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Autologous Chondrocyte Implantation in the Talus

Indications

Autologeous chondrocyte implantation (ACI) is one of several surgical treatment options for symptomatic cartilage defects. ACI is best suited for patients between 18 and 50 years of age. ACI is indicated for management of symptomatic osteochondral lesions failing debridement, drilling, or microfracture.   Primary ACI can be considered in lesions larger than 2 cm² or in osteochondral lesions defects (OCD) associated with expansive subchondral cysts (Stage V lesion).

Advantages of ACI include the following:

  • ACI provides a stable cartilage rim that can be maintained at the site of the lesion.
  • Large defects can be readily addressed with this technique.
  • With matrix-based chondrocytes, shoulder lesions can be managed.

Disadvantages of the ACI for the talar dome are.

  • ACI has Food and Drug Administration (FDA) approval only for the knee (as of April 2011).
  • The cost from industry for chondrocyte culture is considerable.
  • The procedure requires two stages to allow time for chondrocyte culture.

Reports of the traditional technique that requires a periosteal flap under which the transplanted chondrocytes are positioned suggest limitations of the technique for the talus. Many OCDs involve, at least in part, the talar shoulder, an anatomic region poorly suited for anatomic coverage with a periosteal flap. The advantages of matrix-based autologous chondrocyte transplantation (eg, MACI™), meanwhile, have completely extruded the former techniques, which required coverage of the defect with a periosteal flap. Histological investigations have shown that matrix-based chondrocyte transplantation may offer an improved alternative to traditional treatments for cartilage injury by regenerating hyaline-like cartilage.

Informed consent and patient education are imperative for ACI. ACI for the ankle lacks FDA approval. However, for larger OCDs or OCDs failing prior surgical management, ACI provides patients and their surgeons a potentially successful treatment avenue that did not exist prior to ACI. Early favourable outcomes with ACI applied to difficult OCDs justify the extra effort, education, and communication among physicians, patients, and third-party payers that may be required to proceed with ACI in the ankle.

Harvesting cells for culturing is considered to be part of a drug-producing process. Therefore, special permission has to be requested by the local health care administration. Standard operating procedures (SOPs) for harvesting and transportation of the cartilage cells are mandatory for the accreditation process.

Preoperative Planning

All imaging studies are reviewed, with MRI providing detail of the cartilage defect and CT providing detail of subchondral bone involvement.

  • Pure cartilage defects or shallow OCDs can be managed with the conventional ACI procedure; deeper OCDs require a “sandwich technique.”
  • The “sandwich technique” involves two layers of collagen membranes with chondrocytes. The defect is prepared and bone grafted to recreate the subchondral bone architecture. 
  • Within the last few years, matrix-basesd ACI has gained increasing popularity. Different scaffolds are offered by the industry (based on collagen or hyaluronic acid). Matrix-based chondrocytes that do not require a periosteal flap can be placed directly on a bone graft, which makes the management of Stage V lesions, as well as lesions of the talar shoulder, less demanding.

Positioning

Harvesting of Chondrocytes
  • Standard arthroscopy of the ankle.
  • Harvesting of chondrocytes can be performed with conventional knee or ankle arthroscopy. Suitable locations for harvesting expendable articular cartlilage from the knee include: peripheral superolateral medial or lateral femoral condyle or the intercondylar notch. Alternatively, Giannini et al have demonstrated that the detached OLT fragment at the time of index arthroscopic debridement/drilling or microfracture may be an acceptable source of chondrocytes for ACI. However, this result was not confirmed by Candrian et al. Other possible areas are the anterior part of the the talus.
  • Using a curette, two to three full-thickness articular grafts are harvested; the grafts include the superficial layer of subchondral bone. The grafts are transferred to a sterile container and transported to the laboratory. Using a patented procedure, the articular cartilage matrix is enzymatically disrupted to isolate the chondrocytes. Culturing of chondrocytes requires approximately 2-6 weeks, depending on the company and the preferred culturing process.
Transplantation of Chondrocytes
  • Depending on the location of the defect, the patient is positioned supine with a slightly internally or externally rotated leg. If an iliac crest graft is to be obtained, the pelvis needs to be prepped and draped as well, and the ipsilateral pelvis supported with a bump. Alternatively, the bone graft may be harvested from the calcaneus, distal tibia, or proximal tibia -- all locations within the surgical field typically prepared for ACI. A vacuum mattress can be helpful in adjusting the patient’s position during the procedure.

Approach

Harvesting chondrocytes
  • Medial and lateral anterior portals give an adequate overview of the joint and allow the harvesting of chondrocytes.
Transplantation
  • Depending the location of the OCD, a central medial approach between the anterior tibial tendon and the extensor hallucis longus tendon, a dorsomedial approach between the medial malleolus and posterior tibial tendon, a medial transmalleolar approach with osteotomy, or a lateral approach (with or without osteotomy) can be considered. ACI demands adequate exposure to properly suture a periosteal patch circumferentially around the OCD.
  • However, the membrane-based techniques hardly ever need an osteotomy. Due to the fact that a perpendicular access to the defect is not necessary, most OCDs can be accessed by a ventral approach with distraction to avoid an osteotomy. If periosteum has to be sutured to cover the defect, ACI cannot be performed properly without medial malleolar osteotomy for extensive medial OCDs and ATFL/CFL release and/or lateral malleolar osteotomy for extensive lateral OLTs.
  • A major advantage compared to Mosaique or OATS is that a perpendicular access is not required. Muir et al ? demonstrated that the majority of the talar dome can be accessed without osteotomy, but acknowledged that osteotomies are required to adequately expose extensive OCDs.

Techniques

Harvesting Cells
  • Diagnostic arthroscopy is completed and all pathology is identified.
  • Giannini et al have demonstrated that the detached OCD fragment at the time of index arthroscopy may be an acceptable source of chondrocytes in ACI.
  • Otherwise a small, full-thickness piece of cartilage can be harvested with a curette from the medial or lateral aspect of the anterior talus (Figure 1).


Figure 1. Harvesting of cartilage

  • Place the specimen in the medium, which is provided by the manufacturer handling the cultivation of the cells.
  • Ensure that the cells are sent to the company immediately, sustain the cool chain, and include the required documents in the box.
Autologous Cell Implantation

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  • To avoid the risk of compromising chondrocyte viability, use a tourniquet to maintain a bloodless field. We typically utilize a thigh tourniquet; although a calf tourniquet is possible, compression of the lower leg musculature may restrict exposure/manipulation of the ankle, thereby compromising exposure. 
  • Expose the transplantation site. Despite adequate exposure with appropriate osteotomies or ligament releases, ACI’s second stage for the ankle, in particular suturing the periosteal flap, may prove tedious. Figure 2 shows a V-shaped medial malleolar osteotomy, which has a low risk of fixation in a dislocated position in combination with a high primary stability. Matrix-based transplants, where the chondrocytes for transplantation are already grown in a collagen matrix, provide a significant advantage. These membranes can be fixed with fibrous glue; sutures are only optional. For the knee, both techniques have had similar clinical outcome. At the talus, there is still a lack of scientific evidence; however our extended anecdotal experience has shown similar results with both techniques.


Figure 2. V-shaped medial malleolar osteotomy

  • Debride all unstable cartilage with a curette, to create a healthy, stable cartilage rim. The subchondral bone in the defect should be intact. Figure 3 shows an incomplete healing after microfracture; Figure 4 a large detached fragment at the medial shoulder of the talar dome.


Figure 3. Incomplete healing after microfracture


Figure 4. Detached fragment at the medial shoulder of the talar dome

  • If a shallow bony defect exists, remove the sclerotic bone. Despite tourniquet use, some bleeding may be encountered that should be controlled with an epinephrine sponge or a minimal amount of fibrin glue. Perforate sclerotic areas by multiple drillings (Figure 5).


Figure 5. Multiple drillings to perforate sclerotic areas

  • In the event of a deeper defect, the “sandwich technique” described above should be employed to recreate subchondral support for the transplanted chondrocytes. Fill any bony cyst with autologous bone graft.
  • The graft must be impacted to provide a smooth surface for the transplantation site (Figure 6).


Figure 6. Impact the graft for a smooth transplant surface

  • Measure the defect and create a template using a small piece of paper (from a sterile glove pack) or aluminum foil (from a suture pack).
  • When matrix-based chondrocytes are being used, no further preparation is required after measuring the size of the defect. The matrix is stable and can directly be fixed to the OLT.
  • Care should be taken when removing the transplant from the transport container. Avoid squeezing the transplant.
  • Cut the transplant according to the size of the defect. Some companies provide special punches for this step. The size of the transplant should be exactly the size of the defect. A preparation 2 mm larger as recommeded for the periosteal flap can lead to overlaying edges and a lack of stability.
  • Place the transplant into the defect. A first fixation occurs through adhesion forces. The edge can than be stabilized with 6-0 sutures and fibrin glue (Figure 7).


Figure 7. Transplant placed in the defect

  • Check the transplant for stability by carefully moving the ankle joint into dorsiflexion and plantarflexion. We recommend that postoperative mobilisation be limited so that the transplant is always covered at least partially by the tibia plafond to prevent shear forces. The optimal postoperative range of motion can be checked in this step.
  • Insert on intra-articular tube prior to wound closure, and then stabilize the ankle joint with repair of the ligaments or osteotomy, depending on the approach (Figure 8).


Figure 8. Insertion of an intra-articular tube

Pearls and Pitfalls

  • Care must be taken to address associated pathology. Stabilize any instability and correct axial deformities.
  • Generalized osteoarthritis is a contraindication.
  • Cartilage damage at the corresponding tibial can compromise the results.
  • The extent of cartilaginous detachment is often underestimated in MRI, whereas the bony reaction tends to be overestimated.
  • OCDs with subchondral cysts respond poorly to drilling or microfracturing. In these cases, ACI can be considered as a primary procedure.
  • ACI is not indicated in diffuse ankle arthritis; it is intended for focal defects only.
  • Extreme care should be taken when harvesting the chondrocytes from the ankle or ipsilateral knee joint.
  • If not completely destroyed, the detached cartilage can be harvested.
  • Ensure that the cool chain for transport is appropriate.
  • Cultivation service is provided by several companies. They provide the medium for harvesting the chondrocytes and, in some cases, special tools for harvesting and transplantation.
  • Ensure that the transplant is large enough.
  • Adequate exposure is mandatory for ACI. This sometimes requires a malleolar osteotomy.
  • Intraoperative x-rays should be taken before performing an osteotomy and after the osteosynthesis. The osteotomy should be adequate to gain sufficient access to the OCD.
  • Do not squeeze the transplant.
  • Follow the rehabilitation plan; it takes its time until the graft has gained its final stability and strength. Too much, too fast is the most common reason for failures.

Postoperative Care

  • After covering the wounds with sterile dressings, stabilize the ankle joint with a dorsal splint.
  • Immediately postoperative, the patient should be on 48 hours of bed rest, the ankle should not be moved, and the ankle should be fixed with a brace.
  • 48 hours postoperative: Remove the drainage tubes and mobilize the joint with continuous passive motion. Limitations can occur in large defects or extended ligament repair.
  • During the first 6 weeks postoperative: Allow the patient partial weight bearing (10 kg) and mobilization without weight bearing, including accompanying physiotherapy (similar to the postoperative scheme in complex ankle fractures with ORIF).
  • After 6 weeks: A gradual increase in joint loading is allowed (20-30 kg every 2 weeks) up to full body weight.
  • After 12 weeks: Full weight bearing in daily life activities is allowed, including cycling with moderate resistance and swimming.
  • After 6 months: Increased sports activities, eg, jogging and skating, can be considered. However, there is little experience in bringing patients with an ACI or MACI back to professional sports. In our anecdotal experience, most patients are able to return to recreational sports.
  • The advisability of returning to contact sports and sports with high physical demands on the ankle joint is unclear. So far, no data are available.

Outcome

  • Only limited data are available on this new treatment concept, with no long-term studies.
  • Schneider  et al reported the results of 20 consecutive patients managed with MACI for the ankle.   At an average follow up of 21.1 months, they reported significant improvement in mean AOFAS ankle score, from 60 (range, 25 to 87) to 87 (range, 41 to 100) (p < 0.0001). Overall improvement in pain scores was also significant (p < 0.0001).
  • Giannini et al found an improvement, from 37.9 +/- 17.8 points to 92.7 +/- 9.9 (p < .0005), in the AOFAS ankle score, with MRI showing well-modeled restoration of the articular surface and no significant difference compared with that of healthy hyaline cartilage in a group of 10 persons after a 10-year follow up.
  • Baums found an improvement in the AOFAS ankle score, from 43.5 to 88.4, in a prospective study on 12 patients.
  • By culturing the chondrocytes from the detached chondral fragment, donor site morbidity can be avoided.   However by taking small chips of cartilage form an unloaded area of the knee, the risk of donor site problems should be significantly lower, as reported for harvesting osteochondral grafts from the ipsilateral knee joint.
  • There is still a lack of evidence on the concept of ACI at the talus.   Because of the relatively high cost of ACI and the knee morbidity seen in OATS, Zengerink et al concluded in their systematic review that the bone marrow stimulation technique is the treatment of choice for primary osteochondral talar lesions. However, due to great diversity in the articles and variability in treatment results, no definitive conclusions can be drawn. Further sufficiently powered, randomized clinical trials with uniform methodology and validated outcome measures should be initiated to compare the outcome of surgical strategies for OCD of the talus. Recent results suggest that MACI may be an effective way to treat full-thickness lesions of the talus using harvested chondrocytes from the talus in patients who do not respond to initial curettage and microfracture.   Figure  9 shows a 12-month result after an extensive OCD at the medial talar shoulder, treated with a membrane-based ACI (MACI™) in combination with local bone grafting from the calcaneus.


Figure 9. 12 months after treatment with a membrane-based ACI

Complications

  • In rare cases, the harvested chondrocytes are not suitable for culture. Typical causes are avital cells or contamination. In this case, the physician is informed by the laboratory, which cultures the cartilage cells. One possiblity is to do another arthroscopy to get cartilage cells; however other treatment options such as OATS can be considered.
  • Delayed union in the malleolar osteotomy is possible. Provided progression toward healing, even if very gradual, is observed on serial radiographs, our experience has been that the osteotomies eventually heal without complications. However, prompt revision open reduction and internal fixation with bone grafting is warranted if no progression toward healing is noted. This limits the risk of displacement of the osteotomy.
  • Failure of the transplanted tissue, which includes detachment of the transplant, delamination, hypertrophy, or ossification, may occur. Especially in the periostal flap technique, ossifications are a common cause of failure.   Local tissue hypertrophy can cause ankle impingement.
  • Resorption of the subchondral bone graft in stage V lesions that were treated in the sandwich technique can lead to a graft failure.
  • The source of pain from an OCD remains ill-defined, and the success of cartilage resurfacing procedures is certainly not 100%. Therefore, even without obvious complication, pain may persist.
  • If the clinical outcome is not satisfactory and follow-up imaging studies are suggestive of graft compromise, ankle arthroscopy is warranted. While failure of graft incorporation or delamination of the resurfaced articular segment is perhaps irreversible, not all persistent symptoms are necessarily due to such phenomena. Fibrous tissue may form at the graft-host articular junction or within the ankle, causing impingement. This can be effectively debrided by arthroscopy to relieve symptoms. ACI in particular is subject to fibrillation or hypertrophy and arthroscopic debridement, in select cases, is essential to removal mechanical symptoms and avoid delamination of the graft.  Second-look arthroscopy may demonstrate that the cartilage resurfacing procedure was successful but was inadequate to resurface what proved to be a larger area of diseased talus than originally identified.
  • In ACI for which the cartilage cells are harvested from the knee, there is a risk for persistent knee symptoms. We always harvest chondrocytes from the ankle joint to minimize the risk for donor site problems. According to our extended anecdotal experience in doing so, we have seen no disadvantage with this concept.
  • General surgical complications like deep venous thrombosis, wound healing problems, or infection can occur.

References

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