Orthobiologics: A New Era for Articular Cartilage Surgery?

Bert R. Mandelbaum, MD, DHL (Hon)

|March 18, 2016

Microfracture Augmentation Procedures

Treatments for articular cartilage problems have come a long way. As I outlined in my last column, not every knee with a cartilage injury should have surgery. And it's never the whole answer.

But for the right patient, surgery can make a huge difference, and the techniques we can offer are getting better, thanks to the availability of orthobiologics—cell-based therapies and biomaterials that promote healing, such as platelet-rich plasma, hyaluronic acid, and stem cells.

The choice of procedure depends a lot on the size of the lesion, the overall health of the knee meniscus, ligamentous integrity, and ligamentous alignment. For smaller cartilage lesions that don't extend to the bone, I have had good success with microfracture, a surgical technique used to repair damaged articular cartilage by making multiple small holes in the surface of the joint to stimulate a healing response.

This procedure has been around since the 1980s, and the short-term results can be very good. Over the years, it has allowed many athletes to return to sport. In the 2000s, we learned that the benefits wane after 2 years, perhaps because the newly generated fibrocartilaginous tissue has inferior biochemical and biomechanical properties compared with normal hyaline cartilage. As a result, the procedure has lost some of its allure.^[1]

But in a modification, called microfracture augmentation procedures, or microfracture plus, we inject platelet-rich plasma, or scaffolds, into the microfractured defect. Scaffolds, which are thought to provide structural support and promote cell adhesion and migration during the repair process, include chitosan-glycerol phosphate blood implants or BioCartilage®, a cartilage extracellular matrix (Arthrex Inc; Naples, Florida). The platelet-rich plasma provides growth factors and other cytokines that stimulate healing of bone and cartilage. The scaffold helps the clot organize itself better and make a better, more hyaline surface.^[1]

BioCartilage is cartilage from a young donor mixed with platelet-rich plasma. It becomes like putty, and you can use it to patch the cartilage defect. There have not been a lot of studies on the donor cartilage, but so far the results are good.^[2]

I give platelet-rich plasma and other orthobiologics not just during the surgery but afterward as well. And this is a key point: We have to think of orthobiologics as something we use in preparation for surgery, during surgery, and then after surgery, all of which make them a supportive adjunct to improve regeneration of the cartilage. The outcomes reported by my patients have improved when I've used this approach.

Osteochondral Autograft and Particulate Autograft

Another approach to repairing smaller cartilage defects is osteochondral autograft, in which we take a bone plug graft from the same patient's knee from an area that is non–weight bearing. In those scenarios, there have been several studies around the world showing significant efficacy.^[3,4]

Next is another group of procedures, called the "particulate autograft," where some of the patient's own cartilage is harvested from another site of the knee, mixed, ground up, and placed into the defect. Typically we take cartilage from a non–weight-bearing surface, such as the notch inside the knee. These procedures are also works in progress.

Each of these procedures works only in patients whose defects are smaller than 2 cm². There isn't one procedure size that fits all. For example, for an 8-mm defect, osteochondral autograft would work well, because you can just take one plug. On the other hand, osteochondral autograft doesn't seem to work well in patients over 30 years of age. And if you're treating athletes who do a lot of jumping, it's not the best bet because you have to take graft material from the trochlea, which may require a rehabilitation period of longer than 9 months prior to full return to play.

Some of the allograft procurement companies have been offering allograft plugs that are 10 mm in size. This development has made this type of allograft more available; previously, one had to wait until a whole condyle became available. Partly for that reason, we've been using osteochondral allograft more frequently for these smaller defects in recent years.

Osteochondral Allograft and Autologous Chondrocyte Implantation

For larger osteochondral defects, I consider two options: osteochondral allograft and autologous chondrocyte implantation.

A classic example is a 16-year-old patient with osteochondritis dissecans. This problem is not caused by trauma but rather by a lack of fusion of the bone during pubescence. As a consequence, a piece of bone and cartilage breaks off, most often in the medial femoral condyle.

This fragment may be floating around in the joint, getting caught in the joint and causing a locked knee. So I remove the fragment, and if it's a big, deep defect, I will need to resurface the defect in the bone and cartilage.

If I'm using osteochondral allograft, it has to be fresh, by which I mean harvested from a cadaver within 28 days. I don't use frozen allograft because freezing kills the chondrocytes.

Cartilage is immune-privileged. It's not like a liver or kidney. There is no immune response to cartilage implants, mainly because the cells are inside the cartilage. This makes working with cartilage implants a lot easier. The patient stays on crutches for 6 weeks. Usually between 6 and 9 months they are ready to return to some activity.

In the past, most surgeons would just get the fragment out and do nothing else. When we first started doing these procedures, we focused on filling in the hole, resurfacing the defect, and telling people, "But don't do too much!" Now we've gotten better at it, partly by using orthobiologics as "fertilizer" that makes the cartilage healthier and gets it to heal to the bone faster.

Over the past 20 years we have had follow-up with many patients and found that tissue survival in the grafts is pretty good. With some of these new techniques, we now can take these young athletes and get them back to a moderate level of activity, and some to a higher level.

The other option for treating large osteochondral defects is autologous chondrocyte implantation. In this technique, we take a piece of the patient's cartilage from a non–weight-bearing surface, harvest chondrocytes, and culture those cells. About 6 weeks later, after we grow them to several million, we reimplant them in the patient under a scaffold, usually made of collagen.

The old approach is to inject the cells under a scaffold patch, covering the hole like a skin. The newer approach is to mesh the cells into the scaffold.^[4]

Autologous chondrocyte implantation and osteochondral allograft both come with advantages and disadvantages. With the larger cartilage defects, especially those that get down to the bone, it's easier to justify the osteochondral allograft. The return to activity is faster with this procedure.^[5]

I use autologous chondrocyte implantation in patients who don't want tissue from a cadaver and whose defects don't include much of the bone. But I've had good success with both approaches, and I'm happy that the tools, techniques, and orthobiologic treatments at my disposal are getting so much better.

References

1.Strauss EJ, Barker JU, Kercher JS, Cole BJ, Mithoefer K. Augmentation strategies following the microfracture technique for repair of focal chondral defects. Cartilage. 2919;1:45-152.

2.Abrams GD. Mall NA, Fortier LA, et al. BioCartilage: background and operative technique. Oper Tech Sports Med. 21;116-124

3.Pánics G, Hangody LR, Baló E, et al. Osteochondral autograft and mosaicplasty in the football (soccer) athlete. Cartilage. 2012;3(1 Suppl):25S-30S.

4.Trinh TQ, Harris JD, Siston Ra, Flanigan DC. Improved outcomes with combined autologous chondrocyte implantation and patellofemoral osteotomy versus isolated autologous chondrocyte implantation. Arthroscopy. 2013;29:566-574.

5.Mithoefer K, Hambly K, Della Villa S, Silvers H, Mandelbaum BR. Return to sports participation after articular cartilage repair in the knee: scientific evidence. Am J Sports Med. 2009;37 Suppl 1:167S-76S.