Today, at the TOBI conference in Las Vegas, I presented on percutaneous anterior cruciate ligament repair (Perc-ACLR). This post is an excerpt of that presentation. To view the full Power Point presentation, please watch the video above.
ACL reconstruction (ACLR-the surgery) is a surgical procedure to replace the ACL with a tendon graft. It’s use has exploded in recent years, reaching staggering epidemic levels. We’ve seen more than a 300% increase in the number of women and a 924% increase in youth under 15 years of age getting ACLR surgery. What I hear from patients is that they believe their knee is going to be exactly like it was before they tore or ruptured their ACL. There are three key misconceptions about ACLR that you need to be familiar with:
- Reconstructing the ACL prevents arthritis
- ACL reconstruction will help me return to sports quicker
- My knee will be just like it was before my injury
None of this is true (please see the video for more details and supporting literature). So is there another option? Yes. A percutaneous ACL repair (Perc-ACLR), which is a precise injection procedure that repairs ACL tears using bone marrow concentrate (BMC or a same day stem cell procedure).
ACL Tear Types
There are many classifications and subtypes of ACL tears, but in regenerative medicine, we define ACL tears as partial, full thickness nonretracted, and full thickness retracted. A partial tear is exactly what it sounds like: it hasn’t torn all the way through and a portion of it is still intact. A full thickness nonretracted tear is one in which the pieces of the ACL haven’t pulled back like a rubber band, but the ligament is damaged through and through. In full thickness retracted tears, the ACL has pulled back into two pieces like a broken rubber band. While we can help a minimally retracted ACL tear, bigger retracted tears are beyond the scope of this procedure. Basically, that means that about 70% of all ACL tears that currently receive surgery can be treated with Perc-ACLR.
Choices for Injecting the ACL
In the ACL anatomy, we have two bundles: the anterior medial (AM) and posterior lateral (PL). When injecting BMC into the ACL, we want to get coverage in both the AM and PL bundle, so we’ve have to use specialized imaging techniques to do that. There are four choices we have when injecting the ACL: blind, musculoskeletal ultrasound (US), fluoroscopy (real-time X-ray), and arthroscopy.
Blind means performing injections without using any kind of guidance to assure the needle is where it is supposed to be. We’ve tested injecting blind using US and fluoroscopy to check ourselves. We found that it’s very unlikely that injecting the ACL blind actually results in the ACL being injected.
While the technology is cheap and accessible, one of the problems we’ve seen with ultrasound guidance is that visibility is too limited to properly perform a complete ACL injection. How is the imaging limited? You can only easily see the bottom one-third to one-half of the ACL at the tibial insertion. So there is no way to know if the BMC you’re injecting is reaching the top of the ACL or if it’s dumping out of a tear at the back of the ACL. If the latter occurs, the top part of the ACL likely goes without stem cells.
This is our choice for the Perc-ACLR injection procedure. Using fluoroscopy guidance, you can see the whole ligament and both bundles once they are “painted” with contrast. This allows us to reposition our needle and inject all of the ligament. The negative with this technology is that it’s more expensive than US and requires a specialized shielded room.
You could perform an injection into the ACL while doing an arthroscopy of the knee. The advantage here, like with the fluoroscopy is that you can see the whole ligament. However, it is more expensive and invasive than the other methods, and the bigger issue here is that in performing this more invasive procedure, there is more risk being taken by the patient.
We Use High-Dose Bone Marrow Concentrate (HD-BMC)
When we use BMC, we’re using the high-dose form of in the data I’m covering. What does this mean? First, this is not a standard single draw that pulls 60 cc from a single site, nor is it a draw where you stick the needle in deeper and pull some as you come out. This is a different technique, defined by the bullet points below, that we’ve seen gets a lot more cells than either one of the above-mentioned approaches.
- Multicortical site, low-volume per site BMA (generally 5 cc per pull with two depths at each site and approx. 4–6 sites per side ).
- Final injectate volume from a 60–90 ml BMA is 2–4 cc. We also process it differently, so we’re getting small volumes in higher concentrations.
- Total nucleated cell count (TNCC) is generally >200M/ml.
Our HD-BMC ACL Injection Experience by the Numbers
- Total stem cell cases currently in our registry: 7,802
- Total knee cases: 4,802
- Total number of knee cases where the ACL is injected for any reason, and that includes a lot of cases with just ACL laxity, but no known tear: 758
- ACL for known tear with or w/out another structure being injected (e.g., meniscus): 157
- ACL for known tear and only ACL injected: 37
Our Pilot Study
Our pilot study a number of years ago (J Pain Res. 2015 Jul 31;8:437), consisted of 10 patients with partial and complete nonretracted ACL tears. We saw objective changes in MRIs before and after, and we used computerized histograms to be able to quantify those changes. Seven of ten patients reported clinical improvement.
How long did it take for these improvements to happen? Be sure to watch the video to see the actual MRIs showing the patients’ progressive improvement over time (baseline, 3 months, 6 months, and so on). But the short answer is all of the MRIs showed improvements over baseline, but normal ACL readings varied by individual. For example, in an older patient, we observed a very tight, normal-looking ACL at 9-11 months, while a twenty-something patient got a normal reading on MRI at 3 months.
Larger Case Series
We have a larger group of patients currently submitted for publication. As far as our larger ACL case series is concerned, we’re still seeing statistically significant changes in MRI histograms consistent with ligament healing. We’re also seeing great results.
How Do We Make Regenerative Medicine Reliable?
One of the things that’s very important to us, not only in ACL but also in other areas, like knee osteoarthritis, is trying to make sure that we can make regenerative medicine reliable. A couple of ways we are working on toward this is by grading candidacy based on the data in our clinical registry of what works and what doesn’t and adding additional data beyond just demographics, diagnosis, and MRI. How do we go beyond MRI?
- To predict how arthritis patients will respond to BMC, we measure 25 growth factors and cytokines using microarray, multiplex ELISA and correlate those levels to knee OA BMC outcome.
- We use an artificial intelligence model, which was 84% accurate (just based on the chemicals in someone’s knee in predicting how they would respond) as of six months ago, and a new model will more patients will be run this summer.
Can We Predict If a Perc-ACLR Will Fail?
Moving now from knee arthritis to the Perc-ACLR procedure, what things would predict failure? The patient’s MRI is a good place to begin. In this arena, it comes down to “offset” and morphology to help us predict how someone is going to respond.
Offset is the degree of posterior translation of the femur on the tibia. The ACL is oriented so that it limits that posterior translation of the femur. So the farther back the femur is relative to the tibia, the more damaged the ACL is. So the offset itself is important in looking at whether or not someone is likely to respond. Morphology (how the tear looks), or the structure, of the tear is also important, and we have created a candidacy tool that will be used by our medical network that is based not just on existing offset data but also morphology data.
What NOT to Do for a Professional Athlete: US-Guided BMC Injection
This procedure was done at a famous orthopedics sports-medicine clinic, where a pro athlete was treated. This athlete was diagnosed with an ACL tear and was treated with an ultrasound guided BMC injection, but the procedure didn’t work? Why?
To review a bit more, his original postinjury MRI exhibited some ACL tearing at the origin and insertion, and this was read out by the radiologist as a partial tear. I would have put this ACL tear in the complete nonretracted category. He ended up getting a BMC injection under US guidance at the tibial insertion. He was put back to hard exercise despite this tear and he re-tore quickly.
Six weeks after the US-guided BMC injection at the tibial insertion, at the sports-medicine clinic, we see a blunt and now retracted edge of the ACL. Based on his result, I believe that what likely happened is that, as I mentioned happens with US-guided ACL injections, the BMC went up about halfway and dumped out. So the BMC never reached the origin, the upper part of the ACL, and the part that was never treated, likely, eventually tore and retracted back. So when he finally made his way to me, this guy was not in a good spot. His offset went from a mild 4 to 10+, which means he was experiencing ACL failure. In addition, his MRI had evidence of increasing, rather than decreasing bone bruising (BML). Using fluoroscopy, I was able to get his origin area injected higher up and get a little bit of the stem cells to flow down, and he now seems to be on the mend.
Our ACL RCT
Our ACL randomized controlled trial (RCT) is about halfway recruited, with our recruitment goal being 50 participants with ACL tears. The data is reported in the presentation and the results look very strong. See the video for more details.
The upshot? We’ve seen game-changing results with Perc-ACLR, using precise ACL injections under fluoroscopy. While ultrasound can be used, I wouldn’t use it beyond a partial tear or even just ACL laxity as it’s not really a good standard of care for this procedure. In the meantime, we’ve created a candidacy tool for our network providers to use so that we can ensure that we use this new procedure in patients who are the most likely to respond. We will also continue to publish our research on this remarkable, Perc-ACLR procedure that we pioneered.