Biological solutions for cartilage regeneration in orthopedics are one of the fastest-growing areas of research and development fields in the specialty. While some solutions may seem beneficial in the early stages, evidence-based research trials are emerging to evaluate their longer term benefits. However, those that currently show clinical improvement could be the first step to revolutionizing the way orthopedic care is delivered.
"We're getting closer to biologically modifying the environment of our diseased joints so outcomes can be improved and we can spare patients from having surgery, which is the biggest goal in my mind," says Brian Cole, MD, head of the Cartilage Restoration Center at Rush University Medical Center in Chicago. "We at Rush, in many ways, are spearheading a lot of this research in collaboration with others in the Division of Sports Medicine headed up by Dr. Bernard Bach."Dr. Cole discusses the clinical trials and developments at the forefront of biologics in knee and shoulder surgery today as well as four trials being conducted at Rush that could have a huge impact on orthopedics in the future.
Knee
Cartilage Autograft Implantation System (CAIS). In a recently published study titled "Minced Cartilage Without Cell Culture Serves as an Effective Intraoperative Cell Source for Cartilage Repair," Dr. Cole and his team showed that using small bits of cartilage placed into a small resorbable scaffold can promote re-growth better than most currently-available implants.What sets this technique, the Cartilage Autograft Implantation System (CAIS), apart from the current autologous chondrocyte implantation procedures is the surgeon's ability to make the procedure a one-step process instead of two. Surgeons currently harvest cartilage tissue from the patient and prepare it for re-implantation as a two-step process, a very expensive process requiring two surgeries. Dr. Cole's team has overcome these challenges by preparing a cartilage-loaded implant in the operating room with immediate availability. In the study, chondrocytes grew into an adjacently-placed scaffold materials to produce neo-cartilage in a mouse model.
Since CAIS is simplified into a one-step process and emphasizes regeneration from the time the treatment is indicated or desired, the technique eliminates technical difficulties and high costs associated with alternative procedures such as autologous chondrocyte implantation. In the future, more studies will identify the appropriate parameters of the procedure, such as the size and loading density of the fragments and method of harvest, to optimize the extent of successful cartilage repair.
Comparing CAIS to microfracture. Dr. Cole and a team of collaborating orthopedic surgeons also conducted research comparing CAIS to microfracture for patients with symptomatic chondral defects. In the study, titled "Outcomes After a Single-Stage Procedure for Cell-Based Cartilage Repair: A Prospective Clinical Safety Trial With 2-Year Follow-Up," the researchers found that CAIS shared comparable risks to performing microfracture and progressive improvements during the second year after surgery.
In the study, the average age of the patients in both groups was the same, which means the improvements associated with CAIS aren't dependent on age. Patients were given the International Knee Documentation Committee evaluation and Knee Injury Osteoarthritis Outcome Score at various increments after surgery and the CAIS group consistently showed improvements at 12, 18 and 24 months. From these results, the study's authors determined the procedure is safe and feasible for patients.
Shoulder
Minimizing re-tear rates. A broad spectrum of research regarding biologic solutions for shoulder injuries is now underway, particularly focusing on minimizing the re-tear rates among patients undergoing reconstructive surgery. Dr. Cole has participated in the development of a polyethylene articulated sponge that promotes collagen in-growth to improve tissue regeneration. "We're looking at novel scaffolds that can ultimately improve the repair construct," says Dr. Cole. "There is currently a large propensity for re-tears after a patient undergoes rotator cuff repair and these scaffolds can help promote re-growth. The exact clinical indications for their use continues, however, to be defined."Utilization of soft biologics. Another area of biologic shoulder repair receiving significant attention is soft biologics. Dr. Cole is also currently investigating recombinant human growth factors which could help the body heal if they are injected into the injured region. Another option under consideration is the use of platelet-rich plasma to augment the healing of small tears, as this has been supported to date in basic science laboratory studies.
Current cartilage trials at Rush
1. Biologic implants. Both the Denovo Natural Tissue (NT) and Denovo Engineered Tissue (ET) are being studied at Rush. NT is human issue allograft consisting of particulate juvenile articular cartilage. The ET graft is a three-dimensional hyaline-like cartilage tissue developed by culturing allogenic chondrocytes from juvenile human donors. Both implants are surgically implanted and affixed to the bone at the base of a cartilage defect through a small incision in front of the knee. The NT procedure is currently available to treat symptomatic localized cartilage defects and the ET procedure, which was initially investigated in part at Rush, will be ready for further clinical study near the end of 2011.2. Limited resurfacing implants. The HemiCAP implant is used for limited resurfacing arthroplasty and is designed to match the individual shape of the patient's cartilage surface. In the study, researchers are examining the use of the metallic implant for the treatment of specific focal femoral condyle defects to see whether it provides better outcomes than current treatment options.
3. Arthroscopic partial meniscectomy. In this NIH funded multi-center trial, researchers are comparing the use of arthroscopic partial meniscectomy to non-operative treatment for patients with symptomatic meniscal tears in the setting of concomitant knee osteoarthritis. The trial seeks to identify which, if any, patients would benefit from the surgical meniscectomy over non-operative treatment.
4. Platelet-rich plasma. Dr. Cole is looking at the effects of autologous conditioned plasma, or platelet-rich plasma, on patients who have osteoarthritis. He is comparing three ACP injections to three hyaluronic acid injections in patients who have painful arthritis of the knee. Before the injections, he draws out fluid from the joint to examine proteins related to cartilage breakdown and production. Gathering this data will help him determine if surgeons can use biologic markers to predict clinical outcomes.
Where the industry is headed
Studies on biologic solutions for cartilage regeneration associated with joint repair are increasingly prevalent as more orthobiologic companies push their way into the biologics market. In some cases, there are treatments approved for one indication and the surgeon researchers are working on proving them for additional indications as well.Although biologic solutions aren't always the golden ticket to pain relief, the media, lay press are patients pushing these types of solutions which gives the public a positive perception of their impact. Professional athletes have also contributed to this perception because they were the first people to seek out these treatments, oftentimes with positive results for their overall performance.
"Some solutions, such as PRP, are easy to use, but you have to prove they work," says Dr. Cole. "Unproven solutions often have an extra cost associated with them since they aren't covered by insurance companies and that can be inconvenient for the patient. We need to prove these solutions in a more reliable way. One must never forget that in some studies, a 30 percent placebo effect exists which can be mistakenly believed to be due to the treatment itself."
Learn more about Dr. Brian Cole.
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