Autologous Chondrocyte Transplantation

DEFINITION

There are several reasons for cartilaginous defects of the ankle: Traumatic injury

Osteochondritis dissecans (OCD)

Degenerative changes

The necessity to treat a cartilage defect of the ankle depends on the clinical presentation. Osteochondral lesions of the talus (OLTs) are often found incidentally on screening magnetic resonance imaging (MRIs) obtained for reasons other than suspected intra-articular pathology.

Autologous chondrocyte transplantation (ACT), also known as autologous chondrocyte implantation (ACI), is one of several surgical treatment options for symptomatic cartilage defects. In my opinion, ACI is best suited for patients between 18 and 50 years of age.

ACI is indicated for management of symptomatic OLTs failing to respond to débridement, drilling, or microfracture.1,9,34

Primary ACI can be considered in lesions larger than 2 cm2 or in osteochondral lesions associated with expansive subchondral cysts (stage V lesion).57

Advantages of ACI include the following:

ACI provides a stable cartilage rim that can be maintained at the site of the OLT. Large defects can be readily addressed with this technique.

The periosteal flap can be harvested from the adjacent medial tibia.

With carefully executed suture technique or with matrixinduced chondrocytes, shoulder lesions can be managed.

Disadvantages of the ACI for the talar dome are as follows:

ACI has Food and Drug Administration (FDA) approval only for the knee. ACI at the talus as well as matrixinduced autologous chondrocyte implantation (MACI) is considered investigational (as of January 2015).

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 suggested limitations of the technique for the talus.54 Many OLTs involve, at least in part, the talar shoulder, an anatomic region poorly suited for anatomic coverage with a periosteal flap. Recently introduced MACI may afford advantages because it does not require coverage of the defect with a periosteal flap. Histologic investigations have shown that MACI may offer an improved

alternative to traditional treatments for cartilage injury by regenerating hyaline-like cartilage.57 Informed consent and patient education are imperative for ACI. ACI for the ankle lacks FDA approval.

However, for larger OLTs, OLTs failing to respond to prior surgical management, or OLT with

subchondral cysts, ACI provides patients and their surgeons with a potentially successful treatment avenue that did not exist before ACI. Early favorable outcomes with ACI applied to difficult OLTs 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.

In Europe, harvesting cells for culturing is considered part of a drug-producing process. Therefore, special permission must be sought from the local health care administration. Standard operating procedures for harvesting and transportation of the cartilage cells are mandatory for the accreditation process.

Latest developments focus on one-step, membrane-based, scaffold-enhanced cartilage repair. Mesenchymal progenitor cells migrate toward and adhere to the porous layer of the matrix which is implanted analogue to the technique described in the following text in a one-step surgery. Whereas in

Europe, different membranes are approved for use in the talus, the FDA approval is still in progress.13,24,52,55

 

 

ANATOMY

 

A slight majority of OLTs are on the medial shoulder of the talus.18,48

 

 

Sixty-two percent of lesions are located at the medial talar shoulder; many of these are thought to be a result of OCD rather than posttraumatic.

 

Thirty-four percent of the lesions are located at the lateral talar shoulder; most are thought to be of traumatic origin. Central OLTs are rare (<5%).

 

In the anteroposterior (AP) direction, the midtalar dome (equator) is much more frequently involved (80%) than the anterior (6%) or posterior (14%) thirds of the talar dome.

 

 

Classification of osteochondral lesions is based on arthroscopic findings.28

 

 

Grade I: intact lesions

 

 

Grade II: lesions showing signs of early separation Grade III: partially detached lesions

 

Grade IV: craters with loose bodies

 

ACI is performed for symptomatic grade II-plus lesions (fullthickness cartilage defects).

 

PATHOGENESIS

 

Traumatic cartilage injuries are caused by short, intensive, greater-than-physiologic strain on the joint resulting in partial detachment of the talar dome cartilage. The depth of these lesions varies from superficial chondral abrasions to full-thickness osteochondral defects.39,51

 

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OCD is a condition most frequently found in adolescents or young adults. Although the cause remains poorly defined, theories include the following:

 

 

Chronic overload

 

 

Local disturbance of blood supply to the subchondral bone associated with the affected cartilage32

 

Degenerative cartilage defects (degenerative osteoarthritis) develop from wear and tear of the cartilage surface as part of the aging process. An individual's risk of developing primary osteoarthritis most likely depends on a genetically determined quality of the cartilage. Ankle instability and other conditions that impart eccentric or nonphysiologic loads to the cartilage may accelerate the process of degeneration. In exceptional cases, when such a degenerative process is limited to a focal portion of the talar dome, ACI may be considered for degenerative cartilage defects, provided the underlying cause leading to focal degeneration (ie, malalignment or chronic instability) is corrected.

 

NATURAL HISTORY

 

The natural history of a focal cartilage injury has not been linked to diffuse ankle arthritis.

 

 

Posttraumatic arthritis, which differs from an OLT, develops from diffuse injury to the cartilage surface that results in cartilage fibrillation and eventual eburnation. ACI is contraindicated for diffuse ankle arthritis.

 

Injury to a focal portion of the talar dome spans the spectrum from a bone bruise to a detached focal osteochondral fragment. Although an osteochondral fragment may be created at the time of injury, the focal talar dome pathology probably evolves. Many OLTs are probably asymptomatic; we know this from numerous OLTs that are found incidentally on imaging studies of the ankle obtained for reasons other than suspected intra-articular pathology. However, with persistent eccentric stresses, greater-than-physiologic loads, inadequate local blood supply, or inadequate healing time, a stable OLT may progress to an unstable one.

 

The difficulty is also in the symptomatology. Although some apparently unstable lesions may be asymptomatic, other OLTs that are clearly stable result in considerable symptoms directly related to the OLT.35

PATIENT HISTORY AND PHYSICAL FINDINGS

 

Although many patients report a specific ankle injury to account for the OLT, many do not present until months after ankle injury.14 A symptomatic OLT is in the differential diagnosis for an ankle sprain that does not heal.

 

 

However, many patients with symptomatic OLTs do not recall a specific traumatic event leading to the OLT.46 In my experience, most patients presenting with symptomatic OLTs are between 20 and 50 years of age.52 Men are more commonly affected than women (ratio 1.6:1).46

 

Patients typically describe an ache in the ankle with activity or with the first steps after a period of rest.

Occasionally, sharp ankle pain is noted with weight bearing. In our experience, mechanical symptoms of locking or catching are noted only with a completely detached osteochondral fragment. Paradoxically, OLTs may produce symptoms on the opposite side of the joint from the location of the cartilage defect.

 

Our preferred physical examination methods are listed here. Occasionally, symptoms may not be elicited on clinical examination.

 

 

Locking or catching: found when something interrupts the normal movement of the joint. However, it says nothing about the cause of this condition (eg, scar, joint body, osteochondral fragment, and synovitis).

 

Inversion test (calcaneofibular ligament [CFL]): strongly dependent on the cooperation of the patient. If positive, it is highly specific for a ruptured CFL.

 

Medial stability: strongly dependent on the cooperation of the patient. If positive, it is highly specific for a ruptured deltoid ligament.

 

Anterior drawer test (anterior talofibular ligament [ATFL]): strongly dependent on the cooperation of the patient. If positive, it is highly specific for a ruptured ATFL.

 

The medial and lateral corner of the talar dome should be palpated with the ankle maximally flexed to identify anterior or central OLTs; posteromedial palpation immediately posterior to the posterior tibial tendon (PTT) with the ankle maximally dorsiflexed may reproduce symptoms for posteromedial OLTs. Although anterolateral OLTs are relatively easy to palpate, posteromedial lesions are difficult to access adequately on physical examination.

 

We find it useful to compare the symptomatic ankle to the uninvolved contralateral ankle.

 

 

The medial and lateral corner of the talar dome should be palpated with the ankle maximally flexed to identify anterior or central OLTs; posteromedial palpation immediately posterior to the PTT with the ankle maximally dorsiflexed may reproduce symptoms for posteromedial OLTs. Although anterolateral OLTs are relatively easy to palpate, posteromedial lesions are difficult to access adequately on physical examination.

 

We typically dorsiflex and plantarflex the ankles with axial pressure while simultaneously applying eversion and inversion stresses to reproduce symptoms at the talar defect.

 

Despite appropriate provocative maneuvers, our experience has been that posterior OLTs rarely exhibit obvious clinical findings.

 

Associated injuries and other considerations in the differential diagnosis of chronic ankle pain should be evaluated, particularly because OLTs may be incidental findings. These include the following:

 

 

Ankle instability: positive anterior drawer test and inversion testing

 

Chondromatosis of the ankle: Recurrent locking of the joint and persistent effusions are typical physical findings.

 

Intra-articular scarring with load-dependent pain, mostly at the anterolateral aspect of the ankle joint

 

Inflammatory arthropathy: Although effusion and deep joint pain with weight bearing are commonly present, pain at rest and persistent joint warmth are also common features of inflammatory disease.

 

Pigmented villonodular synovitis (PVNS): Organized nodules of synovitis can mimic loose bodies with locking and effusion. Synovial swelling is not typical for osteochondral defects. MRI with contrast typically confirms the diagnosis of PVNS.

 

 

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Hindfoot malalignment with local osteoarthritis: Edge loading of the talus can cause symptomatic local cartilage lesions. Typically, those defects include the tibial cartilage as well as the talus, which can be visualized with MRI.

 

IMAGING AND OTHER DIAGNOSTIC STUDIES

 

Plain radiographs of the ankle joint, including AP, mortise, and lateral views, are obtained to rule out late-stage degenerative arthritis.

 

MRI with contrast is highly sensitive and specific in diagnosing osteochondral lesions as well as associated injuries.30,41

 

Osteochondral lesions were first classified by Berndt and Harty8 based on plain radiographs:

 

 

Stage I: compression lesion; no visible fragment

 

Stage II: beginning avulsion of a chip

 

 

Stage III: chip, completely detached but in place Stage IV: displaced chip

 

Plain films typically offer limited information on the size and extent of the lesion and may even miss the OLT. MRI, computed tomography (CT), and arthroscopic evaluation provide greater detail of OLTs than plain radiographs.

 

DiPaolo classification of osteochondral lesions based on MRI15

 

 

Stage I: thickening of articular cartilage and low signal changes

 

Stage II: articular cartilage breached, low signal rim behind fragment indicating fibrous attachment

 

Stage III: articular cartilage breached, high signal changes behind fragment indicating synovial fluid between fragment and underlying subchondral bone (FIG 1)

 

Stage IV: loose body

 

 

Based on the greater detail of pathologic anatomy, Hepple et al30 revised the classification and included a stage V (subchondral cyst formation).

 

 

Stage I: articular cartilage damage only

 

 

Stage IIa: cartilage injury with underlying fracture and surrounding bony edema Stage IIb: stage IIa without surrounding bony edema

 

 

 

Stage III: detached but undisplaced fragment Stage IV: detached and displaced fragment Stage V: subchondral cyst formation

 

The Ferkel and Sgaglione CT classification is used for preoperative planning purposes and to learn the size of the subchondral defect.20

 

Stage I: cystic lesion of the talar dome with an intact roof

 

Stage IIa: cystic lesion with communication to the talar dome surface

 

 

Stage IIb: open articular surface lesion with an overlying, nondisplaced fragment Stage III: nondisplaced lesion with lucency

Stage IV: displaced osteochondral fragment

DIFFERENTIAL DIAGNOSIS

Syndesmosis injury Intra-articular scarring

Subluxation or tear of peroneal tendons Fracture or disruption of the os trigonum Malleolar avulsion fracture

Interosseous ligament injury

 

 

 

 

FIG 1 • A. Arthroscopic view of a full-thickness osteochondral defect at the talar dome. B. Corresponding MRI.

 

 

 

 

Anterior process fracture of the calcaneus Lateral shoulder fracture of the calcaneus Chondromatosis

 

 

Inflammatory joint disease PVNS

 

Degenerative arthritis

 

NONOPERATIVE MANAGEMENT

 

In young patients with open physes, OCD can be managed conservatively with a high rate of complete remission (FIG 2).7,53

 

Acute osteochondral lesions may be treated conservatively. Acute lesions (stages I and II) require 3 weeks of immobilization. Stages III and IV lesions should be treated with a walker and partial weight bearing of 20 kg for

6 weeks.46 However, unstable osteochondral lesions, particularly those with detached fragments, should be managed operatively.

 

Incidentally discovered OLTs and OCD cases in adults are generally treated expectantly with regular follow-up.17,53

 

The literature suggests that chronic OLTs, even larger lesions, may be treated nonoperatively as well.49 Nonoperative treatment comprises nonsteroidal anti-inflammatory agents, ankle bracing, physiotherapy, corticosteroid injection, and viscosupplementation. Currently, no conservative treatment of OLTs allows resurfacing or healing of the cartilage defect.

 

 

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FIG 2 • A. OCD in a child with open physis. B. Six months later, the lesion is healed with conservative treatment.

SURGICAL MANAGEMENT

 

Microfracture

 

 

Arthroscopic débridement and microfracture generally represent the initial surgical management for the vast majority of OLTs, with satisfactory results in 65% to 90% of patients.6,31,45

 

After arthroscopic débridement of the OLT, the defect's subchondral bone is penetrated with multiple noncontiguous passes of a specialized awl to permit the débrided defect to be populated with undifferentiated stem cells from the deeper tissues.

 

Over the next few months, these cells reorganize into (type II) fibrocartilage.

 

The biomechanical properties of fibrocartilage are different from those of hyaline cartilage; the fibrocartilage does not function in concert with the surrounding physiologic hyaline cartilage. The literature suggests that microfracture is successful in a majority of relatively small OLTs (up to 2 cm2).6,25

 

Autologous osteochondral transfer (osteochondral autograft transplantations [OATS] or mosaicplasty) and ACI are typically secondary surgical procedures when arthroscopic débridement and microfracture and drilling fail.

 

Due to inferior outcome of microfracture in OLTs larger than 2 cm2, ACI can be considered as primary surgery in large defects.12

 

Autologous osteochondral cylinder transplantation (OATS or mosaicplasty)29,47

 

 

In the OATS or mosaicplasty technique, osteochondral cylinders or plugs are harvested either from a low load-bearing area of the knee or from the medial or lateral facet of the talus. These plugs are transplanted into the defect area, which has been prepared to the appropriate size.

 

This procedure fills large portions of the defect surface with high-quality hyaline cartilage.25

 

 

The results of this technique are satisfactory, but donor site morbidity occurs in up to 50% of cases.43 To limit these harvesting symptoms, osteochondral cylinder transplantation (OCT) can be successfully applied for cartilage defects of up to only about 3 cm2. Matching defects on the talar shoulder are difficult

with this technique, despite technique modifications described by Hangody.29 Moreover, the characteristics

 

of talar cartilage differ from those of cartilage from the knee.11 Allograft osteochondral cylinder transplantation27

 

If available, osteochondral cylinders can be taken from a fresh or fresh frozen cadaver talus.

 

 

Immunologic reactions have posed little problem to date.37

 

Preoperative Planning

 

All imaging studies are reviewed, with MRI providing detail of the cartilage defect and CT providing detail of subchondral bone involvement.2,16,47

 

Pure cartilage defects or shallow osteochondral defects can be managed with the conventional ACI procedure; deeper osteochondral defects require a “sandwich technique.”

 

The sandwich technique involves two layers of periosteum. The defect is prepared and bone grafted to recreate the subchondral bone architecture. On this, the first layer of periosteum is placed cambium layer up.

Then, the defect can be treated in the conventional manner: The second layer of periosteum is placed cambium side down. The cultured cartilage cells are injected between these two layers. Alternatively, the cartilage defect may be bone grafted in a first stage, with a conventional ACI procedure being performed in a second stage. This is feasible in the knee but more challenging in the ankle, which may require ligament release or osteotomy for adequate exposure, procedures that should not be performed more than once if not necessary.

 

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 less demanding. Matrixbased chondrocytes can be glued into the

defect which often allows to address the lesion without medial malleolar osteotomy.56

 

Ankle malalignment and instability should be identified and corrected in conjunction with ACI if possible.

 

Positioning

 

Harvesting chondrocytes: standard arthroscopy of the ankle or the knee

 

 

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Giannini et al23 have demonstrated that the detached OLT fragment at the time of index arthroscopy may be an acceptable source of chondrocytes in ACI. Another possible source is the anterior aspect of the talus.5

 

Transplantation of chondrocytes: Depending on the location of the defect, the patient is positioned supine with a slightly internally or externally rotated leg. If iliac crest graft is to be obtained, the pelvis needs to be prepared and draped as well and the ipsilateral pelvis supported with a bump. Alternatively, bone graft may be harvested from the calcaneus, distal tibia, or proximal tibia, all locations within the surgical field typically

prepared for ACI.19,21,42 A vacuum mattress can be helpful to adjust the patient's position during the procedure (FIG 3).

 

 

 

FIG 3 • Standard positioning in a supine position.

 

TECHNIQUES

  • Approach

     

    Harvesting chondrocytes: Medial and lateral anterior portals and a posterolateral portal give an adequate overview of the joint and allow the harvesting of chondrocytes.

     

    Transplantation: Depending on the location of the OLT, a medial approach between the medial malleolus and the PTT, 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 OLT.22,25 Except for OLTs at the anterior or posterior margins of the talar dome, ACI cannot be performed properly without medial malleolar osteotomy for extensive medial OLTs and ATFL-Cflrelease, lateral malleolar osteotomy, or both for extensive lateral OLTs.

     

    A major advantage compared to mosaicplasty or OATS is that a perpendicular access is not required.

    Muir et al36 demonstrated that the majority of the talar dome can be accessed without osteotomy but acknowledged that osteotomies are required to adequately expose extensive OLTs.

  • Medial Osteochondral Lesions of the Talus

     

    Occasionally, the ACI procedure can be performed for medial OLTs with an anteromedial or

    posteromedial arthrotomy.36 In our experience, these are exceptional cases, often requiring extreme intraoperative ankle plantarflexion and dorsiflexion for anteromedial and posteromedial lesions, respectively. An intact deltoid ligament permits little if any translation of the talus relative to the tibia. Access to an anterior defect can be enhanced with a groove created in the anteromedial tibia but leaves a permanent defect in the anterior weight-bearing surface of the plafond. We appreciate that extreme dorsiflexion allows visualization of some posteromedial OLTs; however, we caution against extreme dorsiflexion that tensions the posteromedial neurovascular bundle in combination with the simultaneous required retraction of the neurovascular bundle to allow proper access to the lesion. One author

    suggested that a medial malleolar window can be created, obviating the need for osteotomy,40 but we have no experience with this approach.

    Oblique Medial Malleolar Osteotomy

     

    A longitudinal incision is centered over the medial malleolus, similar to that performed for open reduction and internal fixation of medial malleolar fractures.

     

    An anterior arthrotomy serves to identify the junction between the medial malleolar and tibial plafond articular surfaces and may allow visualization of the anterior aspect of the OLT.

     

    Posteriorly, the flexor retinaculum is opened, and the PTT is identified directly on the posterior tibia. The PTT rests in a groove in the posterior aspect of the medial tibia in its own sheath; the flexor digitorum longus tendon lies directly posterior to the PTT and should not be mistaken for the PTT.

     

    With the PTT properly retracted, the posteromedial neurovascular bundle will also be protected.

     

    The medial malleolar osteotomy requires minimal periosteal stripping; in fact, we advise leaving as much of the periosteum as possible on the medial malleolar fragment to maintain blood supply for healing.

     

    To optimize reduction of the medial malleolar osteotomy after the cartilage repair procedure, we recommend predrilling the medial malleolus. Two parallel drill holes are placed extra-articularly perpendicular across the desired osteotomy, in the same orientation as screws placed for conventional open reduction and internal fixation for medial malleolar fractures. The proper course for these drill holes

    is confirmed fluoroscopically, both in the AP and lateral planes.

     

    Under fluoroscopic guidance, a Kirschner wire pin is introduced obliquely to dictate the desired plane of the osteotomy. Typically, we introduce this guide pin slightly more proximal and medial than the intended course of the osteotomy to allow access for the saw blade, chisel, or both without having to remove the pin that guides our osteotomy.

     

    The osteotomy can be planned more conservatively as in mosaicplasty because a perpendicular access to the OLT is not needed. As a rule, we plan to have the osteotomy enter the tibial plafond at the medial extent of the OLT.

     

    With the plan for the osteotomy determined, the periosteum is divided transversely, again leaving the majority of the periosteum intact. With cold saline or sterile water irrigation to reduce the risk of osseous heat necrosis, a microsagittal saw is used to perform the oblique osteotomy to the level of the tibial plafond subchondral bone.

     

    The joint is penetrated with an osteotome or a chisel. Intermittent fluoroscopic guidance is recommended to confirm proper saw blade or chisel orientation and that the talar dome is not injured during the final stages of the osteotomy.

     

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    The medial malleolus is then reflected, suspended by the deltoid ligament.

     

    Even with careful technique, the osteotomy rarely separates in a uniform plane. Particularly posteriorly, a slight irregularity is observed. This is of little concern, however, as these irregularities will provide greater stability when the osteotomy is reduced.

     

    To fully displace the medial malleolar fragment, the PTT sheath must be released from the medial malleolus.

     

    At the conclusion of the cartilage resurfacing procedure, the medial malleolus is reduced and secured with two malleolar screws placed in the predrilled tracks with compression.

     

    To limit a vertical shear effect, an antiglide screw or plate may be placed at the proximal aspect of the osteotomy. Alternatively, a third screw can be carefully placed from medial to lateral eccentrically across the osteotomy in addition to the two predrilled compression screws.

     

    Anatomic reduction is confirmed clinically by visualizing the anterior and posterior aspects of the osteotomy and fluoroscopically in the AP and oblique planes. Fluoroscopy in all three routine views of the ankle confirms proper extra-articular position of the screws.

     

    Due to the thickness of the saw blade, a slight, incomplete gap may be visualized at the osteotomy site in select cases; despite this immediate postoperative finding, our anecdotal experience has been that the oblique medial malleolar osteotomy heals in its anatomic position with few complications.

  • Lateral Osteochondral Lesions of the Talus

     

    ATfland Cflrelease: Some lateral OLTs are associated with lateral ankle instability.33 This combination of pathology is well suited to surgical management because a modified Brostrom procedure is required to stabilize the ankle. If a lateral OLT is identified without lateral ankle instability, lateral ligament release to allow access to the OLT is readily repaired with a modified Brostrom technique, particularly because the

    lateral ankle ligaments are not attenuated.47

     

    The fibula is exposed through a longitudinal incision. If ligament release is inadequate, the extensile longitudinal incision facilitates the addition of a lateral malleolar osteotomy. Moreover, if associated pathology involves the peroneal tendons, the extensile longitudinal approach is necessary.

     

    With the sural nerve protected posteriorly and inferiorly and the lateral branch of the superficial peroneal

    nerve protected anteriorly, the inferior flexor retinaculum is identified and isolated.

     

    Deep to the retinaculum and at the distal and posterior margin of the fibula, the peroneal tendons are identified and protected throughout the procedure.

     

    The ATfland Cfllie within the lateral ankle capsular complex. Leaving a 1-mm cuff of capsule on the distal fibula, the capsule and the ATfland Cflare released. The ankle is plantarflexed and inverted; the talus is subluxated anteriorly out of the ankle mortise to expose the OLT.

     

    After the cartilage resurfacing, the talus is reduced in the ankle mortise and a modified Brostrom procedure is performed. This can be done with suture anchors in the distal fibula, placed to secure the ATfland Cflcomponents of the lateral ankle capsule in particular or with transosseous sutures.

     

    During tensioning of the ligament repair, the talus is maintained posteriorly (avoiding anterior translation), with the ankle in a neutral sagittal plane position and the hindfoot in slight eversion. As described by

    Gould,26 the inferior extensor retinaculum is advanced to the distal fibula to lend greater stability to the repair.

    Lateral Malleolar Osteotomy

     

    Several different patterns for lateral malleolar osteotomies exist; surprisingly, few have been described in detail. We typically employ an oblique fibular osteotomy, similar to the pattern created by a simple Weber B ankle fracture. The approach is as described for the ligament release earlier. As for a medial malleolar osteotomy, periosteal stripping is kept to a minimum, predrilling is preferred, and cold saline or sterile water irrigation is applied to the osteotomy site to limit osseous heat necrosis.

     

    Before performing the osteotomy, we position a small fragment plate in the desired position and predrill the holes. With the soft tissues protected, in particular the superficial peroneal nerve and the peroneal tendons, the oblique osteotomy is created from anterior to posterior using a microsagittal saw. The syndesmotic ligaments are not disrupted. Release of the ATfland Cflin combination with the fibular osteotomy can be considered to improve exposure of larger posterolateral OLTs with medial extension.

     

    At the conclusion of the cartilage repair procedure, the fibula is reduced and secured with the predrilled lateral fibular plate. Reduction is confirmed with intraoperative fluoroscopy. Before placing the plate, a lag screw may be placed across the osteotomy, but we do not routinely do so.

     

    As for the medial malleolar osteotomy, the thickness of the saw blade may lead to a slight, incomplete gap at the fibular osteotomy site in select cases. Again, despite this immediate postoperative finding, our anecdotal experience has been that the oblique medial malleolar osteotomy heals in its anatomic position with few complications.

  • Central Defects

     

    As observed in the cadaver model of Muir et al,36 perpendicular access to the central talar dome is not

    possible via medial and lateral osteotomies. Tochigi et al50 described a Chaput lateral tibial osteotomy, similar to a Tillaux fracture, to allow greater medial exposure to extensive lateral OLTs; however, Muir et

    al36 noted that this osteotomy still fails to allow access to the central talar dome.

     

    The trapdoor osteotomy described by Sammarco and Makwana,44 in which an anterior osteochondral wedge is removed from the distal tibia, may permit access to select anterocentral OLTs. Although attractive, the osteotomy must be carefully planned to accommodate the instrumentation at the ideal location for sufficient access, as coronal plane translation of the talus is not possible. Moreover, access to relatively rare posterocentral lesions is still not possible despite this novel approach.

     

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  • Harvesting of Chondrocytes

     

    Complete diagnostic arthroscopy and identify all pathology.

     

    Using a curette, harvest two or three full-thickness articular grafts that include the superficial layer of subchondral bone (TECH FIG 1). 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 about 2 to 6 weeks, depending on the company and the preferred culturing process.

     

    Ensure that the cells are sent to the company immediately, the “cool chain” is sustained, and the required documents are included in the box.

     

     

     

    TECH FIG 1 • A. Harvesting cartilage with a curette from the ventral aspect of the talus. B. Grasping the small piece of cartilage for culturing.

  • Autologous Chondrocyte Transplantation

 

To avoid compromising chondrocyte viability, use a tourniquet to maintain a bloodless field.

 

We typically use a thigh tourniquet; although a calf tourniquet is possible, compression of the lower leg musculature may restrict exposure and manipulation of the ankle, thereby compromising exposure.

 

Expose the transplantation site. Despite adequate exposure with appropriate osteotomies or ligament releases, performing the second ACI stage for the ankle, in particular suturing the periosteal flap, may prove tedious. 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 optional. For the knee, both techniques have proven to have similar clinical outcomes.3 At the talus, there is still a lack of scientific evidence, but our extended anecdotal experience has shown similar results in both techniques.

 

Débride all unstable cartilage with a curette to create a healthy, stable cartilage rim. The subchondral bone in the defect should be intact.

 

If a shallow bony defect exists, remove the sclerotic bone. Despite tourniquet use, some bleeding may be encountered; it should be controlled with an epinephrine sponge or a minimal amount of fibrin glue.

 

In the event of a deeper defect, use the sandwich technique described earlier to recreate subchondral support for the transplanted chondrocytes. Any bony cyst has to be filled with autologous bone graft,

preferably from the iliac crest or the proximal tibia.21

 

Impact the graft to provide a smooth surface for the transplantation site.

 

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).

Technique with Periosteal Flap

 

By exposing the distal tibia just proximal to the ankle, identify an appropriate area for periosteal flap harvest; exposure is to the level of the periosteum without violating it.

 

Place the template on the periosteum and mark an outline 1 to 2 mm greater than the template on the periosteum. The periosteal harvest should be slightly larger than the template, as periosteum tends to recoil or shrink slightly after harvest.

 

Perform sharp dissection to bone on the marked periosteum circumferentially. With a sharp periosteal elevator, elevate the periosteum, with its cambium layer, directly off the underlying tibia without creating defects in the periosteal graft. We routinely place a mark on the superficial layer of periosteum before detaching the periosteal flap from the tibia to be certain we can identify the cambium layer at the time of transfer to the talus.

 

Carefully separate overlying fibrous tissue or fat from the periosteal graft.

 

After ensuring that the OLT is bloodless, transfer the periosteal flap to the OLT, with the cambium layer facing the defect.

 

Suture it using interrupted 6-0 Vicryl to the surrounding articular cartilage, with sutures spaced at intervals of about 3 mm. To optimize tensioning, the corners can be anchored first. Place the knots on the articular cartilage rather than the periosteal flap. The final suture is omitted at this point, with the residual defect being at the area of easiest access for chondrocyte transplantation.

 

Apply fibrin glue around the periphery of the periosteal flap's junction with the healthy articular cartilage, particularly between the sutures.

 

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Using a flexible angiocatheter, inject sterile saline into the residual opening to confirm a watertight seal; any leakage of saline should emanate only from the residual opening. Add sutures, fibrin glue, or both as needed.

 

The chondrocytes are delivered in a vial that is sterile internally but not externally. The vial can be placed on a separate back table while the surgeon maintains sterile technique while resuspending and extracting the chondrocytes from the vial into a sterile angiocatheter.

 

Through the residual opening under the periosteal flap, introduce the angiocatheter into the defect. The chondrocytes are evenly distributed with the surgeon gently injecting the suspension.

 

 

Remove the angiocatheter and seal the residual aperture with a final suture and more fibrin glue. After the fibrin glue has cured, ankle range of motion confirms that the periosteal flap is stable.

 

Stabilize the ankle joint with repair of the ligaments or osteotomy, depending on the particular approach.

 

ACI has not been perfected for shoulder lesions of the talus. However, as for the femoral trochlea, a carefully executed suture pattern can allow the periosteum to be draped over a shoulder lesion to recreate, at least to some degree, the physiologic contour of the talus. With the periosteum first tensioned at the shoulder and secondarily on the dorsal and mediolateral aspects of the talus, ACI can be effective for select talar shoulder OLTs.

 

 

 

TECH FIG 2 • A. Traumatic osteochondral lesion at the medial talar dome after removing the unstable cartilage and the subchondral cyst. The sclerotic wall of the cyst shows several drillholes. B. Defect filled with autologous bone graft. C. Container with the matrix induced condrocytes, ready for transplantation. D. Matrix-induced chondrocytes transplanted into the defect and fixed with fibrin glue.

Technique with Matrix-Induced Autologous Chondrocytes Implantation

 

The technique with matrix-induced chondrocytes requires no further preparation after the size of the defect is measured. The matrix is stable and can be fixed directly to the OLT.

 

Take care when removing the transplant from the transport container. In particular, avoid squeezing the transplant (TECH FIG 2A,B).

 

Cut the transplant according to the size of the defect. Some companies provide special punches for this step. The size of the transplant should meet exactly the size of the defect. Preparing the transplant 2 mm larger, as recommended for the periosteal flap, can lead to overlaying edges and a lack of stability.

 

Place the transplant into the defect. A first fixation happens due to adhesion forces. The edge can then be stabilized with 6-0 sutures and fibrin glue (TECH FIG 2C,D).

 

Check the transplant for stability by carefully moving the ankle joint into dorsiflexion and plantarflexion. We recommend that postoperative mobilization be limited so that the transplant is always covered at least partially by the tibial plafond to prevent shear forces. The optimal postoperative range of motion can be checked in this step.

 

Insert one intra-articular tube before closing the wound. Stabilize the ankle joint with repair of the ligaments or osteotomy, depending on the particular approach.

 

 

 

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PEARLS AND PITFALLS

 

Indications and planning

  • Address associated pathology.

  • Generalized osteoarthritis is a contraindication.

  • Absence of clinical instability

  • Intact cartilage at the corresponding tibial side

  • The extent of cartilaginous detachment is often underestimated on MRI, whereas the bony reaction tends to be overestimated.

  • OLTs with subchondral cysts respond poorly to drilling or microfracturing. In these cases, ACI or MACI can be considered as a primary procedure.

  • ACI and MACI are not indicated in the face of diffuse ankle arthritis; these procedures are intended for focal defects only.

     

    Harvesting ▪ Take extreme care 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 ▪ This service is provided by several companies. They provide the medium for harvesting the chondrocytes and, in some cases, special tools for harvesting and transplantation.

       

      Transplantation ▪ Be careful to prepare the transplant large enough.

    • Adequate exposure is mandatory for ACI or MACI. This often requires a malleolar osteotomy.

    • Intraoperative radiographs should be taken before performing an osteotomy and after the osteosynthesis. The osteotomy should be adequate to gain sufficient access to the OLT.

    • Do not squeeze the transplant (MACI).

    • Be sure that the periosteal flap is watertight before injecting the chondrocytes (ACI).

       

      Rehabilitation ▪ Follow the rehabilitation plan; it takes time for the graft to gain 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, the ankle joint is stabilized with a dorsal splint.

 

Immediately postoperatively, the patient should have 48 hours of bed rest. The ankle should not be moved and is fixed with a brace.

 

Forty-eight hours postoperatively, drainage tubes are removed and the joint is mobilized with continuous

passive motion. Limitations can occur in large defects or extended ligament repair.

 

During the first 6 weeks postoperatively, the patients are allowed partial weight bearing (10 kg) and mobilization without weight bearing including accompanying physiotherapy (similar to the postoperative scheme in complex ankle fractures with open reduction and internal fixation).

 

After 6 weeks, a gradual increase in joint loading is allowed (20 to 30 kg every 2 weeks) up to full body weight.

 

After 12 weeks, full weight bearing in activities of daily life is allowed, including cycling with moderate resistance and swimming.

 

After 6 months, increased athletic 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, we have seen most patients able to return to recreational sports.

 

It is unclear whether patients can return to contact sports and sports that place high physical demands on the ankle joint. So far, there are no data available.

 

OUTCOMES

 

There are only limited data on this new treatment concept and no long-term studies.

 

Brittberg et al9 reported the results of their first 14 consecutive patients managed with ACI for the ankle. At an average follow-up of 45 months, 12 were considered improved, with 11 having good to excellent outcomes.

 

Baums et al5 found an improvement in the American Orthopaedic Foot and Ankle Society (AOFAS) ankle score from 43.5 to 88.4 in a prospective study of 12 patients.

 

Giannini et al22 reported an average AOFAS hindfoot-ankle score improvement from 26 points to 91 points at a mean follow-up of 26 months. Histologic analysis of biopsies obtained at 12 months suggested hyaline cartilage in all eight specimens.

 

In another series, Giannini et al23 demonstrated no statistically significant difference in 16 patients undergoing ACI with chondrocytes cultured from the detached OLT fragment compared to 7 patients undergoing ACI with chondrocytes harvested from the patient's ipsilateral knee. In both groups, the average AOFAS hindfoot-ankle score improved from 54 points to about 89 or 90 points. Histologic appearance, expression of specific cartilage markers, cell viability, cell proliferation in culture, and redifferentiation were favorable, and the morphologic and molecular characters of the cultured

 

chondrocytes from the detached fragment were similar to those of physiologic hyaline cartilage.23 By culturing the chondrocytes from the detached chondral fragment, donor site morbidity can be avoided.23 However, by taking small chips of cartilage from 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.43

 

MRI imaging after ACI can be challenging, edema can be found more than 12 months after implantation, especially in extended bone grafts. Incomplete integration of bone graft, nonintact subchondral lamina, high signal intensity, and extended edema were found to correlate with worse clinical functional

outcomes.10

 

Improvement of results can continue for several years.4

 

 

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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 that cultures the cartilage cells. One possibility is to do another arthroscopy to get cartilage cells; however, other treatment options like OATS or allograft can be considered.

 

Delayed union in the malleolar osteotomy: 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 progression toward healing is not noted to limit the risk of displacement of the osteotomy.

 

Failure of the transplanted tissue includes detachment of the transplant, delamination, or ossification.

Especially in the periosteal flap technique, ossification is a common cause of failure.38 Ossification in the MACI technique has not yet been reported.

 

Resorption of the subchondral bone graft in stage V lesions treated using the sandwich technique can lead to a graft failure.

 

Hypertrophy: Fibrous tissue may form at the graft-host articular junction or within the ankle, causing impingement, and can be effectively débrided to relieve symptoms. ACI in particular is subject to fibrillation or hypertrophy, and arthroscopic débridement, in select cases, is essential to remove

mechanical symptoms and avoid delamination of the graft.9

 

The source of pain from an OLT remains ill defined, and the success of cartilage resurfacing procedures is certainly not 100%. Therefore, even without any obvious complication, pain may persist.

 

If the clinical outcome is not satisfactory and follow-up imaging studies suggest graft compromise, ankle arthroscopy is warranted. Although failure of graft incorporation or delamination of the resurfaced articular segment is perhaps irreversible, not all persistent symptoms are necessarily due to such phenomena. 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 of persistent knee symptoms. The reported prevalence of persistent knee symptoms ranges from less than 10%22,29,47 to

50%.43 It is important to educate patients about this risk preoperatively. Because Giannini et al23 has demonstrated no statistically significant difference between chondrocytes cultured from the detached OLT fragment versus chondrocytes harvested from the patient's ipsilateral knee, we always harvest

chondrocytes from the ankle joint to minimize the risk of donor site problems.5 Based on our extended anecdotal experience doing so, we have seen no disadvantage with this concept.

 

General surgical complications such as deep venous thrombosis, wound healing problems, or infection are also possible.

 

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