Instructional Course 205
Autologous Chondrocyte Implantation of the Talus Bert R. Mandelbaum, M.D., Michael B. Gerhardt, M.D., and Lars Peterson, M.D.
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utologous chondrocyte implantation (ACI) was first attempted in 1987 for treatment of articular cartilage lesions of the knee.1 Long-term studies with up to 9-year follow-up have recently been reported with promising results.2 Consequently, the use of ACI has expanded to other parts of the body. Although the data and follow-up is limited, the implementation of ACI in other joints including the shoulder, elbow, and ankle has been reported.3-5 The general goals of ACI, regardless of the joint involved, is to decrease pain and swelling, maximize function, prevent joint degeneration, and maintain or improve the patient’s position on the chondropenia curve. The authors discuss the use of ACI in the ankle and focus specifically on the technical aspects of ACI in chondral and osteochondral injuries of the talus.
CHONDRAL AND OSTEOCHONDRAL INJURIES OF THE ANKLE Chondral and osteochondral injuries of the ankle occur with a reported overall incidence rate of 0.09%. The incidence is expected to rise as diagnostic accuracy improves with advancements in imaging techniques and with an increasing number of ankle arthroscopies being performed each year.6 In ankle injuries in general, the talus is the most commonly injured articular structure. It is estimated that osteochondral injuries of the talus occur in approximately 6.5% of all ankle sprains, usually associated with a sporting injury involving an inversion or eversion stress to the ankle.7
Address corresponding to Bert R. Mandelbaum, M.D., 1301 20th St, Suite 150, Santa Monica, CA 90404, U.S.A. E-mail:
[email protected] © 2003 by the Arthroscopy Association of North America 0749-8063/03/1910-0120$30.00/0 doi:10.1016/j.arthro.2003.09.039
The percentage increases proportionately with the severity of the trauma sustained. Osteochondral defects of the talus are commonly referred to as osteochondritis dissecans (OCD). Debate exists as to the appropriateness of the term OCD, as it has been used to refer to a variety of chondral and osteochondral lesions, both acute and chronic. Regardless of terminology, the most important distinction to make is if the lesion is acute or chronic; as the literature clearly shows, acute lesions respond more favorably to both conservative and surgical treatments.8 OCD lesions of the talus account for approximately 4% of all osteochondral lesions in joints.9 The term was coined by Kappis in 1922 when he described a lesion characterized by detachment of a portion of the articular cartilage and the underlying subchondral bone which forms a loose body within the ankle joint.10 In 1959, Berndt and Harty were the first to propose a relationship between trauma and the OCD lesion of the talus.11 Although controversial, this relationship reflects the current concensus as to the etiology of most of these lesions. It appears that the traumatic insult to the cartilage results in localized vascular compromise to a discreet part of the talus. Because the blood supply to the talus is tenuous, even minor trauma to the chondral and subchondral areas can be devastating, ultimately resulting in an OCD lesion (Fig 1). Clearly the etiology is multifactorial as shown by the fact that approximately 7% to 15% of patients with talar OCD lesions do not report any history of trauma.8 Regardless of cause, the treatment principles remain similar for osteochondral defects in general. PREOPERATIVE PLANNING AND PHYSICAL EXAMINATION Patients with a chondral or osteochondral injury of the talus typically complain of persistent ankle pain
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B. R. MANDELBAUM ET AL. study and is widely used to evaluate a suspected lesion if the plain radiographs are unremarkable. We advocate MRI as the study of choice for all patients with suspected OCD lesions regardless of the appearance on plain film radiographs, as we can pick up occult chondral and osteochondral lesions, while at the same time accurately stage the lesion. The staging system according to the modified Berndt and Harty system is helpful in classification and in planning a treatment strategy.12 Conservative treatment should be exhaustively attempted for a minimum of 6 weeks in all patients with low-grade, stable lesions. Nonoperative treatment should be pursued for a longer period in younger patients. Conservative treatment modalities include immobilization, weight-bearing limitations, and physical therapy. Therapeutic exercise includes strengthening, proprioceptive training, and ankle range of motion drills. Overall, conservative treatment for symptomatic OCD lesions has a reported success rate of 25% to 37.5%.13,14 For patients who fail conservative treatment and in patients with high-grade or unstable lesions, diagnostic arthroscopy should be performed.12,13,16
DIAGNOSTIC ARTHROSCOPY AND LESION ASSESSMENT
FIGURE 1. (A) Radiograph of a displaced osteochondral defect of the talus. (B) MRI of an osteochondral defect of the talus.
with weight bearing, frequent stiffness, and activity related swelling. Occasionally, catching, locking, and giving way are reported. Physical examination findings are often vague but can include joint effusion, pain with provocative testing, limited dorsiflexion and/or plantarflexion, and possibly concomitant laxity if chronic ankle instability is present. The radiographic workup should begin with a standard ankle series including anteroposterior, lateral, and mortise views. Stress views should be obtained if instability is suspected. Loomer et al. report that 50% to 66% of OCD lesions of the talus can be visualized on plain radiographs alone.12 Historically, computed tomographic scan was the recommended study for characterization and staging of the lesion and is commonly used in many centers today. Magnetic resonance imaging (MRI) is another excellent imaging
Before any type of surgical intervention, it is critical to anticipate the potential need for ACI in the future, should the lesion not respond to initial treatment. An informed consent should be obtained for articular cartilage biopsy from the ipsilateral knee as indicated. Diagnostic ankle arthroscopy is carried out via standard medial and lateral arthroscopic portals, with accessory portals placed as needed.15 The ankle should be systematically inspected and all pathology documented. Careful assessment and probing of the articular surfaces is performed, including the medial and lateral malleoli, the talar trochlea and tibia. Depending on the arthroscopic findings, various treatment modalities can be employed as first-line attempts to heal the osteochondral defects present. These techniques include debridement, curettage, bone grafting, microfracture, fragment excision, subchondral drilling, and metallic or bioabsorbable internal fixation. Successful results of these interventions overall are reported to be between 36% and 81%.16-19 At the conclusion of the initial ankle arthroscopic procedure, knee arthroscopy should be performed for cartilage biopsy.
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CARTILAGE BIOPSY Cartilage biopsy should be obtained from the ipsilateral knee via standard antermedial and anterolateral arthroscopic portals. Articular cartilage should not be harvested from the ankle because even the small amount needed for cellular cultivation is potentially detrimental to the mechanics of the ankle joint.20 The recommended sites for biopsy are at the articular margins of 1 of 3 sites on the femoral articular cartilage of the ipsilateral knee21: the superior lateral, superior medial, or lateral edge of the intercondylar notch (our preferred biopsy site). Three full-thickness cartilage biopsies measuring 3 to 4 mm wide and 10 mm in length should be obtained using a sharp curette. Each biopsy specimen should roughly correspond to the size of a kernel of corn. The cartilage biopsy should be sent to the Genzyme lab for processing as per the usual protocol for enzymatic degradation and cell culturing. The process is described in detail in the original works by Peterson et al.22 and Brittberg et al.1
AUTOLOGOUS CHONDROCYTE IMPLANTATION TECHNIQUE Cell implantation can be performed as soon as 14 days after the initial arthroscopic biopsy. A preoperative plan can be made based on the intial ankle arthroscopy. The important variables to consider include the size and dimensions of the lesion, the location of the lesion, and whether an osteotomy will be required. The need for bone grafting via the “sandwich technique” is predicated on the depth of the talar lesion. The need for osteotomy depends on both the size of the lesion and the exact location. Additionally, the decision to perform a concomitant ankle stabilization procedure should be predetermined so that the appropriate surgical approach can be made. Osteotomy and Lateral Ligamentous Stabilization The decision to perform an osteotomy depends on the zone of the talus involved. In general, a medial osteotomy is used for lesions along the medial and mid aspects of the talus. A lateral osteotomy is used for lesions along the lateral aspect of the talus. If a lateral ligament reconstruction is indicated, then an anterolateral lesion can be addressed simultaneously. The incision used for the lateral ligamentous stabilization procedure can also be used to access the anterolateral aspect of the talus with the foot in a max-
FIGURE 2. Sharp border of OCD after meticulous debridement of the base and edges of the lesion.
imally plantarflexed position, thus obviating the need for an osteotomy. Under fluoroscopy, the osteotomy should be started with an oscillating saw, and then is completed with an osteotome. Fixation of the medial malleolar osteotomy is accomplished using 2 parallel partially threaded cancellous screws, which should have been predrilled prior to osteotomy. The lateral malleolar osteotomy should be fixed using a small fragment plate and screws. Preparation of the Lesion Once access to the lesion is gained, meticulous curettage of the cartilage and osseous defect is carried out. The border of the defect should consist of clean, vertical walls of articular cartilage. This can be accomplished using a No. 15 blade to circumscribe the border back to a rim of healthy articular caritilage (Fig 2). The bed of the OCD should be aggressively debrided with a ring curette to ensure the removal of all fibrous tissue, but the subchondral bone should not be violated so as to avoid bleeding. If the depth of the lesion extends beyond the subchondral bone, then the sandwich technique should be considered, which is discussed below. Next, a template of the defect is constructed using aluminum foil. To help prevent excessive bleeding, cotton pledgets soaked with thrombin are applied to the bed of the lesion and left in place while harvesting the periosteal patch. Harvesting the Periosteal Graft Depending on the arthrotomy being used, the incision can be extended proximally as needed to harvest the periosteal patch from the distal tibia (Fig 3). The precontoured foil template is placed onto the perios-
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FIGURE 3.
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Harvesting of the periosteal graft from the distal tibia.
teum and a full thickness cut is made using a No. 15 blade. It is important to extend beyond the actual margin of the template by at least 2 to 3 mm to ensure adequate coverage of the cartilaginous defect. A periosteal elevator is then used to carefully remove the periosteal graft. It is helpful to mark the outer periosteal layer with a sterile pen so that this can be differentiated from the cambium layer. It is kept moist with saline solution until ready for attachment to the defect. Cell Implantation With the cambium layer facing the defect, the periosteal graft is placed over the defect and the adequacy of the graft size is confirmed. The graft should be carefully trimmed so that an exact fit is made without any overhanging excess periosteum. No. 6-0 vicryl suture is used to attach the periosteal patch to the articular cartilage border at the four corners of the defect. Tension on the graft is avoided. The rest of the sutures are now placed such that spacing averages 2 to 3 mm apart (Fig 4). A small defect in the suture line
FIGURE 5. After the periosteal graft is firmly anchored and sealed with fibrin glue, the autologous chondrocytes are introduced into the defect.
is left open to allow for injection of the cultivated cells. Before injection of the cells, the periphery of the periosteal graft is sealed using a fibrin sealant (Tisseel; Immuno AG, Vienna, Austria). Saline solution is then injected under the patch to assess for any leaks, and then the saline is removed. Finally, the cultured autologous chondrocytes are injected into the defect using a 1-mL syringe with a blunt tip plastic 18-gauge angiocatheter (Fig 5). Careful attention should be paid to an equal distribution of the cells throughout the entire defect. The remaining gap is closed using No. 6-0 Vicryl suture and a final layer of Tisseel is applied. The wound is gently irrigated. Careful attention to anatomic fixation of the osteotomized bone cannot be overemphasized as contact pressure studies have demonstrated that even minimal articular cartilage discontinuity can significantly alter the biomechanics and kinematics of the ankle joint.23 If lateral ankle stabilization is needed, it is the last procedure to be performed and is described below. The Sandwich Technique For OCD lesions that violate the subchondral layer, the standard technique for ACI will not be adequate. Peterson et al. described a technique used in the knee in which bone graft is placed in the base of the defect, and then two layers of periosteum are attached such that the cells are injected in between the periosteal layers in a “sandwich” fashion (Fig 6). These same principles are applied to the ankle and the important technical details of the procedure are as follows:
FIGURE 4. Placement of the periosteal graft over the talar defect with peripheral sutures holding the graft in place.
1. The bed of the lesion is curetted down to healthy cancellous bone, followed by drilling of the base to stimulate bleeding into the grafted area.
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oriented with the cambium layer facing towards the defect. Injection of the chondrocytes in between the two periosteal grafts and final sealing of the periphery of the graft is identical to the protocol described above. Combined Procedure: ACI and Lateral Ligament Complex Reconstruction If the patient has chronic ankle instability and would benefit from lateral ligament reconstruction, then this is carried out in conjunction with the ACI procedure. If the patient has an OCD in the anterolateral aspect of the talus, the ACI procedure and the lateral ligament reconstruction can be performed via the same anterolateral incision without the need for osteotomy. However, if the OCD lesion is located anywhere else on the talus, then osteotomy is indicated. We prefer the modified Brostrum technique using suture anchors in the distal fibula to anatomically reconstruct the anterior talofibular and calcaneofibular ligaments. Postoperative Care
FIGURE 6. The sandwich technique (A) Preparation and drilling of the base of the lesion. (B) Placement of autologous bone graft into the defect, not extending above the subchondral line. Placement of deep periosteal graft. (C) Fixation of the outer periosteal graft. Injection of chondrocytes in between the two periosteal grafts.
Postoperatively we keep our patients in the hospital for 48 hours. Standard postoperative antibiotics are administered for 24 hours. Continuous passive motion (CPM) is initiated 8 hours postoperatively with the parameters outlined in the section below. The patients are instructed to wear thromboembolic stockings for 10 days to improve venous return. Sutures are removed 1 week after discharge from the hospital. REHABILITATION Phase I: The Healing Phase (Weeks 0-6)
2. Autogenous cancellous bone graft taken from the distal tibia is placed into the defect, extending up to the level of the subchondral bone but not beyond. Firm tamping of the bone graft is important to prevent dislodgement. 3. Stable fixation of the deep periosteal graft is imperative. The graft is held in place at the level of the subchondral bone with multiple sutures at the periphery of the defect. Suture anchors can be helpful in lesions located at the far periphery of the talus. The graft should be placed such that the cambium layer is facing away from the defect. 4. Placement of the top periosteal graft is exactly the same as a routine ACI procedure, again,
The implanted chondrocytes are in the early stages of healing and are highly vulnerable to shear stresses during this phase. However, basic science studies have demonstrated that chondrocytes quickly atrophy without exposure to joint motion and load bearing compressive forces.24 Therefore, a balance between these risks must be achieved. We advocate early gentle range of motion exercises and minimal load bearing compressive forces while minimizing the shear and large compressive forces being exposed to the graft site. We allow for toe-touch weight bearing during the first 2 weeks and progressively increase to 75% weight bearing at the end of 6 weeks. Postoperatively, the patient is placed in a hinged ankle brace with the limits set between 10° dorsiflexion and 10° plantar-
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flexion. We start CPM exercises 8 hours postoperatively. The CPM machine is used during the first 2 weeks only. At 4 weeks, the patient is allowed to peform stationary bike activities without resistance. During the first 6 weeks, the range of motion exercises and brace parameters are gradually increased. The goal is to achieve full range of motion by 6 weeks. At approximately the 6-week mark, the patient can be weaned from the brace. Physical therapy during phase I focuses on proprioceptive exercises, isometric contractions of the ankle dorsiflexors and plantarflexors, quadriceps and hamstring training, and toe flexor and extensor exercises. In addition to the cycling, other recommended low-impact activites can include swimming and aquatic exercises. Phase II: The Transitional Phase (Weeks 6-12) During this phase, the chondrocyte implant begins to mature and is less vulnerable to shear forces, but graft healing is still incomplete. Grossly, the cartilage appears compressible and spongy, and is durable enough to tolerate increased compressive forces. Therefore, the weight bearing should progressively increase to eventual full weight bearing by week 8. Ankle range of motion should be progressively increased. The brace can be weaned when full range of motion is achieved, usually around the 6 to 8 week mark. Strengthening exercises can begin on a progressive basis, concentrating specifically on the gastroc-soleus complex as well as the ankle dorsiflexors, hamstrings, and quadriceps. The strengthening exercises should mostly be eccentric and closed-chain presses. The stationary bicycle should be continued with resistance added gradually. The goal is to not only prepare the ankle for the next phase in rehabilitation, but the entire body so that other injuries do not occur on resumption of sporting activities. Phase III: The Remodeling Phase (Weeks 12-32) Grossly, the graft becomes firm with a consistency of soft plastic. The matrix continues to mature and is ready for more vigorous activities. Walking distance and speed can now increase on a progressive basis. By the fifth to sixth month, a very gradual return to jogging and running can be performed. By the sixth month, increases in strength training and physical therapy should be complemented with cross training and a reintroduction to light sport-specific activities.25
Phase IV: The Maturation Phase (Months 8-12) The graft continues to remodel and can still be metabolically active for up to 12 to 15 months. However, by 8 months the graft is mature enough to tolerate the stresses of sporting activities without significant deleterious effects. A progressive return to the athlete’s sport can now be the main focus of rehabilitation. The idea of cyclical progression cannot be overemphasized for these athletes being reintroduced into their respective sport; increases in strength and training followed by periods of rest. Adherence to the above timeline allows for the graft to slowly mature while not compromising strength and range of motion, thus giving the patient the optimal chance at progressing up the chondropenia curve. We have found that it is quite helpful to work with a particular therapist who is familiar with ACI procedures and can provide frequent progress reports. Because this procedure is performed relatively infrequently, it is worthwhile to designate a single therapist who is familiar with this type of problem and is aware of the potential complications and pitfalls. Sending the therapist to a workshop or training session on ACI procedures and rehabilitation is strongly suggested. DISCUSSION Chondral and osteochondral lesions of the talus are challenging problems for the orthopaedist. Conservative treatment should be the mainstay of initial treatment. However, Jurgenson et al. reported that 37.5% of the patients who underwent conservative treatment eventually required surgery for continued symptoms.14 But even in OCD lesions refractory to conservative treatment, surgical intervention has not yielded consistent, reliable outcomes and has been largely disappointing in returning the patient to a functional, pain-free status. Struijs et al. recently reported the results of a large metanalysis looking at the results of treatment for OCD lesions of the talus and found good or excellent results in only 45% of the patients.26 The effectiveness of techniques that involve penetration of the subchondral plate in an attempt to allow stem cell migration from the marrow cavity into the defect has been well reported in the literature. These surgical techniques include subchondral drilling, microfracture, fragment excision and curettage, and microabrasion. Despite reports of good clinical results, it should be noted that none of these studies were able to demonstrate hyaline or hyaline like cartilage in the histological analysis of the treated lesions. Other tech-
AUTOLOGOUS CHONDROCYTE IMPLANTATION OF THE TALUS niques include internal fixation devices and various bone grafting techniques. Few randomized comparative studies for any of these treatment modalities exist in the literature. Roberts et al. reported excellent results in 56% of the patients with loose osteochondral fragments treated with metallic or bioabsorbable fixation screws.27 Ritzler and Van Dijk reported good or excellent results in 81% of patients treated with subchondral drilling.18 Other authors report success rates of between 51% and 88% using a variety of drilling techniques including both transmalleolar and retrograde applications.28-30 Overall, fair results have been reported with curettage, with and without bone grafting.31 The marginal results of the above referenced studies prompted the search for alternative resurfacing techniques in hopes of finding a technique that would provide better functional outcomes and prevent early joint degeneration. Early reports of good results using articular cartilage transplantation techniques in the knee prompted clinicians to experiment with these types of procedures in the talus. Two recent reports by Hangody et al. reviewed their results utilizing the mosaicplasty technique for treating OCD lesions of the talus. The procedure was performed on 36 patients with 2- to 7-year follow-up. Good or excellent results were reported in 94% of the patients. Donor site knee pain and painful hemarthrosis were the most common complaints with a total morbidity rate of 3%.32,33 Al-Shaikh et al. reported on 19 patients who underwent an osteochondral autograft transfer system (OATS) type of procedure for OCD lesions of the talus. With a mean follow-up of 16 months, the average AOFAS score was 91, with a reported incidence of donor site knee pain of 10.5%.34 In a similar study by Schottle et al., 39 patients had an overall improvement in Lysholm scores from 62 preoperatively to 92 postoperatively and a complication rate of 12%.35 Only one study exists at this time in which a fresh allograft osteochondral transplantation procedure was utilized for treatment of talar osteochondral defects. In this study, a total of 9 patients underwent this procedure with a 66% survival rate after a mean follow-up of 11 years. Arthrodesis was required in the 3 failures; the mechanism of failure was reportedly graft fragmentation and resorption, not arthritic degeneration.36 With the promising results of chondrocyte implantation techniques in the knee, clinicians embarked on the application of this procedure for chondral and osteochondral defects of the talus. Only 2 reports currently exist in the literature specifically addressing
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this topic. Giannini et al. was the first to report on a series of 8 patients with OCD lesions of the talus who had failed conservative nonoperative treatment, and subsequently underwent the ACI procedure.37 Overall AOFAS ankle scores improved from 32 points preoperatively to 91 points at 2-year follow-up. All patients had second-look arthroscopy and underwent biopsy of the graft site. Immunohistochemistry studies showed evidence of hyaline-like tissue in each patient, with an increase in cellularity and unequivocal evidence that type II collagen was present. Although encouraging, it is difficult to draw major conclusions from this study as the number of patients is inadequate to achieve clinical significance regarding the efficacy of this procedure. Additionally, the patients enrolled in this study had not undergone previous surgical intervention. The next study reported on ACI of the talus was performed by Koulalis et al. in 2002.5 In this study, a total of 8 patients were enrolled, each with talar OCD lesions refractory to conservative treatment. Average lesion size was 14 ⫻ 12 mm, and average depth of 7 mm. Significant improvement was reported as per Finsen ankle scores. The average follow-up up was 17.6 months. Second-look arthroscopy was performed in 3 patients at the 6-month postoperative mark and each showed complete coverage of the defect with a cartilage like substance, however the articular cartilage margin revealed a step-off of approximately 1 mm. Biopsy examination of the implant site was performed in only one patient. Histologic analysis revealed the presence of a fibrocartilage and immunohistochemistry staining showed formation of connective tissue with cartilaginous metaplasia, but failed to show the presence of type II collagen. All of the patients resumed their premorbid levels of work and leisure activities. Again, the clinical results appear to be good, but larger numbers are needed to validate the conclusions. Recently Brittberg and Peterson presented on a series of 14 patients treated with autologous chondrocyte grafting techniques for refractory chondral and osteochondral lesions of the talus.38 The mean follow-up was 32.4 months and mean lesion size was 1.7 cm2. Four patients underwent concomitant lateral ligamentous stabilization. Finsen ankle scores showed significant improvement in pain relief, walking, and activity levels. Overall, 79% of the patients improved and 21% were deemed poor. Half of the patients required second-look arthroscopy with each of the patients exhibiting graft hypertrophy secondary to overgrowth of the periosteal cover and were treated
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successfully with simple debridement. This represents the largest study to date with the longest average follow-up. Overall, the preliminary studies looking at ACI procedures for chondral and osteochondral lesions of the talus appear to be promising. The main indications are for patients who have failed both conservative treatment and initial attempts at surgical resurfacing. Currently, the chondrocyte implantation procedure requires at least a formal arthrotomy and, in most cases, a malleolar osteotomy as well. Although the complications are few, the most commonly reported problems in ACI patients are periosteal graft hypertrophy and osteotomy issues. The future of ACI procedures in general lies in the development of an implantation technique that ideally can be performed arthroscopically, thus eliminating the need for periosteal grafts and osteotomies altogether. Currently, work is being done on a biological scaffold impregnated with autologous chondrocytes.39 A preliminary study looking at a series of 67 patients using a hyaluronan-based biological scaffold as the chondrocyte carrier has recently been reported with good early results. Another study was recently published in which ACI was performed entirely arthroscopically using a resorbable polymer fleece scaffold with good preliminary results.40
5. 6. 7. 8. 9. 10. 11. 12. 13.
14. 15. 16. 17.
CONCLUSIONS In summary, we feel that ACI is a viable alternative when treating chondral and osteochondral lesions of the talus that are refractory to traditional modes of treatment. Although the early studies are promising, future prospective comparative studies are needed to validate the efficacy of this technique. In the future, technical improvements in the biological scaffold and chondrocyte delivery system will make arthroscopic implantation possible, diminishing the morbidity associated with arthrotomy and osteotomy.
18. 19. 20. 21. 22.
23.
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24.
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AUTOLOGOUS CHONDROCYTE IMPLANTATION OF THE TALUS 29. Conti SF, Taranow WS. Transtalar retrograde drilling of medial osteochondral lesions of the talar dome. Oper Tech Orthop 1996;6:226-230. 30. Baker CL, Andrews JR, Ryan JB. Arthroscopic treatment of transchondral talar dome fractures. Arthoscopy 1986;2:82-87. 31. Angermann P, Jensen P. Osteochondritis dissecans of the talus: Long term results of surgical treatment. Foot Ankle 1989;10:161-163. 32. Hangody L, Fules P. Autologous osteochondral mosaicplasty for the treatment of full thickness defects of weight-bearing joints: Ten years of experimental and clinical experience. J Bone Joint Surg Am 2003;85:25-32. 33. Hangody L, Kish G, Karpati Z, Modis L, Szerb I, Gaspar L, Dioszegi Z, Kendik Z. Mosaicplasty for the treatment of osteochondritis dissecans of the talus: Two to seven year results in 36 patients. Foot Ankle Int 2001;22:552-558. 34. Al-Shaikh RA, Chou LB, Mann JA, Dreeben SM, Prieskorn D. Autologous osteochondral grafting for talar carilage defects. Foot Ankle Int 2002;23:381-390. 35. Schottle PB, Oettl GM, Agneskirchner JD, Imhoff AB. Operative therapy of osteochondral lesions of the talus with autol-
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ogous cartilage-bone transplantation. Orthopaedica 2001;30: 53-58. Gross AE, Agnidis Z, Hutchison CR. Ostochondral defects of the talus treated with fresh osteochondral allograft transplantation. Foot Ankle Int 2001;22:385-391. Giannini S, Buda R, Grigolo B, Vannini F. Autologous chondrocyte transplantation in osteochondral lesions of the ankle joint. Foot Ankle Int 2001;22:513-517. Brittberg M, Lindahl A, Sjogren-Jansson E, Peterson L. Chondral and osteochondral ankle lesions treated with autologous chondrocyte grafting technique. Personal communication, 2003. Pavesio A, Abatangelo G, Borrione A, Brocchetta D, Hollander AP, Kon E, Torasso, F, Zanasi S, Marcacci M. Hyaluronan-based scaffolds (Hyalograft C) in the treatment of knee cartilage defects: Preliminary clinical findings. Novartis Foundation Syposium 2003;249:203-217, discussion 229-241. Erggelet C, Sittinger M, Lahm A. The arthroscopic implantation of autologous chondrocytes for the treatment of fullthickness cartilage defects of the knee joint. Arthroscopy 2003; 19:108-110.