this tissue lacks several key structural components to perform the mechanical functions, as a wear-resistant and as a weight-bearing surface. The fibrocartilage repair tissue does not produce a proper compressive stiffness against applied mechanical load and thus is subjected to an excessive deformation under physiological loading. This in turn may cause a mechanical failure of the repaired tissue and eventually lead to a recurrence of degeneration of the repaired articulating surface. Further information:
Autologous Matrix Induced Chondrogenesis (AMIC)The AMIC® technique is new biological cartilage repair method. This innovative technique uses the body’s own healing potential and the regenerative capacity of mesenchymal stem cells. It can be applied to full thickness cartilage defects that extend down to the subchondral bone and are bigger than 1 to 2 cm2.The AMIC® technique is based on proven biological concepts first demonstrated by Dr Richard Steadman with his microfracture method. The shortcoming with microfracture is that it only appears to be able to regenerate fibrocartilage and not hyaline cartilage which is much stiffer and more resistant to shear forces. AMIC® differs from microfracture in that a cover, in the form of the Chondro-Gide® collagen matrix, is applied over the defect immediately following microfracture (the subchondral bone plate is penetrated using a sharp awl or microfracture pick approximately 4 to 5 mm apart). The Chondro-Gide®matrix can be fixed with fibrin glue, sutures or resorbable pins. This cover then traps the first few millilitres of bone marrow bleeding which contain the highest percentage of mesenchymal stem cells to form a so called ‘Superclot’. In so doing the first and most important clot is kept in place and not lost into the joint which appears to happen with microfracture. The Chondro-Gide® collagen matrix forms the roof of a ‘biological chamber’ and serves to protect and contain the stem cells as they differentiate into chondrocytes, which will form a healthy regenerative cartilage. Source: Geistlich Surgery. Osteochondral Autologous Transplantation (OATS)
This technique was developed simultaneously by Dr Laszlo Hangody in Hungary (MosaicPlasty) and Mr Vladimir Bobic in the UK (OATS) approximately 14 years ago. Osteochondral autograft transplantation seems to be the only surgical technique that can restore the height and the shape of articulating surface in focal osteochondral defects, with composite autologous material that contains all necessary ingredients: hyaline articular cartilage, intact tidemark and a firm bone carrier. However, like many other orthopaedic procedures that require the use of autologous tissues, osteochondral autograft transfer (or MosaicPlasty) is the "rob Peter to pay Paul" situation. The main problem with this reconstructive technique is the limited availability of autografts, which significantly reduces the choice of treatable defects down to a small focal chondral defect, and a long-term donor morbidity in multiple donor sites. Deep and large, crater-like osteochondral defects are not suitable for osteochondral autograft transplantation, mainly because of the limited availability of autologous osteochondral grafts. Also, it is difficult to reconstruct the subchondral bone and restore the contour of the defect area, and to cover the entire defect area with hyaline articular cartilage. The dead spaces between circular grafts, the lack of integration of donor and recipient hyaline cartilage, different orientation, thickness and mechanical properties of donor and recipient hyaline cartilage are further sources of clinical concern. For more information on Osteochondral Grafting please see the folowing articles:
The longevity of autologous osteochondral transplantation:
Long-term follow-up has shown mosaicplasty to be a successful option for treating full-thickness defects in the knee and other weight-bearing joints. “There were a lot of clinical evaluations of the mosaicplasty technique and many of them published a similar outcome — about a 90% success rate,” László Hangody, MD, PhD, said during his presentation at the 8th World Congress of the International Cartilage Repair Society. Hangody and colleagues, from the Uzsoki Hospital in Budapest, Hungary, in their follow-up of 1,178 mosaicplasties performed in different joints between 1992 and 2007, found good to excellent results with a low complication rate. A subset analysis of 849 femoral condylar cases with 10.3 years follow-up revealed a modified Hospital for Special Surgery (HSS) score of 92 points and a modified Cincinnati Knee Score (CKS) of 89 points. An 8.9 year follow-up of 36 tibial condylar cases showed an HSS score of 87 and a CKS score of 85. In addition, an analysis of 171 patellar and trochlear cases with 9.3 years follow-up showed an HSS score of 79, a CKS score of 72 and a Bandi score of 76%. Using the Bandi score, they also found a long-term donor site morbidity of 3%. Hangody and his colleagues have also found good results using mosaicplasty to treat high-level athletes. “At 10-years follow-up, 64% of our patients returned to the same level of sports activity,” Hangody said. “19% returned to a lower level of sports activity and only 17% were finished in their sports career.” He also noted that the procedure is indicated for patients with symptomatic focal chondral or osteochondral defects measuring between 1 cm2 and 4 cm2.
TruFit CB PlugsTruFit CB Plugs (Smith and Nephew, London, UK), are synthetic cylindrical biphasic absorbable scaffolds, based on PolyGraft Technology, designed to capture and retain bone marrow elements and encourage differentiation into articular cartilage and bone. Three-dimensional porous scaffold with interconnected pores (mean diameter of 250 μm) encourages tissue ingrowth and remodeling. This techinology is approved for use in UK. In the US this product is marketed by Smith & Nephew as TRUFIT BGS Plug, as Bone Graft Substitute for filling circular drill holes in bone, with the following disclaimer: "the safety and effectiveness of this device in osteochondral defects have not been established". This product is not intended for articular cartilage repair in the USA.
The authors conclude that TruFit plugs offer an attractive solution to the management of full thickness chondral injuries enabling rapid mobilisation and return to sport. TruFit plugs provide a stable scaffold for early mobilisation of the knee post operatively, avoiding the prolonged period of limited weight bearing as follows microfracture, and the long recovery time following ACI. They believe that TruFit plugs appear to provide a simple one step solution in the management of small areas of chondral injury (<2cm diameter), particularly in patients who require rapid rehabilitation, and are keen to remain active at a high level.
Autologous Chondrocyte Implantation (ACI)This advanced FDA-approved technology allows cartilage cells, know as chondrocytes, to be harvested from your knee and cultured and multiplied. The fresh chondrocytes are then re-implanted in your knee and cause hyaline-like cartilage to repair the defect in articulating surface.
Our clinical experience with femoral, trochlear and patellar ACI surgery goes back to 1998. We have been using TiGenix ChondroCelect ACI (CCI) technology with Geistlich Chondro-Gide® membrane at Chester Knee Clinic, The Grosvenor Hospital Chester, since November 2004. The ACI restores the articular surface with your own functional repair tissue without compromising the integrity of healthy surrounding cartilage or the subchondral bone. This technology has demonstrated significant benefits in patients with a femoral focal lesion, in terms of diminished pain and improved function. If you have this type of lesion, then ACI may be an appropriate treatment option. The surgical procedure consists of two steps:
The Chondro-Gide® is a CE-marked bilayer collagen matrix which has been especially designed for articular cartilage repair methods. The membrane consists of porcine-origin collagen Type I/III made ACI treatment is particularly suited for larger defects. Suitable patients would be generally young and healthy individuals, who have had an injury to the knee, and a so-called osteochondral lesion, over the past few months or years, and have continued to have pain, swelling and mechanical problems. This is a new procedure (in clinical use since 1987) and although it has been performed on over 30000 patients internationally, especially in Sweden and the USA, not every patient is suitable and not every patient achieves a completely satisfactory functional outcome. The longevity of ACI repair:Long-term follow-up highlights the durability and efficacy of ACI surgerySource: Gina Brockenbrough, 1st on the web, ORTHO SuperSite, June 3, 2009. Autologous chondrocyte implantation (ACI) can provide high rates of patient satisfaction and maintain good outcomes at long-term follow-up, according to a Swedish study presented at the 8th World Congress of the International Cartilage Repair Society in Miami in May 2009. The investigators assessed 224 patients who underwent ACI performed with the periosteum using the Lysholm, Tegner-Wallgren and Brittberg-Peterson scores preoperatively and at 3 years and 10 to 20 years postoperatively. The study group had an average follow-up of 13.8 years. The investigators found a statistically significant improvement in all of the outcome measures at 3 years compared to baseline results. A comparison of mid-term to long-term results showed that the Lysholm score changed from 73.64 to 69.49. The Tegner-Wallgren score shifted from 8.4 at 3-year follow-up to 8.2 at long-term follow-up, and the Brittberg-Peterson score moved from 31.29 to 40.87. At long-term follow-up, 73% of the patients reported that they felt better or the same compared to the 3-year follow-up. In addition, 92% of the patients reported that they would have the procedure again. Read more ...
ACI Complications:
Further information on ACI surgery, rehabilitation and outcomes:
CKC Patient and GP information on ACI surgery:
ACI rehabilitation information:To get maximum benefit from ACI surgery, you should adhere to specific rehabilitation programme. This may
include weight-bearing restrictions, limited range of motion, and numerous muscle strengthening exercises
which will progress very slowly initially. However, when you successfully complete your rehabilitation, you
should be able to resume normal activities, including most sports.
Further information on chondrocyte culture:ACI after MicrofractureAt the AAOS 2008 meeting in San Francisco Dr. Tom Minas reported the findings of a study, conducted at the Brigham and Women’s Hospital in Boston, Mass., that compared the results of ACI following a marrow stimulation technique (Microfracture) versus no significant treatment (including simple debridement) performed on the same cartilage defect. The results indicate that marrow stimulation techniques may compromise the successful outcome of future ACI. Investigators collected data from 329 consecutive patients treated with Carticel for large and multiple defects (4.8 cm2 per lesion and 8.7 cm2 per patient) and had at least two years follow-up. They concluded that patients who had a previous marrow stimulation technique and were subsequently treated with ACI were three times more likely to fail than patients who had not undergone a marrow stimulation technique prior to treatment with ACI. "The data show that in this patient population marrow stimulation techniques like microfracture are not benign and can compromise a patient’s ability to benefit from a subsequent treatment with ACI, effectively limiting their future treatment options," said Dr Minas, an internationally renowned orthopaedic surgeon for his extensive work in the field of cartilage repair and principal investigator in this study. “Orthopaedic surgeons should reconsider using marrow stimulation techniques as first-line treatment for patients with larger chondral lesions. These techniques should be reserved for patients with smaller defects, in younger patients, where a good result is more predictable.”
Return to sports after articular cartilage repairThere are very few guidelines regarding return to sports following articular cartilage repair. The decision to return an athlete to full activity should be based upon adequate tissue healing, complete osteochondral integration, and sufficient functional rehabilitation. It should be noted that the following recommendations are a summary of various expert opinions (see table below). Unrestricted return to play after microfracture is recommended after three to six months and can be as long as nine to 12 months. Return to sports after ACI/MACI is recommended after 14 to 18 months. Return to unrestricted sports after osteochondral autograft or allograft transplantation may occur earlier than that of other techniques but is dependent upon subchondral bone incorporation. An athlete may return to play when full range of motion has been demonstrated, 80 quadriceps function compared to the uninjured side, and a minimal effusion. This often requires six months. * Only one multicenter study to date has researched return to sport after ACI: Mithöfer and coauthors studied the ability of 45 soccer players to return to soccer in a 40-month (±4 months) follow-up period after ACI. They found that despite 72% of players reporting good to excellent knee function, only 33% were able to return to soccer. What is unclear is whether the two thirds of players who did not return to soccer were clinically unable to return to play or whether they either chose to switch to a lower-impact activity or opted not to return to sport at all. The definition of “ability to return to sport” and the relevance of current outcome measures to sporting participation require further exploration and clarification. Younger age and shorter preoperative duration of symptoms were also shown to significantly improve the ability to return to soccer. However, this improved potential to return to soccer could well be due to a greater influence of psychosocial factors and changing life priorities rather than to physiological properties such as healing and chondrocyte maturation. Bowen et al. in their article on return to play after chondral injuries to the knee, highlighted the fact that the success of rehabilitation is multifactorial and recognized that psychosocial factors such as patient motivation were important contributors. Drawing heavily on self-determination theory, it is proposed that the type of motivation for returning to sport (internal vs external) is an important factor, not only in determining whether the athlete does return but also in the outcome of the return. Recent studies that have considered re-entry into sport after career-threatening injuries have shown that reinjury concerns are significantly implicated in the prevention of an athlete returning to sport (N. Walker, unpublished data, 2005). Emotional response to athletic injury should be considered in connection with return-to-sport goals for ACI patients, both preoperatively and postoperatively. ** MRI imaging is frequently advised prior to clearance to assess graft integration and subchondral activity.
General information on articular cartilage repair:
International Cartilage Repair Society website:
This page was updated on 3 December 2009 Site last updated on: 01 Feb 2010
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The clinical, MRI and functional outcome studdies are very scarce. In 2009 Spalding and collaborators reported early UK clinical experience with 2 year results of articular cartilage repair in the knee using synthetic TruFit CB plugs (Smith and Nephew UK).
26 patients have undergone cartilage repair in the knee using TruFit CB Plugs. All patients have been prospecitively analysed collecting demographic, operative, clinical and MRI radiological outcome assessment. Data was collected at 12, 18 and 24 months post implantation. Protected weight bearing was advised for 4 weeks and sport avoided for 3 months.
At 12 months the mean Tegner activity score improved from 2.4 to 6 (p =0.009). The mean Lysholm score improved from 48.3 to 71 (p = 0.008) and IKDC subjective scores improved from a mean of 37.7 to 65.1 (p = 0.004). KOOS outcome data showed statistically significant improvement in all domains with the mean KOOS sport and recreation score improving an average of 46 points (p<0.001). Within the SF-36 Health Outcome measures, the physical component score (PCS) improved from 39.5 to 50.3 (p = 0.018), and the mental component score (MCS) showed no significant differences, changing from 52.1 to 51.3 (p = 0.37). At 24 months all paramaters show a trend for further improvement but not statistically significant. MRI imaging on this series has shown reformation of the subchondral lamina and T2 Mapping has shown tissue values similar to normal surronding cartilage by 9 months.
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with knee problems. Neither Chester Knee Clinic nor Vladimir Bobic
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