Autologous Matrix-Induced Chondrogenesis for Osteochondral Lesions of the Talus

Introduction

Autologous matrix-induced chondrogenesis (AMIC) is one of several surgical treatment options for symptomatic cartilage defects. AMIC combines microfracture surgery with the application of a bi-layer porcine collagen I/III matrix (Chondro-Gide®, Geistlich Pharma AG, Switzerland) with the goal of stabilizing the superclot in the defect area to promote the formation of fibrous cartilage.

The AMIC technique evolved with the aim to improve some of the shortfalls of microfracture surgery, for example, variable repair cartilage volume and functional deterioration over time.^1,2 In addition, AMIC was intended to provide a simple technique for securely retaining the fragile blood clot in larger defects with the collagen matrix and to possibly enhance the chondrogenesis of mesenchymal stem cell.^3,4 Mid-term good clinical outcomes have been shown using the AMIC technique to treat chondral lesions in the knee joint, with results similar to those reported after autologous chondrocyte implantation (ACI) technique.^5-9

This article describes the use of the AMIC technique in large osteochondral lesions (OCL) of the talus.

Indications

AMIC in the talus is best suited for patients between the ages of 18 and 50 years, with symptomatic OCLs of more than 1.5 cm² and 0.5 cm depth or with OCLs associated with expansive subchondral cysts (ICRS Stage III and IV lesions). It is also a treatment option for full-thickness cartilage defects caused by a variety of conditions other than OCL, such as ankle fracture management (Figure 1).

Figure 1. Ankle fracture

This technique is suitable for primary treatment of larger defects as well as for therapy after failed previous surgery, including debridement, drilling, or microfracture. Axial malalignment or instability must be addressed during the surgery. Appropriate patient selection by the treating physician followed by thorough patient information and education is imperative and a prerequisite for good outcome.

Advantages of AMIC:

Minimally invasive, one-step surgical technique for the treatment of chondral and osteochondral lesions
In most cases, can be performed using a minimal arthrotomy without an osteotomy of the medial or lateral malleolus
Off-the-shelf availability of Chondro-Gide® membrane
Easy handling, fixation with fibrin glue¹⁰
Chondro-Gide® positively influences chondrogenic differentiation of mesenchymal stem cells and stimulates chondrocytes to enhance proteoglycan deposition^3,4,11
No donor site morbidity and no culturing of chondrocytes in vitro when compared with ACI
Chondro-Gide® CE-certified for use in Europe

Disadvantages of AMIC:

Not approved by the U.S. Food and Drug Administration
Lack of extensive clinical data

Preoperative Planning

Clinical Findings

Clinical findings are often unspecific pain at the ankle, aggravated by loading or sports. The final diagnosis is made by MRI. However, other pathologies that may promote cartilage damage in the joint, such as ankle instability or malalignment, should be investigated and addressed either before performing AMIC or as a one-step procedure.

Diagnostic Imaging

Radiographic imaging and magnetic resonance imaging (MRI) are essential diagnostic tools.
Conventional standing radiography in two planes is performed to assess skeletal deformations. Depending on the projection, an existing OCL is commonly not observable on plain X-ray.
The MRI examination assists in showing the chondral or osteochondral defect and in diagnosing attendant soft-tissue pathologies (Figure 2). The extent of the lesion can be overestimated in the MRI when there is attendant osseous oedema.
Optional CT shows the size of the osseous lesion with more precision than MRI.

Figure 2. MRI of osteochondral lesion

Positioning

Depending on the location of the defect, the patient is positioned supine with a slightly internally or externally rotated leg.
For a dorsolateral approach, the patient is positioned on the contralateral side; for a dorsomedial approach, on the ipsilateral side.
A bone graft may be harvested from the calcaneus, distal tibia, or proximal tibia, depending on the quantity of graft needed. In our experience, a bone graft from the calcaneus is sufficient in most cases.
General or regional anesthesia may be utilized.
Tourniquet use is recommended to have a dry surface while using the fibrin glue to fix the membrane to the bone.

Approach

Depending on the location of the OCL, different miniarthotomies can be used to provide good access to the defect without the need for an osteotomy.

Medial defect: A ventromedial approach medial of the anterior tibial tendon with maximum plantar flexion allows the surgeon to reach even very dorsally located OCLs (Figure 3).

Figure 3. Ventromedial approach

Central defect: A central ventral approach between the anterior tibial tendon and the extensor hallucis longus tendon gives good access to the entire joint. This approach has advantages if the medial and lateral edge of the talar dome have to be addressed or in cases with isolated central defects (Figure 4).

Figure 4. Central approach

Lateral defect: Traumatic lesions of the ventrolateral talus can be reached well via the ventrolateral approach lateral of the peroaeus terzius tendon (Ollier approach) (Figure 5).

Figure 5. Ventrolateral approach

Dorsomedial defect: If it is not possible to address a medial defect with the ventromedial approach, a dorsomedial approach between the medial malleolus and posterior tibial tendon can be used. The patient must be positioned on the ipsilateral side for this approach (Figure 6).

Figure 6. Dorsomedial approach

Dorsolateral defect: A dorsolateral approach between lateral malleolus and peroneal tendons gives access to the very dorsal located defects on the lateral side. The patient has to be positioned on the contralateral side (Figure 7).

Figure 7. Dorsolateral approach

An additional osteotomy of the medial or lateral malleolus is rarely needed when using one of the five approaches described above.^12,13

Technique

Diagnostic Arthroscopy

Initial diagnostic arthroscopy can be performed, but is not mandatory, before the mini open surgery. Arthroscopy can be used to assess ligament instability and to locate and determine the size of the OCL. A standard 2.7-mm arthroscope with a 30-degree lens and isotonic electrolyte solution as the arthroscopy medium is recommended.

Most OCLs (even dorsomedial defects) can be accessed by a ventral approach with distraction to avoid an osteotomy. The approach is chosen according to the location of the defect. The access to the joint can be facilitated using a K-wire spreader (Figure 8). One K-wire is placed in the talus, the other in the tibia. With the K-wire spreader, the joint than can easily be distracted. The use of 2.0-mm K-wires is recommended to avoid deformation during distraction.

Figure 8. K-wire spreader

Damaged and unstable cartilage and necrotic bone beneath the chondral defect are removed using a scalpel and curettes. Any osseous cysts are curetted and the mucoid content is completely removed. The cartilage edges of the healthy cartilage must be stable and upright (Figure 9).

Figure 9. Debridement of the chondral defect

The sclerotic area at the base of the lesion is perforated (microfractured) using a sharp awl from the periphery of the lesion towards the center at intervals of 2 to 4 mm. The residual tissue is carefully removed and adequacy of the subchondral bleeding is verified. The perforation of the sclerotic area can be performed by way of antegrade drilling with adequate cooling (Figure 10).

Figure 10. Sclerotic area perforated by an antegrade drill

The osseous defect is reconstructed up to the subchondral bone lamella using autologous bone from the proximal tibia, the calcaneus, or the iliac crest, depending on the amount of graft needed. To reduce the quantity of graft needed, bone substitutes can be used. Care has to be taken that the graft does not top the level of the surrounding bone level. In most cases, bone graft from the calcaneus is sufficient (Figure 11)

Figure 11. Bone graft from the calcaneus may be sufficient

An exact impression of the defect is made using a sterile aluminum template, which is transferred to the matrix and the matrix is cut to shape. Because of the precision required in the ankle joint, it is recommended that the Chondro-Gide® matrix be trimmed in a moistened condition, as the material will increase in size by approximately 10% - 15% after moistening (Figure 12).

Figure 12. Chondro-Gide® matrix must be precisely sized for the ankle

Commercially available fibrin glue (Tissucol, Baxter) is applied directly to the bone to seal the graft. The matrix is then glued in with the porous surface facing the bone (Figure 13). After the glue is set (approximately 3 minutes), the stable position of the matrix is checked by moving the joint 10 times between plantar extension and dorsal flexion. To avoid delamination, care should be taken that the matrix does not overlap the edge of the adjacent cartilage. Investigate the reason for reasons for delamination if it occurs. If the matrix is oversized, it has to be cut to the appropriate size and reglued to the defect. If the graft in the defect exceeds the level of the subchondral bone, it has to be reduced to a level slightly below the original cortical bone.

Figure 13. Defect is covered with the graft, which is sealed with fibrin glue

After treating the OCL, the joint is closed. A drain without suction can be used if needed. It is recommended that associated pathobiomechanical factors be corrected subsequent to the AMIC procedure. For chronic instability, this includes reconstruction of the ligaments (medial, lateral or combined); for axial malalignment, corrective osteotomy (supramalleolar, talar or calcanear).

Pearls and Pitfalls

Address associated pathologies, such as instabilities, and correct axial deformities.
Generalized osteoarthritis and diffuse ankle arthritis are contraindications to AMIC.
OCLs with subchondral cysts respond poorly to drilling or microfracturing. In these cases, AMIC can be considered as a primary procedure.¹⁴
Normally, the AMIC procedure can be done by distracting the joint with a K-wire spreader. Malleolar osteotomy can be avoided in most cases.
Intraoperative X-rays are necessary only when performing an osteotomy. In those cases, X-rays should be taken before performing an osteotomy and after the osteosynthesis. If an osteotomy is done, it should be adequate to gain sufficient access to the OCL.
Follow the rehabilitation plan; it takes time until the graft has gained final stability and strength. Too much, too fast, too soon may lead to graft failure.

Postoperative Care

It is recommended that the patient receives thrombosis prophylaxis with low molecular weight heparin until he/she is more than 50% weight-bearing and ankle movement is allowed. Non-steroidal anti-rheumatic drugs can be administered as analgesics. Sufficient elevation and cryotherapy are important. Additional physical therapy (muscle stimulation or electrotherapy) may be used for postoperative treatment as required.
Postoperatively, the ankle is immobilized for 48 hours in a splint. After that, the drain is removed and continuous passive motion (CPM) is started to promote cartilage healing.
If the surgery was limited to cartilage reconstruction without additional procedures such as osteotomies, partial weight-bearing with 10 kg and CPM is allowed for the first 6 weeks. The range of motion is limited to 20 degrees plantar flexion and dorsiflexion. The usage of the splint is limited to 2 weeks to secure soft tissue healing. In the case of additional procedures, a more strict postoperative protection might be mandatory.
Physiotherapy includes isometric muscle activation and closed kinetic chain exercises to strengthen and stabilize the ankle joint and the lower leg muscles. The increased load brings about an adaptive inflammation phase in which patients often report an initial increase in the level of pain.
After 6 weeks, a gradual increase in joint loading is allowed (maximum 20 kg every 2 weeks) up to full body weight. Light sports activities (cycling, swimming) can be introduced between 3 and 6 months. The ability to engage in a complete range of sports is achieved after 6 months at the earliest; for high-impact sports, this can be up to 12 months. Transition to the next load stage should only be made if the previous stage has been managed without problems.
There is little experience in bringing patients with an ACI or AMIC back to professional sports. However, in our 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; thus far, no data are available. If the patient feels, that he/she wants to return to high impact sports, we recommend waiting for at least 12 months.

Outcome

Only limited data are available on the use of the AMIC technique in the talus, with no long-term studies available at present. Basic research could demonstrate that the use of a collagen membrane improves the stabilization of the superclot after microfracture, compared with microfracture alone.

Wiewiorski et al reported the reconstruction of a large focal OCL of the talus with the AMIC technique.¹⁵ They found that the AOFAS hindfoot score increased to the maximum of 100 points at 1 year following the procedure. The talus showed full osseous consolidation and a nearly anatomic shape of the medial talar edge. The patient was free of pain (VAS 0) during sport activities, and returned to jogging twice a week.

We recently evaluated our first 20 patients with more than 30 months of follow up. The average AOFAS score improved significantly from 48 to 88 points. There was no significant difference in the leg circumference and in the range of motion between the treated and the untreated ankle, which seems to be an indicator of normal leg function.

Further sufficiently powered, randomized clinical trials with uniform methodology and validated outcome measures should be initiated to compare the outcome of surgical strategies for OCL of the talus. Recent results suggest that AMIC may be an effective way to treat full-thickness lesions of the talus without harvesting chondrocytes from the talus in patients who do not respond to initial curettage.

Complications

Progression toward healing, observed on serial radiographs, is very gradual. Our experience has been that the osteotomies eventually heal without complications. However, prompt revision, open reduction, and internal fixation with bone grafting are warranted if no progression toward healing is noted.
Pain is regularly encountered during the beginning of full weight-bearing and physical therapy after immobilization. The source of pain from an OCL remains ill-defined, and cartilage resurfacing is certainly not 100%. 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. 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. 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.¹⁶
General surgical complications such as deep venous thrombosis, wound healing problems, or infection can occur.

References

Choi WJ, Park KKm Kim BS, Lee JW. Osteochondral lesion of the talus: is there a critical defect size for poor outcome? Am J Sports Med. 2009 Oct;37(10):1974-80. Epub 2009 Aug 4.
Chuckpaiwong B, Berkson EM, Theodore GH. Microfracture for osteochondral lesions of the ankle: outcome analysis and outcome predictors of 105 cases. Arthroscopy. 2008 Jan;24(1):106-12. Epub 2007 Nov 19.
Dickhut A, Dexheimer V, Martin K, Lauinger R, Heisel C, Richter W. Chondrogenesis of human mesenchymal stem cells by local transforming growth factor-beta delivery in a biphasic resorbable carrier. Tissue Eng Part A. 2010 Feb;16(2):453-64.
Fuss M, Ehlers EM, Russlies M, Rohwedel J, Behrens P. Characteristics of human chondrocytes, osteoblasts and fibroblasts seeded onto a type I/III collagen sponge under different culture conditions. A light, scanning and transmission electron microscopy study. Ann Anat. 2000 Jul;182(4):303-10.
Steinwachs MR, Guggi T, Kreuz PC. Marrow stimulation techniques. Injury. 2008 Apr;39 Suppl 1:S26-31.
Kusano T, Jakob RP, Gautier E, Magnussen RA, Hoogewoud H, Jacobi M. Treatment of isolated chondral and osteochondral defects in the knee by autologous matrix-induced chondrogenesis (AMIC). Knee Surg Sprts Traumatol Arthrosc. 2011 Dec 25. [Epub ahead of print]
Schiavone Panni A, Cerciello S, Vasso M. The manangement of knee cartilage defects with modified amic technique: preliminary results. Int J Immunopathol Pharmacol. 2011 Jan-Mar;24(1 Suppl 2):149-52.
Gigante A, Calcagno S, Cecconi S, Ramazzotti D, Manzotti S, Enea D. Use of collagen scaffold and autologous bone marrow concentrate as a one-step cartilage repair in the knee: histological results of second-look biopsies at 1 year follow-up.
Gille J, Schuseil E, Wimmer J, Gellissen J, Schulz AP, Behrens P. Mid-term results of Autologous Matrix-Induced Chondrogenesis for treatment of focal cartilage defects in the knee. Knee Surg Sports Traumatol Arthrosc. 2010 Nov;18(11):1456-64. Epub 2010 Feb 2.
Neumann K, Dehne T, Endres M, Erggelet C, Kaps C, Ringe J, Sittinger M. Chondrogenic differentiation capacity of human mesenchymal progenitor cells derived from subchondral cortico-spongious bone. J Orthop Res. 2008 Nov;26(11):1449-56.
Young KW, Deland JT, Lee KT, Lee YK. Medial approaches to osteochondral lesion of the talus without medial malleolar osteotomy. Knee Surg Sports Traumatol Arthrosc. 2010 May;18(5):634-7. Epub 2009 Dec 18.
Navid DO, Myerson MS. Approach alternatives for treatment of osteochondral lesions of the talus. Foot Ankle Clin. 2002 Sep;7(3):635-49.
Robinson DE, Winson IG, Harries WJ, Kelly AJ. Arthroscopic treatment of osteochondral lesions of the talus. J Bone Joint Surg Br. 2003 Sep;85(7):989-93.
Wiewiorski M, Leumann A, Buettner O, Pagenstert G, Horisberger M, Valderrabano V. Autologous matrix-induced chondrogenesis aided reconstruction of a large focal osteochondral lesion of the talus. Arch Orthop Trauma Surg. 2011 Mar;131(3):293-6. Epub 2010 Jan 21.
Schneider TE, Karaikudi S. Matrix-Induced Autologous Chondrocyte Implantation (MACI) grafting for osteochondral lesions of the talus. Foot Ankle Int. 2009 Sep;30(9):810-4.