Virginia Cartilage Institute.

The vertsatility of the Denovo NT implant is well demonstrated in this video clip. The patient presented with a symptomatic lateral condylar lesion well demonstrated by imaging studies. In a single stage procedure, the knee was arthroscoped and the location of a mini-incision well outlined,  The video shows a portion of the procedure, duraton  in real time 44 minutes for (2) lesions.

Platelet rich plasma is enjoying a renaissance based upon excellent clinical experience, the development of new concentration technologies, and a plethora of scientific articles (now over several hundred annually) seeking to establish the correct dose and the right indications.  There is no therapy that will be all things to all people, but it does appear that for many inflammatory conditions and in some situation of tissue degeneration, PRP has a place.

One of the ongoing issues has been the dose. Like any drug, it sure helps if the doctor knows the right amount to give. Older technologies that simply use a centrifuge to prepare PRP have no indication of (a) the patient’s present platelet count and (b) the amount of concentrate produced. If you know both numbers, it is possible to calculate the amount of “growth factors’ that are being introduced. It is only by these type of measurements that we can advance the field and produce improved results for our patients.

The cell counter picture here solves these problems. A small portion of the patient’s blood is pre-tested to determine platelet count and white blood cell count. After concentration, the test is repeated with a tiny sample from the PRP concentrate.  By comparing these values, we can (1) know what we are administering and (2) adjust the Angel machine sensors to either increase or decrease the white cell population.

The last comment is very important as we get to “stem cell” purification.  The advantage of advanced analytics is that we can select out the correct cell population, for example from bone marrow, and establish a reproducible “dose” for the patient. This after all is the essence of quality assurance- verification.

The hype of new kinds of cell therapy will only be realized when the science catches up with the potential…

On a continuing basis I see patients who come to me for “stem cell therapy” based upon their readings in the popular press or on the internet.  Even as we sit on the cusp of this new concept in medicine- that of using stem cells to regenerate body parts- it is also important to realize how early we are at either understanding or exploiting stem cells for medical treatment. For example, we all have stem cells in our bone marrow, but only about one in ten thousand  cells. It is possible to enrich this population using similar techniques that are used for platelet rich plasma, but this level of enrichment needs to be measured before we can understand what the correct “dose” would be, not to mention exactly what the correct kind of stem cells we are seeking. There are techniques for doing both of the above, but much work needs to be done. Some of these techniques, like flow cytometry, can only be performed in a sophisticated research lab.

For example, I saw on 60 minutes Jan 8.2012 yet another medical scam based upon stem cells. Desperate diseases demand desperate measures, I know, but that does not prevent quacks from taking people’s money, and to no avail for the patient. If patients are to inform their choice by using the internet, they had better do their own diligence- a very similar concept to a financial transaction.  Caveat Emptor.

Look for the following: publications in a well respected journal,  presentations at national meetings, animal models with favorable results, clinical trials sanctioned by the FDA; these will at least tell you that the concept is taken seriously.  And always remember the words of Judge Judy, “if it doesn’t sound right, it isn’t true”.

The use of PRP for “regenerative” purposes has been well documented elsewhere for as diverse purposes as cosmesis, hair growth, tendinopathy, heart disease and many other health problems. Scientific evidence in well controlled studies for improved outcomes has yet to be produced for most of these issues. One area in which we will soon seen some early outcome studies is the use of PRP for osteoarthritis, an indication that I have been exploring for about two years.

When investigating a disease as manifold as osteoarthritis (OA), it is important to set the ground rules appropriately. First, the patients need to have IMO mild or moderate disease, not the end stage bone-on bone disease with associated abnormalities- like crookedness and looseness- that cannot reasonably be expected to be helped by injections. If you include these severe cases in a sample, it is a guarantee the results will not be comforting. The film on the right is still acceptable for PRP treatment.

Second, one has to spend time on investigating the precise PRP that is being used- how concentrated is the product- and this varies widely depending upon the manufacturer. To some extent, it may also vary according to the patient’s native platelet count- more on this later. Once we know the dose per injection, then we have to determine the right dosing schedule- how many injections?  In other words, if PRP is to be accepted in the long term, we need to establish a dose-response relationship, as with pharmaceuticals.

Finally, it would helpful to compare PRP with other available injectables. Even though commonly used, I will rule out cortisone as a comparator because of the obvious side effect upon cartilage. Patient’s experience excellent short term results with cortisone injection, but I have seen some of the worst cartilage damage in those joints subject to repeat injections.  I seldom recommend cortisone for that reason.

A reasonable comparator would be hyaluronic acid (HA), now available under many brand names for injection (and also used for cosmetic injections, and for eye surgery).  I have about 10 years experience with HA, and it is effective in pain relief for OA in about 2/3 of patients who try it. The effect can be months or even longer. HA is composed of large, viscous molecules and does not contain growth factors.

A study comparing HA to PRP for OA of the knee is being performed at Rush Medical  at the present time, and we eagerly await the results. Early indications appear favorable for PRP, but this study has not yet been published in a reviewed journal. A similar study performed in Italy has shown excellent medium term results with PRP.

In my opinion, high concentrates (12-14x) of PRP are effective for pain relief due to OA if given to appropriately selected patients. The regimen requires (2) injections over a 2-3 week period. The response rate is approximately 85%, a definite improvement over HA.  The duration of symptom relief is variable, but appears to be in the 6-12 month range.

I look forward to learning more about PRP in 2012 as new studies become available and better analytics allow us to better quantify precisely the dose we are administering.

In scientific publications the use of an anecdote is frowned upon in favor of comparing groups of similar patients with statistic methods.  But this is more of a blog, not a science publication, so if you will put this in proper context I would like to share with you  the story of a young woman with knee pain due to cartilage loss.

Call it a Holiday story, because at the time of this writing you see her here hiking in Israel, pain free.

She came to me about 6 months ago with chronic symptoms of pain that defied all sorts of treatment, including prodigious exercise therapy and nutritional supplements. She is fit and enjoys working out.

The MRI revealed a full thickness loss of cartilage about the size of a quarter

located on the condyle of the femur,  directly on a weight bearing surface. Once the location was confirmed by arthroscopy, a Denovo NT repair was carried out through a small incision. This was performed as an outpatient, and since the patient was visiting from another country she stayed in a local hotel for a few days and then convalesced with family in another state. After a couple of weeks she then flew to her home country and carried out her rehab there. We communicated frequently by email, and the therapist was great at that as well.

In the photo the patient is hiking up a steep hill, pain free.

This result is fairly typical for patients with isolated cartilage lesions. Note how this patient is an excellent rehab candidate, highly motivated, slim in stature and- as with all my Denovo NT candidates- has no arthritis in her knee.

Happy Holidays!

Seldom in today’s environment do we have the opportunity to re-scope a knee that is doing well. In this case the patient sustained a torn meniscus and there was such an opportunity to view the 5 month old Chondrofix Implant, pictured here.

Chondrofix Implanted In Medial Condyle

The implant appears flush with the bone, the matrix layer intact with slight signs of wear. There is no discoloration of the surrounding tissues, and no loose fragments. We will continue to assess durability of these implants over time. At present, I am considering the use of Chondrofix for accessible lesions

in patients who cannot or will not adhere to using crutches for 4 weeks post-op ( see Denovo NT).

Another potential indication for Chondrofix could be those cases of partial knee replacement where a “satellite” lesion is encountered next to the implant. Chondrofix has a shelf life of 24 months and for the latter situation it could therefore be available off the shelf- rather than pre-ordered, which is the case for Denovo NT.

Please see previous posts regarding the Chondrofix implant, which I began trialling in January of 2011. The above picture shows an MRI exam at 5 months post op, demonstrating (2) plugs in place and a good appearance of integration at the bone level. The cartilage surface also looks quite good. This is a very early timepoint and with only a handful of implants out there in the real world it is still far too early to make any assessment about Chondrofix. these patients have been allowed to walk on the knee very early after surgery, almost immediately in some cases. It is not known if this abbreviated period of rehab is a good idea or not. Notice how the reconstructed cartilage surface is flush with the normal adjacent cartilage.

To be clear, the Chondrofix implant, which comes in many sizes, is a sterilized form of allograft. For this reason it has a long shelf life,is returnable if not used, and also has no living cells.  The latter point is what makes Chondrofix sharply different from Denovo NT. There may be some cases where the virtues of a solid reconstruction outweigh the risks; and conversely, there may be instances where the presence of living tissue is preferable. We are currently in the process of working this out. I think the “take-home message” here is that the cartilage surgeon will have multiple methods of repairing the joint surface.

Please see previous notes on this web site regarding PRP.

In the August edition of the Journal of Sports Medicine( ) we now have gene expression evidence of PRP effects for patients with osteoarthritis.

What this may mean is that the potential activity of PRP is, in fact, real.  PRP is  a medley of bioactive proteins, including growth factors that may control protein manufacture. In regenerative medicine, it is precisely the manufacture of proteins that we are seeking to influence.  We know that activated platelet contain over 1000 such proteins;how they may promote healing and regeneration is still very much an issue.

So this study referenced above seeks to measure a precise effect upon DNA.  The effect measured shows a reduction in the inflammatory protein IL-1, a known component of joint inflammation, hence a desirable treatment of osteoarthritis. For those of us who have been treating osteoarthritis with PRP, this is a welcome finding. In part, it explains the favorable clinical result we have been observing.

There is much work to be done. Clearly some genes will be up-regulated and some down-regulated, and it is the balance between the two that needs to be assessed.

Denovo NT: The first Twenty

This is not a scientific article but the time is right for looking at my experience the last 2 years with Denovo NT. Twenty cases are between 4 months and two years out from surgery.  The areas treated have all been either knee or ankle, and the knee has been treated in various locations ranging from the patella to both condyles.. All of these patients had significant pain preoperatively, and all had normal or nearly normal xrays.

The complications have included one blood clot, treated successfully with blood thinners, and one wound healing problem. This at first looked like an infection, but we were unable in spite of several attempts to culture any germs. In the end I washed out the knee and it healed fine. I am always looking for problems attributable to the tissue bank but as of yet I have been unable to document any cases (in over 2500 performed) of a tissue bank related infection, this according to the product manager at Zimmer, Inc.

The results have thusfar been superb. I am seeing early pain relief and good evidence of early “fill” of the cartilage lesions as demonstrated by MRI. Because of this, I am now about to fine tune the rehab program, and in some cases to allow earlier weight bearing (stopping the crutches).  At present, there are no clinical failures;  obviously this needs to be reassessed as  more time passes. To  date, none of the patients has had a secondary cartilage procedure.

One patient comment that keeps recurring is that for those patients who have had microfracture in the past, the Denovo NT procedure appears to offer greater pain relief, and sooner, than what they experienced previously. Of course, these patients did not do well with their microfracture procedure, so the sample is biased.

It should also be noted that I am performing Denovo NT through a very small incision- that last case was 1 ¼ inches long; concurrent with an arthroscopy.  This is important to note when comparing my patients with others who may have been done differently.

At present, I am seldom performing ACI;  the results of the DenovoNT procedures so far appear to be at least as favorable, and for about 1/10 the cost; not to mention one surgery instead of two.

There is an ongoing clinical study of 25 patients with Denovo NT, and the two year results are in on the first four patients.

(Cartilage, online edition, print edition pending:pages 1-8, 2011 Farr, J. & Yao, J: Chondral Defect Repair with Particulated Juvenile Cartilage Allograft)

Pain scores are going down, and activity scores have gone up nicely so far. This is just what one would expect with a successful repair technique.   Furthermore, MRI studies confirm my own

personal results, showing excellent “fill” of the cartilage lesions.

Four patients do not (yet) make a persuasive argument, but the trend is clear. All indications so far are that partculate

cartilage grafting can product very good early term results; no doubt critics will then ask for 5 year and then 10 year results.

Only time can address issues of that nature.