Emerging Advances With Cartilage Replacement Techniques

J. George DeVries, DPM, and Christopher F. Hyer, DPM, FACFAS

When it comes to cartilage replacement, various promising technologies are now available to foot and ankle surgeons. These authors review the literature on osteochondral lesions of the talus and share their insights on a variety of emerging modalities ranging from fresh osteochondral allografts and autologous chondrocyte implantation to minced cartilage and bone marrow aspirate.

   Cartilage degeneration or damage in the foot and ankle is a difficult problem for both the patient and physician. Foot and ankle physicians commonly encounter degenerative joint disease, which may be due to biomechanical deficiencies, trauma, rheumatologic disease or a host of other causes.

   Isolated damage to cartilage with or without damage to the surrounding bone most often occurs as a result of trauma. Cartilage damage in the foot has undergone the most extensive study in the talar dome. The study of osteochondral defects (OCD), specifically osteochondral lesions of the talus (OLT), is a very exciting topic in foot and ankle literature with many new evolving technologies.

   Berndt and Harty most notably described OLT in their landmark study.1 Their grading scheme has the following four stages.

   • Stage 1 is a contusion to the cartilage and underlying bone without visible damage to the cartilage. This is often visible on magnetic resonance imaging (MRI) after low energy ankle trauma and may be the cause of lingering pain.
   • Stage 2 involves a partial detachment of the diseased cartilage. A section of cartilage may be flapped up but is generally still in position and stable.
   • Stage 3 involves a full thickness detachment of the cartilage with or without bone attached. This can be relatively stable or unstable, depending on the location and size of the defect.
   • Stage 4 is a full thickness lesion with or without bony attachment that is displaced or inverted.

   Canale and Belding described OLT as well and found similar findings to Berndt and Harty.2 Scranton and McDermott later described a Stage 5 lesion that involved intact cartilage with a large bony cyst underlying the joint surface.3 This type of lesion occurs more frequently on the medial talar dome and may eventually erode the overlying cartilage.

   The lesions of the talus correspond to the mechanism of injury in both location and morphology. Classically, lesions most often occur through a dorsiflexion-inversion injury or a plantarflexion-inversion injury. Those lesions that happened with the foot dorsiflexed tended to be anterolateral on the talar dome and had a more shallow or wafer shape.

   Plantarflexion injuries tended to be more posterior and medial. The lesions with these injuries had a deeper, cup-shaped presentation. When looking at the incidence of these two modes of injury pattern, the medial-based lesions occurred in about 60 percent of injuries and the lateral-based lesions occurred in 40 percent of injuries.

   All of this historic knowledge has recently undergone re-examination. In a MRI study by Raikin and colleagues, both medial and lateral lesions tended to be in the center of the talar dome as opposed to the aforementioned anterolateral and posterior central descriptions.4

A Guide To Treatment Options For Osteochondral Lesions Of The Talus

   Studies have described many treatments for OLT. Conservative treatment consisting of immobilization can be effective in stage 1, 2 and medial stage 3 lesions.2 Steroid injections can provide temporary pain relief. As the disease progresses or conservative measures fail, surgical intervention may be required.

   Arthroscopic debridement is the mainstay of early surgical care.5,6 By performing an arthroscopic synovectomy, the surgeon can visualize and address the cartilage lesion. Identify and curette any loose cartilage. Then inspect the underlying bone and resect any cystic bone. Proceed to stimulate bleeding in the underlying bone, which one can do with microfracture or antegrade percutaneous drilling.7,8 Either of these techniques allows blood to flow through the perforations in the subchondral bone. This blood forms a clot and eventually organizes into a type of fibrocartilage, which fills the hyaline cartilage deficit.

   If the overlying cartilage is intact with a large underlying cystic defect (stage 5 lesion), the surgeon can perform guided retrograde drilling to resect the cystic bone and backfill the area to allow for solid bony consolidation without disruption of the cartilage.9 Use a targeted drill guide and evacuation system to locate and treat these lesions.

   Arthroscopic techniques offer good functional outcomes with minimal surgical intervention. Failures of these interventions or lesions larger than approximately 1.5 cm require other methods. This is the area of treatment where new techniques are emerging and succeeding.

   Joint destructive techniques can be effective for these lesions. Ankle arthrodesis allows for consistent pain relief but the loss of motion leads to loss of function and increased stress on adjacent joints.10 Total ankle replacement is an option but is not desirable in younger or active patients.11 These options are certainly viable but preserving or restoring the natural joint appears to be the emphasis of much of the recent literature.

What You Should Know About Autografts And Allografts

   Osteochondral autografts have been in use for many years for osteochondral defects in various joints. This entails removing a cylinder of diseased cartilage and underlying bone, and replacing it with an osteochondral graft from elsewhere in the body. The surgeon can perform this by grafting in a single osteochondral cylinder via the osteoarticular transfer system (OATS) technique or by grafting in multiple smaller osteochondral plugs in a method called mosaicplasty. Researchers have described this extensively for OCDs in the knee with some excellent results.12-14

   Surgeons typically perform the OATS and mosiacplasty techniques in the talus by replacing the defect with an autograft taken from the patient’s knee. Studies have reported excellent results with this application as well.3,15

   Critics of this method have highlighted several aspects of the techniques as potential negatives. The harvest of the osteochondral graft requires violation of the healthy knee joint and iatrogenic damage to femoral cartilage. The cartilage in the knee has a different thickness and curvature than that in the talus, and a perfect anatomic replacement is not possible.

A Closer Look At Fresh Osteochondral Allografts

   There are several emerging concepts in cartilage replacement that are currently undergoing exploration. These include fresh osteochondral allograft (either mosaicplasty or with bulk replacement), autologous chondrocyte implantation, minced cartilage onlay, bone marrow aspirate application and new mesenchymal chondrocyte technology.

   Fresh osteochondral allograft is an exciting concept in the talus. The idea is to replace the diseased cartilage and underlying bone with a fresh and viable cartilage (similar to OATS or mosaicplasty). However, one would use a fresh osteochondral allograft replacement instead of autograft.

There are several benefits to this technique with fresh allograft. These benefits include:

   • avoidance of autograft harvest morbidity;
   • the ability to obtain size- and side-matched donor tissue to replace the host anatomy very closely; and
   • the transplantation of true hyaline cartilage, which matches the demands of the talus.

   There are several concerns with the fresh allograft option as well. First and foremost is the question of chondrocyte viability. Authors have explored the process of freezing an allograft to extend its use and shelf time, and have shown that this results in a serious decrease in chondrocyte viability.16,17 That is the impetus behind using fresh allograft stored at 2 to 4ºC as this can preserve chondrocyte viability.

   The exact timing is a little controversial. Bench studies have shown that after 14 days of preservation, viability and mechanical properties drop precipitously.18 Animal studies have shown there is a significant difference in postoperative degenerative changes between fresh osteochondral allograft implant before or after 21 days of preservation.19 Human studies in the knee have demonstrated successful implantation of fresh osteochondral allograft as long as 42 days after harvest.20

   The issue of timing between harvest of the allograft and implantation is crucially important because of the process of securing a donor specimen. Surgeons should identify patients who are appropriate for this procedure and educate them on it. Take magnification controlled anteroposterior and lateral radiographs. Physicians can subsequently submit them to either a tissue bank specializing in this type of graft or companies like Arthrex that will facilitate the matching process.

   The prospective donor is ideally under 40 years old and is free of any degenerative changes in the ankle. After the donor is found, the specimen must go through a rigorous screening process. This process evaluates for a number of potentially infectious processes, according to the American Association of Tissue Banks, and generally takes a minimum of seven days.

   The patient and surgeon must then be able to quickly move to tissue implantation. The timing from patient selection to surgical implantation ranges between six and 20 weeks at our institution. This can occasionally be further complicated by patient scheduling conflicts and availability of the donor.

   Orthopedic surgeons have used fresh osteochondral allograft in the knee for many years with one study demonstrating graft survival at 20 years of 66 percent.21 In the ankle, the use of this type of graft has ranged from replacement of small osteochondral defects via plugs all the way to complete bipolar replacement of the talar and tibial side of arthritic ankles.22,23

   Two recently published studies have looked at bulk fresh osteochondral allografts for the treatment of large talar lesions. Raikin demonstrated excellent and good results in 11 of 15 patients who were followed a minimum of two years from surgery. The researchers reported only two failures in the follow-up period.24 Hyer and colleagues presented two-year data on 17 patients and showed a 94.1 percent success rate.25 This technique is a viable option.

Can Autologous Chondrocyte Implantation Have An Impact?

   Giannini and colleagues discussed the use of autologous chondrocyte implantation (ACI) for treatment of the talus in 2001.26 This concept involves taking the patient’s own chondrocytes, expanding and growing them in a lab, and subsequently re-implanting them into the patient’s defect.

   There are several benefits of this procedure, including the use of autograft, which intuitively is most preferable. There is minimal donor site morbidity as one only needs to harvest 200 to 300 mg of host cartilage, which can even come from the detached osteochondral talar lesion.27 This essentially negates the need for an additional harvest surgery.

   After the cells are harvested, they are isolated, cleaned, cultured and expanded. The cell culture medium is changed approximately every three to four days until implantation. The timing to implantation offers flexibility and can be anywhere from around one to six months post-harvest. The cartilage repair tissue appears to be a hyaline-like repair tissue and several studies have demonstrated this repair with biopsy post-implantation.26,28 However, there is conflicting data demonstrating that rather than being hyaline-like, cartilage repair tissue is fibrocartilage, which is the same repair tissue as with microfracture.29,30

   One potential limitation of this technique is the replacement of cartilage only, which could make it less useful in those lesions with underlying cystic bone. This obstacle appears to have been overcome with the so-called “sandwich” technique, which researchers have demonstrated in both the knee and the talus.31,32

   One would perform this technique through an open ankle arthrotomy with or without a malleolar osteotomy. After identifying the talar defect, remove the cartilage defect and curette any cystic bone from the talar bone. Then fill the defect with bone graft up to the native subchondral bone. Then lay a graft of periosteum over the graft bone and attach it with a suture and/or fibrin glue. Secure a second periosteal layer over this.

   Inject the ACI medium between the periosteal grafts. The use of a matrix or scaffold can permit the surgeon to seed the chondrocytes directly onto this medium and adhere the medium directly to the defect, thereby avoiding the tedious process of periosteal graft harvesting and securing.33,34 Disadvantages of this technique include the need for at least two surgeries and the high cost of the ACI process itself.

How ACI Stacks Up To Other Techniques: What The Literature Reveals

   Several studies have compared the various cartilage techniques. Giannini and colleagues compared the results of autogenous osteochondral transplant to those of ACI. The authors concluded that both are preferable to microfracture surgery in that a hyaline or hyaline-like cartilage replaces the defect but the authors prefer ACI due to the lower donor site morbidity.35

   A level 1, prospective, randomized, controlled trial by Gobbi and colleagues compared chondroplasty to microfracture surgery and autogenous osteochondral transplant. They found no significant differences in the results.36

   In a systemic review of the literature involving 11 studies and 730 athletic patients with cartilage defects of the knee, Harris and colleagues compared microfracture surgery to ACI to OATS.37 The authors found that better clinical outcomes occurred with ACI or OATS over microfracture surgery, and microfracture surgery results deteriorated over time. Microfracture surgery was also worse with larger lesions and patients had a lower rate of return to sports. Return to pre-injury level of sports was the fastest with OATS and the slowest with ACI.

Pertinent Insights On Minced Cartilage

   Minced cartilage is a very new and exciting concept. Research has shown that one can harvest autologous cartilage, mince it into very small pieces and implant the pieces into cartilage defects. The cartilage particles are a rich source for chondrocyte redistribution and are capable of forming hyaline-like cartilage.38 This process essentially allows for the expansion of the available area of coverage without having to sacrifice a large donor area and without the time delay and cost associated with ACI.

   The DeNovo NT (Zimmer) is a new product that uses juvenile minced cartilage to act as an allograft source to this tissue. There are intriguing benefits with an available supply of robust, healthy cartilage and no donor site. The product currently takes some time to get and has a limited shelf life. However, it may be an allogenic alternative to ACI.39

   Bear in mind that this process of employing minced cartilage is solely focused on cartilage replacement. Accordingly, one would not be able to manage subchondral cystic formation with this modality. No research or publications have evaluated a “sandwich” technique for this technology.

What Are The Merits Of Bone Marrow Aspirate?

   Another recently introduced concept is that of bone marrow aspirate implantation. The technique entails removing bone marrow aspirate from the iliac crest and concentrating it. The concentrated cells are then applied into either a collagen powder or a hyaluronic acid membrane, and mixed with a platelet-rich fibrin gel.

   Using an arthroscopic approach, one would debride the talar OCD. Then evacuate the ankle joint of fluid and achieve hemostasis at the subchondral bone interface. Proceed to introduce bone marrow aspirate on a scaffold into the ankle and inlay the scaffold into the defect. Secure the area with the fibrin gel and run the ankle through range of motion to ensure stability.

   Giannini and colleagues examined this technique as a quicker and less costly alternative to ACI.40 In a prospective study, the researchers followed 48 patients for a minimum of two years after this type of procedure. Pre-clinical laboratory data confirmed the osteogenic and chondrogenic properties of the bone marrow aspirate. Results were very positive with increasing American Orthopedic Foot and Ankle Society (AOFAS) scores.

   In addition, the study showed 94 percent of patients returning to low impact sports at approximately four months and 77 percent of patients returning to high-impact sports at around 11 months. The cartilage also appeared to compare favorably to ACI repair with a hyaline-like cartilage repair.

   This is an exciting concept. Further studies will need to evaluate the long-term outcomes of this technique, which may offer a quicker and more cost-effective alternative to ACI.

What About The Potential Of Stem Cell Therapies?

   Finally, researchers have discussed the role of cell therapy and mesenchymal stem cells. Several researchers have shown the ability to harvest and proliferate multi-potent stem cells from tissue samples taken from the synovial membrane of adults. One can direct these cells into various tissue types, including chondrocytes. These findings have prompted researchers to propose this technology as a potential way to treat various skeletal pathologies, including cartilage defects.41,42

   To the best of our knowledge, there are no clinical studies or products available that utilize this technology. However, cell therapy and the use of these mesenchymal stem cells may offer options in the future for many applications in orthopedics and beyond.

In Conclusion

   Currently, the gold standard treatment for articular cartilage defects in the talar dome is debatable. There is a significant history of treatment with microfracture surgery or autologous osteochondral transplant, but both have significant drawbacks.

   While there is still no consensus on the ideal way to treat this difficult pathology, numerous emerging technologies are at various stages of development and research. Currently, repair of damaged cartilage is a very exciting topic with significant developments for the future treatment of this problem.

Dr. DeVries is an Associate of the American College of Foot and Ankle Surgeons. He is a Fellow with the Advanced Foot and Ankle Reconstruction Fellowship at the Orthopedic Foot and Ankle Center in Westerville, Ohio.

Dr. Hyer is a Fellow of the American College of Foot and Ankle Surgeons. He is the Director of the Advanced Foot and Ankle Reconstruction Fellowship at the Orthopedic Foot and Ankle Center in Westerville, Ohio.


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