On 5^thJune I headed over to Rome for the ICRS Focus Meeting on ‘One Step Cartilage Repair’. I was honoured to be invited to give a lecture outlining my nearly 10-year experience of using Chondrotissue for articular cartilage grafting, and I presented in front of an audience of a few hundred specialist knee surgeons from across Europe and beyond.

It was daunting to see some of the world’s top knee surgeons there, including Professor René Verdonk, from Belgium (the Godfather of meniscal transplantation), Professor Mats Brittberg, from Sweden (the Godfather of ACI) and Professor Kevin Stone, from San Francisco (the originator of the term ‘Biological Knee Replacement’). However, all of them are actually just really nice people, who are all just trying to constantly improve the quality of care that they provide for each and every one of their patients.

The topic of the meeting was ‘One Step Cartilage Repair’, with an emphasis on the use of scaffolds and ‘orthobiologics’, which is the field of promoting and enhancing healing through the use of cells and growth factors.

Autologous Chondrocyte Implantation (ACI) and then its successor, Matrix-induced Autologous Chondrocyte Implantation  (MACI) have been in use for about 2 decades now. ACI/MACI is a 2-stage cartilage repair technique for large (>2cm²) full-thickness articular cartilage defects. The first stage involves harvesting some cartilage cells from the patient’s knee, from one of the non-weight-bearing surfaces. These cells are put into a serum and send to a lab. In the lab, the cells are then cultured and multiplied, which takes at least 6 weeks. After this, the cells are then sent back to the hospital for surgical implantation. With 1^stgeneration ACI the cells were injected under a patch of periosteum. However, this led to too many cases of cartilage overgrowth. 2^ndgeneration ACI was therefore developed, and this involved the use of collagen patches instead of periosteum. 3^rdgeneration ACI (MACI) was then adopted, and with this the cultured cells were pre-placed into/onto a collagen membrane. Reported results are good, with success rates in the region of about 80% at 5-year follow-up being seen.

However…  NICE initially failed to endorse ACI/MACI, plus most of the UK private medical insurers refused to fund it. Therefore, with time, ACI/MACI simply became commercially non-viable, and therefore the companies providing ACI/MACI ended up withdrawing from the UK market.

More recently, last year NICE too another look at ACI/MACI, after a challenge led by Professor Leela Biant, from Manchester. Professor Biant produced a clear and compelling argument, based on the large body of evidence within the published scientific literature and also based on cost-effectiveness of treatment, and in recognition for her outstanding efforts Professor Biant was awarded Lifetime Honorary Membership of the UK Biological Knee Society. Thankfully, NICE saw sense, and with their appraisal TA477, we finally saw ACI/MACI formally recognized as a safe, clinically effective and cost-effective treatment in the UK.

Unfortunately, however, by the time that NICE finally saw sense, the damage had already been done, with thousands of patients in the UK having been denied access to the most appropriate treatment for their knees, and with ACI/MACI no longer being available, commercially.

Thankfully, within the hiatus caused by the above fiasco, a phoenix did rise from the flames, and, as they say, necessity is the mother of invention… And with the absence of MACI we saw the development of newer surgical techniques for single-stage (one-stop) articular cartilage replacement, in the form of ‘AMIC’ – Autologous Membrane-Induced Chondrogenesis’…

Microfracture has been around for decades. In its earliest form, this was called Pridie drilling, but the procedure was then popularised by Steadman, from Vale, as ‘microfracture’. This simply involves punching 2mm holes through the subchondral bone plate at the base of a full-thickness cartilage defect, in order to allow the blood and bone marrow cells from the underlying bone to bleed into the defect, creating a ‘superclot’ that is rich in ‘stem cells’. This then grows new tissue over the course of several weeks, whilst the knee is initially offloaded.  Microfracture is quick, cheap and easy. However, the new tissue that grows is ‘fibrocartilage’, which is half way between normal cartilage and scar tissue: it is thinner, rougher, less spongy, less slippery and less robust than normal cartilage. However, it’s still better than bare bone.

Microfracture has reported success rates in the region of about 80% at 5-year follow-up. However, these results simply drop off with time, as the fibrocartilage starts to wear away, plus the results are poorer in larger defects. In addition, with microfracture there is damage to the subchondral bone plate that can often lead to raised islands of osteophytic bone forming, instead of fibrocartilage, which can give even poorer results.

The modern version of microfracture is now ‘nanofracture’ (or ‘nanodrilling’) where we use smaller flexible drills to drill 0.9mm-diameter holes through the subchondral bone plate. This has been shown to give better results that microfracture, with less subchondral bone damage, and this is now considered the gold-standard treatment for small (<2cm²) full-thickness chondral defects.

The biggest issue we have nowadays, however, is working out how best to treat the bigger (>2cm²) full-thickness cartilage defects in a knee – but this is where AMIC comes in…

With AMIC we do the following:

• The edges of the chondral defect are debrided back to a smooth stable cartilage rim.
• The base of the defect is debrided down to smooth fresh bone.
• The subchondral bone is then ‘nanodrilled’.
• A scaffold (e.g. Chondrotissue or Chondrogide) is cut to shape and put into the defect.
• The scaffold can be fixed in place either with bioabsorbable chondral darts or it can be sutured around its edge to the adjacent cartilage.
• The scaffold is then covered in Vivostat PRF autologous platelet-rich fibrin ‘glue’.

	Full thickness cartilage defect on medial femoral condyle with edges debrided and stabilised with radiofrequency probe.
	Based of defect drilled.
	Chondrotissue graft.
	Graft cut to size and placed into knee.
	Graft pinned in place with bioabsorbable chondral nails.
	Graft in place, beginning to soak up blood from the underlying holes in the subchondral bone plate.
	Graft covered in a layer of Vivostat PRF autologous platelet-rich fibrin ‘biological glue’.

This technique has been shown to grow better quality tissue than is seen from microfracture, and histological studies have shown that the new tissue from AMIC is ‘hyaline-like’ cartilage, which is the same as what one tends to see with ACI/MACI cases.

The advantages of AMIC over ACI/MACI can be summarized as the following:

ACI / MACI	AMIC
2 separate operations required.	1 single-stage procedure.
Very costly to culture the cartilage cells.	Comparatively much cheaper.
25% of cases require further surgery due to overgrowth of the new cartilage.	Repeat surgery for overgrowth = relatively uncommon.
Logistically demanding processes required and technically demanding surgery.	Far simpler, and hence less to go wrong.
No ‘spares’ available, unless the cartilage is re-cultured again, which then provides lower quality cells.	The scaffolds are readily available ‘off-the-shelf’, should extra scaffolds be required during a procedure.

What comes next?

In the quest to achieve even better and more reliable results, with improved patient outcomes and better quality new cartilage tissue formation, a number of surgeons (particularly in Italy) have been obtaining ‘stem cells’ from bone marrow aspirate concentrate (BMAC), and adding this to the cartilage scaffolds. This is something that we are currently seeking approval to do here in London, and something that we are hoping to be add to our current portfolio of treatments in due course.

and thank you….

and finally, a very big thank you goes to Professor Martyn Snow, from Birmingham, for him kindly having invited me to share my experiences of articular cartilage grafting with so many esteemed colleagues from around the globe at the ICRS meeting in the beautiful city of Rome, which is one of the loveliest cities in the world!

Our view of The Vatican, whilst having drinks before dinner!