Brittberg developed the idea of cartilage transplantation, I think it was 1982, and he came up with this landmark paper and it does sound very convincing.

That is, you take some articular cartilage, you send it off to Gothenburg - which is where the main laboratory is, and tens of millions of cartilage cells are generated and then put onto a matrix of some sort and then re-implanted into the patient.

In its first form it was a much more difficult operation to carry out because it was ACI done by an injectable solution of cells which were placed in a defect and then a periosteal patch was sewn over the top – so it was periosteal ACI or PACI. That was a very difficult operation to perform. Then along came ‘matrix’ ACIs (MACI) – the idea of taking a collagen matrix, applying the cells to that and having that just to stick down. Instead of having to take some periosteum and go to the trouble of micro-suturing that into position with something like 20 tiny sutures, you could take some biological glue (fibrin glue) which you squirt into the defect, you cut out the shape of the matrix to the right shape and you literally just put your thumb over the defect as the second stage and you implant the cartilage cells.

complexity
 
That sounds fantastic. If you look at the two big centres in the UK – Stanmore and Oswestry – where millions of pounds have been pumped into generating results, they have very convincing results. Also Tim Spalding has some fantastic data from his series in Warwick where he has done massive or small cartilage transplantation in combination with other surgery such as meniscal transplantation, you see the presentations and you see the results and they are very convincing.

But actually a lot of very good knee surgeons have abandoned ACI. Peter Myers, who I worked with in Australia, did a few during my fellowship year and he was quite disillusioned with the results because it’s very hit and miss.

The technique itself is really straight-forward - it is not a difficult operation. You do an arthroscopy, you take a biopsy from an area where the patient is not going to miss it (like the notch), you send that off. You then get given a nice sheet of tissue. It is very clear which way is up and which way is down because it has a tiny piece missing from the bottom right hand corner, and when that little piece that is missing is in the bottom right hand corner you are facing the right way up. It also has a rough surface which is the cellular surface and a smooth surface – and it is very difficult to put it in the wrong way round. Actually cutting it out for the patient is very easy, repairing the defect is very easy – it is done through an arthrotomy, opening the knee up and through a small incision gaining access to the defects which tend to be two classic positions that are very accessible – the medial femoral condyle or the lateral femoral condyle. Obviously there are other areas such as the trochlea and even the patella, where it is used, but most of those areas are very accessible. So it is technically easy to get to the defect, easy to prepare the defect, this stuff just turns up literally in a little pot. You take it out, cut your template, cut the bit to the size of the template, squirt in your glue in the implant, hold your thumb on it for three minutes and then you cycle the knee, and the bit doesn’t move, you are done.

So it is a very easy operation. But it is extremely expensive. If you look at the results, a very good paper came out by a Scandinavian surgeon called Knutsen, and he did a randomised controlled trial comparing MACI with microfracture at 5 years.

J Bone Joint Surg Am. 2007 Oct;89(10):2105-12.

A randomized trial comparing autologous chondrocyte implantation with microfracture. Findings at five years.

Knutsen G, Drogset JO, Engebretsen L, Grøntvedt T, Isaksen V, Ludvigsen TC, Roberts S, Solheim E, Strand T, Johansen O.

"Both methods provided satisfactory results in 77% of the patients at five years. There was no significant difference in the clinical and radiographic results between the two treatment groups and no correlation between the histological findings and the clinical outcome. One-third of the patients had early radiographic signs of osteoarthritis five years after the surgery. Further long-term follow-up is needed to determine if one method is better than the other and to study the progression of osteoarthritis."

 

This is the paper that we put our hats on and we thought, ooh that’s interesting!

Now actually if you look at more recent studies, there is a suggestion that perhaps at five years that’s not the case, at two years perhaps the MACI is doing slightly better. Interestingly in centres such as Stanmore, originally when the trials were set up there 10 years ago all the patients had to sign up to having a second-look arthroscopy at 12 months and a biopsy, there was very little clinical correlation who was doing well and what it actually looked like. So you could have a patient who said “my knee feels fantastic” and you look inside the knee and it’s like nothing has happened – no fill-in, the thing looks terrible, waste of time – and yet the patient is doing brilliantly and is delighted! Then you can have another patient who has an absolutely perfect fill-in – you can hardly detect where the MACI was carried out – and the patient is unhappy.

I am not saying this procedure does not have its place, and I think it does, but it is not the holy grail. It is very interesting, you see patients coming in every couple of years with their Daily Mail and asking “what about this cartilage transplantation business?” And it has not really changed 1992. At least two of the surgeons I look up to have stopped doing it, and one of them, Neil Thomas does not feel that it does any better than a well done microfracture. There is maybe something to be said for the expert who is doing this all the time, and maybe has the set-up for rehab and is getting slightly better results – because it is so expensive, maybe the right thing to do is to feed patients in to centres like this. In my hospital I was the surgeon who had the licence to do it, and I had 8 patients who were lined up for this procedure, and with changes in the finances of our PCT it was no longer funded in our hospital so I handed all those patients on to Stanmore. I still feel it has a place, but patients really need to have an understanding that it has its limitations and its success is in no way guaranteed. In terms of risks – infection, bleeding, blood clots, the anaesthetic, stiffness, and so on – but actually as a procedure it is very safe. There isn’t anything particularly dangerous about it, like rejection, infection and so on – but one cannot guarantee to the patient that the outcome will have been cost effective. Actually one complication that you do occasionally see is an almost over-reaction, when you look inside the knee and there is an over-filling of fibrocartilage but that is the only potential ‘complication’ that is unique to the operation.

One thing we are now beginning to look at is how to control the environment of the knee joint to help cartilage to heal, and meniscal tears to heal, almost to switch the knee of from being in an unfavourable mode to being in a favourable mode to encourage cartilage healing and meniscal tear healing. A lot of work is being done on the actual synovial lining, where things like PRP come in – platelet rich plasma – and other substances that will enhance healing and switch off inflammation. That is rather than looking at the defect looking at the knee joint as a whole. There was a fantastic lecture at the BASK meeting, in Wales in February/March time (2011) and Daniel Saris is the chap that is now the chair of the International Cartilage association and he gave this lovely lecture on where we are going, and it is the holy grail for surgeons, ie regenerating lost cartilage, lost joint surface, and we are now moving in the right direction and I think there will be some big new breakthroughs in the next decade or two.

 

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