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Early adopters tout biologic treatments for RC tears; others say wait and see
Treatments range from xenograft and allograft tissue scaffolds to growth factors. Watch for fibrin, protein and new growth factor options in a few years.
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Many surgeons now look to biologic rotator cuff treatments — especially scaffold products — to augment surgical repair and enhance deficient native tissue. And they are doing so even though studies backing the efficacy of these products rarely run much beyond two years.
Why such early adoption? In many cases surgeons see little downside given unattractive options. Challenging tendon transfers, arthroplasties using “reverse” shoulder prostheses — even the procedure in which surgeons simply clean up the cuff area and wait to see what happens — have left many eager for alternatives.
“None of these things worked,” said Stephen J. Snyder, MD, of the Southern California Orthopaedic Institute, Van Nuys, Calif. “You won’t find anywhere a consensus by any group of shoulder surgeons that any of these things are of any value. They’re last-ditch efforts that are almost always going to fail.”
Shoulder surgeons agree that a good biologic environment helps a torn rotator cuff (RC) heal better. That remains true whether a surgeon is doing arthroscopic or open surgery, primary or revision procedures, or tendon transfers. Many surgeons now help create that good environment using a range of biologic implants — bioscaffolds — to fortify the tissue of the surgically treated rotator cuff as it heals.
With 250,000 RC repair procedures done every year in the United States, these early adopters are becoming a dependable market for these products. Yet even as the products make their way into the OR, concerns about evidence-based medicine remain. And so it is likely that for every surgeon using one of these products during RC surgery, there is a long line of others waiting for longer-term results before they will act.
Research is already underway for the next generation of biologic options, and many clinicians in both camps eagerly await the introduction of biological or cellular solutions like gels and bone morphogenetic proteins (BMP), autologous materials and other growth factors that could aid healing.
Good biology
The backbone of any of these biologic approaches lies in a good surgical technique done using an open, mini-open or arthroscopic approach, and working with the best cuff tissue possible, including achieving a large footprint for the RC to heal to the bone. “What we will do is simply abrade the greater tuberosity to create bleeding. It’s a biologic environment to promote healing,” Brian J. Cole, MD, said in a recent presentation.
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“We create a footprint where we can lay that rotator cuff over. Whether you use a single row or a double row [of sutures], it doesn’t matter probably. But, what we do have to do is establish the biology in an effort to get that rotator cuff to heal,” said Cole, who is at Rush University Medical Center in Chicago.
“Clearly, the other very important variable is the tendon quality, which is often compromised, and despite the presence of an excellent biologic environment, it may still be the limiting factor,” he added.
Patch it up
Several major orthopedic companies have introduced tissue scaffolds to help augment such surgery. Wright Medical Technology has a human skin-based product called GraftJacket available in a few thicknesses. Stryker’s single-layer TissueMend graft consists of a non-crosslinked acellular membrane made from fetal bovine skin.
The Restore porcine small intestine submucosa (SIS) patch, manufactured by DePuy, a Johnson & Johnson company, probably has — at two years — the longest clinical experience. It is a circular, 10-layer implant (63 mm diameter). Arthrotek’s CuffPatch is another SIS device, and sources say more companies plan to introduce similar products.
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Last month, Zimmer acquired from Tissue Science Laboratories PLC [Aldershot, England; Covington, Ga.] rights to market a durable porcine-derived dermis material that the FDA cleared in 2001. According to a press release, the Zimmer Collagen Repair (ZCR) patch resists collagenase activity and breakdown and “also offers reduced inflammatory response characteristics.” Some researchers have reported inflammatory problems with some xenographic scaffolds.
The ZCR patch implantation technique is reproducible and effective, Gregory P. Nicholson, MD, said in the release. He is also at Rush University Medical Center. “It has only taken 12 to 15 minutes to trim and suture in the graft after RC repair, so it does not add any significant OR time.”
Jury still out
Despite early yet promising results with these materials, Nicholas A. Sgaglione, MD, said the jury’s still out on any scaffold methods of repairing RC tears. He is working to find an alternative with developers at Cascade Medical Enterprises LLC to introduce growth factor-based products to help heal RC tears. He believes this approach could reach clinical application in about two years.
“There’s a lot going on to be able to help manipulate healing, doing so in a practical one-step point of intervention,” said Sgaglione, who practices in Manhasset, N.Y. “Application of potential autologous growth factors is beginning to be applicable and is currently being investigated.”
One novel technology on the horizon that captures autologous growth factors relies on spinning down a platelet-rich fibrin matrix to further remove the red blood cells and produce a 3-D construct. This leaves “the majority of the platelets that are rich in growth factors,” Sgaglione said. What results from the process is a tissue-paper-thin, volume-stable matrix rich in platelets that is suturable and can be delivered arthroscopically to the tissue repair site.
He envisions eventual applications of this same matrix in articular cartilage and meniscal repair surgery.
Thrombin-aided release
As for RC surgery, researchers are looking at augmenting autologous tissue grafts with a platelet-rich fibrin matrix: “Clinical trials are ongoing and product characterization is expanding,” Sgaglione told Orthopedics Today.
Other research has focused on ways to use bovine and nonbovine thrombin to assist in the release of the growth factors from the platelets. “We’re actually using a nonbovine thrombin method,” he said. It involves use of sodium citrate, proprietary gel and calcium chloride, some of the same chemicals used for years in blood donation. Compared to using bovine thrombin, this technique may yield a more sustained release of growth factors without the potential for antigenic reactions.
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All of this research, however, is in the early stages, and much of the scientific concepts behind the development work amounts to theoretical speculation, Sgaglione pointed out. And, although he is currently using this new nonbovine thrombin approach in select patients, what determines if and when it reaches widespread clinical application are such factors as cost, regulatory issues and results of any clinical trials into its efficacy.
“Biological enhancement is the key to healing the RC,” said James C. Esch, MD, of Oceanside, Calif. “The future will include arthroscopic delivery of biological growth-promoting agents to promote healing of the greater tuberosity bone to the cuff tendon.”
Among the most promising options are platelet-derived growth factors, BMPs, angiogenic sutures and chemicals, Esch said. He has already used platelet-derived growth factors in several cases. But, as with all biological solutions in medicine today, dosing and delivery still have to be worked out, said Esch, who is a member of the Orthopedics Today editorial board.
Soon, such biologic agents will be highly sought after for the tenodesis effect they produce in the RC area, particularly when used for fixing large tears when there is significant muscle atrophy, he said.
Restore graft trial set
Although several tissue scaffold products are available for repairing RC tears, sources said clinical trials have not been conducted on any of them yet. Simon Frostick, MD, in the Musculoskeletal Science Research Group at Royal Liverpool University Hospital in Liverpool, England, told Orthopedics Today a multicenter prospective randomized trial involving the Restore patch is scheduled to begin in a few months. He will be the lead investigator for the non-U.S. portion of the study.
Restore investigators will use the implant as a biologic layer during open surgery in patients older than 45 years who have reparable tears, suturing it in place prior to closing the incision. They will randomize patients to receive the patch once the surgery is completed in order to eliminate bias from investigators deciding intraoperatively which patients may or may not benefit from the SIS implant.
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Until the trial is complete, “All we can say is that the patch is safe and anecdotally surgeons report they believe there is beneficial effect,” said Frostick, who is now completing the associated pilot study. Results of the animal studies suggested the SIS implant should have a positive effect in humans, he said.
Patch results
The Restore patch played a big role in the biologic approach to soft tissue repairs that James P. Gurtowski, MD, chief of orthopedics, has spearheaded at Huntington Hospital, Huntington, N.Y. Surgeons there completed 45 cases with the patch over the last two years, Gurtowski told Orthopedics Today.
“I started to use this Restore patch after discussing it with Stephen Badylak, DVM, MD, PhD, who is a veterinarian and medical doctor, who basically did all the research on this product. … Apparently this material will differentiate into any fibrous tissue that you attach it to, not just the RC, and any type of muscle cell,” said Gurtowski, who is aware of members of his orthopedic surgery department using the bioscaffold off-label during revision total hip replacement (THR) surgery. When used to augment the external rotators during THR, it helped reduce the risk of dislocation. “It’s significantly reducing our rate of re-dislocation in these chronic cases, so it has a lot of different applications,” he said.
Although the patch is biocompatible it is a xenograft, which has caused some of Gurtowski’s patients to develop a slight inflammatory response to it. But that resolved in about three to four weeks in all cases. Otherwise, there have been no complications with it and no patient has ever refused getting the xenograft, he said.
Reasonable alternative
Some of Gurtowski’s patients are now out two years and he feels their repairs are better than those of his other patients treated for RC tears. “There are effects of the scaffolding and biologics of the material that create an environment that is conducive for the tissue to heal,” he said. The patch, he explained, simply helps extend his ability to repair the tear at the proper insertion.
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“I think that this is the beginning of an exciting time in orthobiologics. I really pushed it at our hospital. People want this. People really don’t want metal in their bodies if they can avoid it.”
Despite all the enthusiasm, critics abound. “The issues that surround the use of these devices are many, and unfortunately I think we all have more questions than we have answers right now,” said Leslie S. Matthews, MD, who heads the arthroscopy section of the Orthopedics Today editorial board and is chief of orthopedics at Union Memorial Hospital, Baltimore. He is familiar with these grafts, having performed some early studies on DePuy’s now-abandoned ACL scaffold graft product.
With so many unknowns, he and others adopted a wait-and-see attitude toward these new graft materials. “I believe orthobiologics may play a role in the healing of certain select cases of rotator cuff tears. Certainly we find ourselves confronted with situations where the tissue that we are asked to try and repair and which we have to work with is either deficient or sometimes even nonexistent. And, we are looking for ways of augmenting or replacing that deficient tissue. … I don’t think that the science right now clearly guides us in terms of what role these various devices can or should play,” he said.
Matthews admits that the Restore patch and other rotator cuff grafts may be useful tools and that the science behind the Restore product is solid. But, he adds, “I don’t think we have a clear road map of the best way to use it yet.”
Among those issues he wants resolved before using these materials in patients are the high cost and a proven arthroscopic delivery method. “I think that we will get to the point where we not only have a biologic matrix like Restore to use, but we’ll also have factors and other stimulants that will further enhance healing and maybe make these devices more effective.”
Dr. Cole is a paid consultant to Zimmer.
Dr. Esch is a consultant to Wright Medical Technology.
Prof. Frostick is a paid consultant to DePuy Mitek.
Dr. Sgaglione is a paid consultant to Cascade Medical Enterprises.
Dr. Snyder is a paid consultant to Wright Medical Technology.