The top level of the treatment pyramid is surgical intervention. Some surgery just replaces the entire joint or alleviates pain whereas other surgical options aim to repair the damaged cartilage, either by prompting spontaneous repair or inserting newly formed cartilage.
Debridement is one such surgical technique which aims to temporarily relieve OA patients of the pain they are suffering (Hunziker, 2002). Osteotomy is also used to reduce pain and improvement alignment of the joint; however it is only recommended for OA patients who also have deformities (Hunziker, 2002).
102 Microfracture, on the other hand is a technique used to initiate spontaneous repair of the damaged articular cartilage (Hunziker, 2002). This involves drilling small holes in the joint, throughout the cartilage lesion, down to the subchondral bone (Hunziker, 2002). This encourages the spontaneous repair response and a blot clot consisting of a fibrin matrix forms and fills the defect (Hunziker, 2002). Subsequently mesenchymal cells penetrate the matrix and the clot is converted to a vascularised scar-like tissue (Hunziker, 2002). The disadvantage with this repair is that the tissue formed is more like fibrocartilage and as such is mechanically inferior (Hunziker, 2002). It also begins to degenerate after a few weeks (Hunziker, 2002).
Autologous chondrocyte implantation (ACI) is an established treatment for cartilage lesions that are larger than 4cm2 (Schulze-Tanzil, 2009, Oldershaw, 2012, Steinert et al., 2012). It is also used as a secondary treatment where microfracture has failed (Steinert et al., 2012). This technique involves harvesting cartilage from a non-loading bearing surface and isolating chondrocytes from it (Richardson et al., 2010, Steinert et al., 2012). These chondrocytes are then expanded in monolayer before injecting the cells back into the patient (Brittberg, 2008, Brittberg, 2010, Zeifang et al., 2010, Oldershaw, 2012, Steinert et al., 2012). The major problems with this technique include dedifferentiation of the cells during monolayer culture, calcification and cell leakage (Steinert et al., 2012). The first version of ACI was ACI
103 with a periosteal flap (ACI-P) (Zeifang et al., 2010). This involved covering the defect (once filled with chondrocytes) with a periosteal flap and sealing it with fibrin glue (Zeifang et al., 2010). There were many disadvantages to this technique, including the requirement of a second surgical procedure to obtain the periosteal flap and sutures to secure it (Zeifang et al., 2010). The chondrocytes in the defect were also unequally distributed using this method (Zeifang et al., 2010). ACI-P was subsequently modified to use a flap made of porcine type I/III collagen (ACI-C) (Zeifang et al., 2010). The latest ACI modification is matrix-induced autologous chondrocyte implantation (MACI) (Zeifang et al., 2010). With this technique chondrocytes are embedded in a biological scaffold and implanted and secured into the defect with fibrin glue (Zeifang et al., 2010). Bartlett and colleagues (2005) compared the outcomes of ACI-C and MACI used to treat osteochondral defects in the knee. All patients complained of pain and limited function prior to the operation. The average defect size was 6.0cm2 in the ACI-C group and 6.1cm2 in the MACI group. The majority of patients had good repair tissue one year after the procedure in both treatment groups; however the most of the tissues contained fibrocartilage (Figure 1.9) (Bartlett et al., 2005).
104 ACI-C Excellent Good Fair Poor MACI Excellent Good Fair Poor ACI-C Hyaline-Like Mixed Fibrocartilaginous MACI Hyaline-Like Mixed Fibrocartilaginous a b
Figure 1.9: Comparison of ACI-C and MACI treatments for osteochondral defects in the knee. (a) Charts indicating the grade of the repair tissue, 24 patients
and 18 patients were assessed in the ACI-C and MACI groups respectively. (b) Charts indicating the type of repair tissue, data represents 14 patients in the ACI-C group and 10 patients in the MACI group. Charts were generated based on the data given by (Bartlett et al., 2005). The reason behind differing patients for each assessment is not clear. ACI-C (autologous chondrocyte implantation with a collagen flap) and MACI (matrix-induced autologous chondrocyte implantation).
Another research group compared the outcomes of knee defects treated with ACI-P or MACI (Zeifang et al., 2010). Inclusion criteria for the study were patients aged between 16 and 50 years with defects between 2.5cm2 and 6.0cm2. At six months after the operation, defect repair and filling was more extensive in the MACI treated patients. However at 12 months, knee function was significantly improved in both
105 treatment groups and similar knee function was also seen at 24 months. Hypertrophy was observed more frequently in ACI-P treated patients but more MACI treated patients required revisions after the initial operation (Zeifang et al., 2010). These results seem to suggest that, although MACI is perceived to be an improvement on the original ACI technique, the restoration of the function of the affected joint is actually similar between the two treatments. Another paper details the histological quality of MACI repair tissue in the knee (Enea et al., 2012). For this study lesion size was 2cm2 or greater and follow-up biopsies were taken six months after the MACI procedure. Authors report that when biopsies were taken, 14 out of 33 biopsies were taken from asymptomatic patients, whereas the remaining 19 were taken from patients experiencing a recurrence in or persistence of their original symptoms. Out of these biopsies, 30.3% were classified as normal, 51.5% as nearly normal, 12.2% as abnormal and 6.1% as severely abnormal. The authors also state that 21% of biopsies contained mostly hyaline matrix, 6% were mostly a fibrous matrix and another 6% were a mixture of the two, with fibrocartilage often on top of a layer of hyaline cartilage (Enea et al., 2012). This again indicates that although improvement was seen in some patients, MACI does not repair damaged cartilage back to its native form in many cases. Although ACI has undergone several modifications since it was introduced in 1987, repair of damaged cartilage is still a major challenge for orthopaedic surgeons (Filardo et al., 2013).
106 The final surgical option is joint replacement. In fact, total hip replacement is frequently used to treat end-stage OA (Mellon et al., 2013). This procedure is now very common, with 71 672 total hip replacements being undertaken in 2011 in England and Wales alone (Mellon et al., 2013). Although the survival of the replacements are very good (90% - 95% last for up to ten years and approximately 85% last for up to 20 years), they can still fail (Mellon et al., 2013). Failure can be for a variety of reasons, including infection, dislocation and aseptic loosening, with the latter being the most common (Mellon et al., 2013). Total knee replacement is also a common treatment for OA affected joints (Liddle et al., 2013). In the USA, 676 000 total knee replacements were carried out in 2009 and this figure is expected to increase to 3.5 million by 2030 (Liddle et al., 2013). This procedure is well-established and can be considered to be the gold standard treatment for knee OA but it may not be appropriate for every patient (Liddle et al., 2013). A recent study followed patients that had undergone total ankle replacement for end stage ankle OA (Rosello Anon et al., 2014). At the final follow-up (this varied between patients but averaged at 37 months after surgery), 15 patients were satisfied with the outcome of the surgery, 1 patient was satisfied with reservations and 2 patients were dissatisfied (Rosello Anon et al., 2014). In another study 114 out of 225 patients were found to be dissatisfied with their knee replacement (Ali et al., 2014). Those dissatisfied were found to have a lower range of motion and higher levels of pain, anxiety and depression (Ali et al., 2014). These studies suggest that total
107 replacement of a joint affected by severe cartilage damage and / or OA can be very effective for some patients but they are not the best solution for everybody.
Even current surgical treatments don’t successfully restore the joint back to its native state and in some cases the repair tissue is of poor quality (Stoddart et al., 2009). Therefore current research is looking into other ways of repairing cartilage, mainly tissue engineering and regenerative medicine.