Autologous matrix-induced chondrogenesis for management of osteo-chondral lesions of the talus: A pilot study

INTRODUCTION

Forces and body weight are transferred between the lower leg and the foot by the talus bone. Approximately 70% of ankle injuries can result in different degrees of talar chondral and osteochondral injuries.^[1]

Both isolated and coupled talar injuries can occur, and clinicians need to be aware of their potential long-term and clinical consequences. Osteo-chondral lesion (OCL) of the talus, if unrecognized and inadequately treated, may result in secondary osteoarthritis, accompanied by discomfort and functional impairment.^[2-4]

OCL of the talus is an acquired idiopathic lesion of the subchondral bone that may or may not cause instability and articular cartilage involvement, as well as delamination and sequestration. The most well-established cause of OCL of the talus is recurrent microtraumas linked to vascular damage, which results in increasing ankle dysfunction and discomfort.^[5]

The classification of OCL of the talus plays a key role in guiding diagnosis, treatment planning, and prognosis. Several systems have been developed over time, utilizing radiographic, computed tomography (CT), and magnetic resonance imaging (MRI) modalities. These classifications aim to evaluate the lesion’s size, location, and stability, while assisting in the selection of the most suitable management strategy.^[6]

The Berndt and Harty radiographic classification, first proposed in 1959, categorizes OCL of the talus into four stages: Stage I: Subchondral bone compression without fracture.^[7] Stage II: A slightly separated osteo-chondral fragment with an intact cartilage cap. Stage III: A totally separated but undisplaced fragment. Stage IV: A dislocated piece of osteo-chondral fragment within the joint.

The Ferkel and Sgaglione classification, introduced in the 1990s, expanded on the Berndt and Harty system by utilizing CT imaging.^[8] It categorizes OCL of the talus into five stages: Stage A: Subchondral cyst without fracture. Stage B: Subchondral bone flattening with intact cartilage. Stage C: Non-displaced osteo-chondral fragment. Stage D: Displaced osteo-chondral fragments. Stage E: Subchondral bone cyst or osteonecrosis with significant joint involvement.

The Hepple classification (MRI-based staging), developed in 1999, comprises six stages: Stage I: involves articular cartilage damage with subchondral bone edema (also known as a bone bruise).^[9] Stage IIa: Subchondral cyst formation with intact cartilage. Stage IIb: Subchondral cyst with articular cartilage breach. Stage III: Detached but undisplaced osteochondral fragment with adjacent subchondral cyst. Stage IV: Displaced osteochondral fragment. Stage V: Subchondral cystic changes and extensive osteonecrosis. MRI is regarded as the gold standard for evaluating OCL of the talus, as it provides detailed information about cartilage, subchondral bone, and surrounding soft tissues.^[9]

OCL of the talus has been challenging to manage because articular cartilage has a poor healing capacity due to its lack of vessels, nerve supply, and isolation from systemic regulation.^[10]

Although conservative treatment is the primary choice of treatment, especially for small, stable, and non-displaced lesions, surgery is required, especially for larger and more severe defects, and especially for young patients with unstable cartilage fragments. The goals of surgical treatment include restoring cartilage, filling in the deficiency, repairing the articular surface, and halting the progression of osteoarthritis. There are various surgical options: including bone marrow stimulation techniques such as drilling or microfractures are appropriate for small lesions <150 mm², debridement of the necrotic subchondral bone, internal fixation of the fragment or its removal followed by debridement of the crater, or tissue transplantation techniques such as osteochondral auto or allograft, or several smaller osteochondral blocks (mosaicplasty), autologous chondrocyte implantation (ACI), and matrix-induced ACI (MACI).^[3,5,10-12]

Alternative techniques are required to fix the OCL of the talus. The autologous matrix-induced chondrogenesis (AMIC) procedure addresses this requirement by overcoming the drawbacks of alternative repair techniques, which include compromising healthy cartilage, requiring multiple-stage operations, being expensive, and having limited transplant availability. It was initially reported by Benthien and Behrens^[13] who employed a collagen type I/III bilayer matrix to enhance proteoglycan deposition through the chondrogenic differentiation of human mesenchymal stem cells, thereby solidifying the super clot on top of the lesion following micro-fracture.^[14,15]

This study aimed to evaluate the clinical and functional outcome of using the AMIC technique for the surgical management of patients with OCL of the talus.

MATERIALS AND METHODS

Pre-operative evaluation

Every patient had a thorough general checkup and full medical history, regarding age, sex, occupation, side involved, duration of symptoms, history of trauma, and, if present, how it was managed, level of activity, presence of giving way or locking manifestations before they were recruited.

All patients underwent a local physical examination for tenderness, range of motion (ROM), instability, malalignment, ability to walk, and neurovascular examination. The visual analog scale (VAS)^[16] score and American Orthopedic Foot and Ankle Society (AOFAS)^[17] score were utilized to evaluate patients’ symptoms, pain, foot and ankle function, ROM, and patients’ satisfaction after operation.

Radiological evaluation including plain radiographs anteroposterior and lateral weight-bearing views of both ankles [Figure 1A and B], stress views for detecting instability, CT ankle [Figure 1C and D], magnetic resonance images (MRI) [Figure 1E and F] of the affected ankle to evaluate lesion site, size, containment, cartilage surface, subchondral bone condition and the condition of the opposite cartilage to diagnose kissing ulcer, lesion length (in the coronal or axial images), lesion width (in the sagittal and axial images), lesion depth (vertical extension in the coronal and sagittal images), and the defect area was calculated by ellipse formula (coronal length × sagittal length × 0.79).

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Figure 1:

Radiograph of ankle (A) anteroposterior and (B) lateral views shows an osteochondral lesion at the talus, located at the superior medial part. Computed tomography ankle (C) coronal and (D) sagittal views show an osteochondral lesion at the talus. Magnetic resonance images of the ankle, (E) coronal and (F) sagittal views, show an osteochondral lesion in the talus. The black arrows in Figure 1 (A-F) indicate the osteochondral lesion (OCL) of the talus.

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The lesions were classified as: Small <150 mm² or large > 150 mm² by CT and MRI evaluation and confirmed by arthroscopy, medial or lateral, and non-contained defect, which did not have a surrounding cartilage border on each side, or contained defect, which has surrounding articular cartilage, and the cartilage surface is intact or not.

Before surgery, all patients underwent a standard evaluation process that included laboratory testing, consultation with cardiologists and chest physicians as needed, and consultation with anesthesia specialists to determine their surgical suitability and obtain their informed consent.

Surgical techniques include

1-Technique of arthroscopic debridement

Arthroscopy was initially performed for diagnostic assessment of the size, location of the lesion, cartilage quality, to exclude associated intra-articular lesions (loose bodies or synovitis), debridement, and evaluation of the lateral ligaments, especially the anterior talo-fibular ligament, before converting to an open approach.

Twenty-two patients underwent diagnostic ankle arthroscopy before undergoing either an open medial malleolar osteotomy or an open arthrotomy.

This step guided the surgical plan and ensured precise localization of the defect.

All patients were positioned in a supine position. The surgery was carried out under spinal anesthesia or ultrasound-guided regional nerve block anesthesia for the sciatic and femoral nerves. Antibiotics were administered intravenously as prophylaxis to all patients, and a pneumatic tourniquet was utilized.

Plantar flexing the ankle and fourth toe allowed for the identification of the superficial peroneal nerve. Joint distension was done by injecting 20 mL of saline. Blunt dissection proceeded through the capsule into the ankle joint after a superficial skin incision. With the ankle dorsiflexed, standard anteromedial portals were created at the joint line, 1 cm proximal to the medial malleolus tip, and just medial to the anterior tibial tendon. After that, the anterolateral portal was completed just lateral to the peroneus tertius tendon and at the same level as the joint [Figure 2A].

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Figure 2:

(A) Standard visualization and working portal of ankle arthroscope and (B) probing the osteochondral lesion of the talus.

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Depending on the medial or lateral location and extent of the lesion, the arthroscope was moved to the opposite portal to facilitate visualization and access (switching the portals).

The joint was then thoroughly evaluated for any associated articular pathology [Figure 2B]. Loose bodies within the joint were identified and removed, and all dead bone and overlying unstable cartilage were removed using an arthroscopic shaver and curettes till reaching stable cartilage.

2-Technique of AMIC

The surgical approach of the arthrotomy depends on the location of the defect. For postero-medial lesions, an osteotomy of the medial malleolus [Figure 3A] was done, and directed antero-medially with careful retraction to protect the tibialis posterior tendon. It was fixed at the end of the procedure using 2 partially threaded 4.0 mm cannulated screws and previous drilling before osteotomy was done to avoid displacement of the fracture [Figure 3A]. Open arthrotomy was used to treat the lesions on the lateral side.

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Figure 3:

(A) Medial malleolus osteotomy. (B) Autologous matrix-induced chondrogenesis membrane. (C) Autologous matrix-induced chondrogenesis membrane application in osteochondral lesions of the talus. (D) Fixation of the membrane by fibrin glue.

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Following medial malleolus osteotomy, OCL of the talus was addressed, debridement and removal of unhealthy friable cartilage were done, and the defect was prepared by removal of subchondral weak bone till healthy bone was obtained. Perforation of the sclerotic sub-chondral bone was done using a 2 mm Kirschner wire. The initial arthroscopic debridement was diagnostic and limited to unstable cartilage flaps to assess lesion extent.

After performing the medial malleolar osteotomy, definitive debridement and defect preparation were completed under direct visualization to reach healthy subchondral bone.

The matrix [Figure 3B] is a bilayer membrane composed of one compact and one porous side, made up of collagen types I and III (Chondro-Gide). The smooth-surfaced, compact membrane layer is cell-occlusive, shielding the bone marrow cells that follow drilling from mechanical impact and inhibiting their diffusion into the synovial fluid. Collagen fibers are arranged loosely and porously in the other membrane layer, which promotes cell invasion and adhesion. The mesenchymal stem cells are stimulated to differentiate into the chondrocyte phenotype by the collagen matrix. The collagen membrane provides a three-dimensional scaffold that stabilizes the bone marrow clot and supports the migration and differentiation of marrow-derived mesenchymal cells into chondrocyte-like cells.

To avoid delamination of the matrix, the defect was filled only to the level of the subchondral bone by graft from the calcaneus, the iliac bone, or an allograft. The defect was measured and templated using a sterile aluminum sheet, and the collagen membrane was then cut to match the defect [Figure 3C]. Finally, cover the graft with the collagen membrane and secure it in place using fibrin glue [Figure 3D].

The matrix overlaps with adjacent cartilage were avoided to prevent delamination of the matrix on joint movement. Multiple sagittal ankle movements were then performed to verify the stability of the implant. Then fixation of the medial malleolous osteotomy by cannulated screws was done. Then, the wound was closed in layers. Dressings were applied, and a below-knee slab was made.

Post-operative follow-up

Radiographs taken immediately after surgery. In the outpatient clinic, follow-up radiographs [Figure 4A and B] were routinely collected at 3, 6, 12 weeks, and 6 and 12 months to monitor the healing of OCL of the talus. Immobilization in a below-knee slab immediately after surgery and changed to an ankle foot orthosis 2 weeks later, and began passive ROM exercises for the knee and ankle. After 8 to 12 weeks of non-weight-bearing, patients were allowed to resume full weight-bearing once radiographs indicated that bone healing had occured. After 6 months, patients were permitted to resume their athletic activities. MRI [Figures 4C and D] was performed 6–12 months after the procedure to confirm the healing of the lesion. Pain and functional outcomes were assessed with the VAS scale and AOFAS scoring system 6 months postoperatively.

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Figure 4:

One-year post-operative radiograph of ankle (A) anteroposterior and (B) lateral views show complete union of the medial malleolus osteotomy site and osteochondral lesion at the talus, located at the superior medial part. Magnetic resonance images of the ankle, 1-year post-operative, (C) sagittal and (D) coronal views, show healing, incorporation, and complete filling of the defect associated with osteochondral lesion in the talus.

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RESULTS

The present study reveals a mean age of 35.96 ± 11.91 years. Sixty percentages of the patients were male, and 40% were female. The mean body mass index was 27.67 ± 4.44 kg/m. Regarding occupation, employees (33.3%) and manual workers (30%) made up the largest segments, followed by housewives (20%) and students (16.7%). Seventeen patients developed the lesion on the left side (56.7%), and 13 patients developed the lesion on the right side (43.3%) [Table 1].

The mean duration of symptoms was 2.07 ± 1.18 years. Notably, 40% had undergone previous surgery, which may suggest either complex or recurrent pathology requiring multiple interventions. In terms of lifestyle factors, 36.7% of the patients were smokers, and the majority (63.3%) were non-smokers [Table 1]. The mean follow-up period was 12.6 months (range, 6–20 months).

The mean surface area of the lesion was 168.16 ± 25.85 mm² (127–225 mm²), it is classified based on size into: Small size lesions (<1.5 cm²): Including six cases with previous history of drilling without improvement and large size lesions (≥1.5 cm²): Including 24 cases indicating a moderate variation in lesion size across the sample. In terms of injury mechanism, 33.3% reported no trauma, suggesting a possible degenerative or overuse etiology. Among trauma-related cases, twisting ankle injuries (20%) and ankle sprains (26.7%) were most common, highlighting the relevance of rotational forces and ligamentous injuries in lesion development. A smaller proportion reported previous fractures (13.3%) or falls (6.7%), representing higher-energy trauma [Table 1].

The VAS score, measuring pain intensity, showed a substantial reduction from 6.40 ± 1.27 preoperatively to 2.13 ± 1.27 postoperatively, with a mean change of –4.27 ± 1.80 (P < 0.001), indicating a highly significant decrease in pain levels. In addition, the AOFAS score, which reflects ankle function, increased from 49.10 ± 10.62 to 80.13 ± 10.25, with a mean improvement of 31.03 ± 14.76 (P < 0.001), demonstrating marked functional recovery. These findings underscore the effectiveness of surgical intervention in alleviating pain and enhancing mobility or daily function [Table 2]. An MRI was conducted at the 6–12-month follow-up to assess the repair tissue with the Magnetic Resonance Observation of Cartilage Repair Tissue scoring system, which yielded a mean score of 74.3 ± 8.5, signifying satisfactory cartilage repair in the majority of patients. MRI revealed acceptable integration with the nearby native cartilage, smooth surface continuity, and excellent defect filling. For the medial malleolar osteotomy, the average radiographic bone healing period was 10.5 ± 2.1 weeks.

The most common graft donor site was the iliac crest (53.3%), followed by the calcaneus (26.7%) and allografts (20%). Lesions were predominantly located on the posteromedial aspect of the ankle (70%). In terms of osteotomy, 73.4% of patients underwent a medial malleolus osteotomy, while 26.7% required no osteotomy [Table 3]. The mean operative time was 113 ± 23 min, while the mean tourniquet time was 103 ± 26 min.

Most patients returned to sports and high-impact activities with complete healing between 6 and 9 months postoperatively, contingent on their functional recovery and imaging findings that confirmed successful cartilage regeneration.

Regarding complications, 60% of patients experienced no complications. Among those with complications, the most common were non-union of the osteotomy site (3 cases, 10%), which was addressed by refreshing the bone edges and refixation. In addition, 3 cases (10%) had infection, which improved with antibiotics, followed by hematoma (6.7%), which also improved with medical treatment. Less frequent complications included painful hardware, wound dehiscence, resistant pain, and deep vein thrombosis, each affecting 3.3% of patients. Finally, the complications reported in our study [Table 3] ranged between 1 and 3b according to the ClavienDindo classification.^[18]

DISCUSSION

The AMIC technique is an emerging one-step surgical technique designed to promote cartilage regeneration by combining microfracture with collagen I/III matrix to stabilize the clot and enhance healing.^[19]

Our study results demonstrated encouraging improvements in both clinical, radiological, and functional outcomes, further supporting the utility of AMIC as a viable one-step, regenerative surgical technique for challenging ankle cartilage lesions.

Demographically, the mean age of the studied patients was approximately 36 years, with a wide age range (17–56 years), reflecting the typical population affected by OCL of the talus, which is predominantly young to middle-aged, often active individuals. Males constituted the majority of the study group (60%), aligning with previous literature that reports a higher incidence of OCL of the talus in males.^[20,21]

Clinically, the chronic nature of the lesions was evident, with an average symptom duration exceeding 2 years, reinforcing the notion that OCLs are often underdiagnosed or mismanaged in the early stages. Notably, 40% of our patients had undergone previous surgical interventions; these results also align with those of Weigelt et al., who observed that many patients presented with longstanding symptoms and had previously undergone conservative treatments before receiving AMIC, emphasizing its role as a secondary or salvage procedure following failed initial interventions.^[22] Smoking prevalence (36.7%) is also of concern, given its known deleterious effects on cartilage healing and postoperative recovery.^[23]

Mechanically, trauma was implicated in most cases, with ankle sprains and twisting injuries being the most prevalent causes. Interestingly, one-third of the patients reported no clear history of trauma, pointing toward a possible role for subclinical microtrauma or intrinsic cartilage weaknesses, including vascular insufficiency or genetic predispositions. Lesion size averaged 168 mm², consistent with the indication threshold (>1.5 cm²) where AMIC is favored over simpler marrow-stimulation techniques. Malahias et al. reported that although trauma is a frequent etiological factor, non-traumatic causes such as vascular insufficiency or congenital factors may also play a role.^[24] Their review further confirmed that a lesion size >1.5 cm² is a critical threshold, where AMIC demonstrates favorable outcomes over marrow stimulation techniques, aligning with the lesion characteristics observed in the current study.

Functionally and symptomatically, the post-AMIC results were highly promising. There was a significant improvement in VAS pain scores and AOFAS functional scores, underscoring both pain relief and restoration of mobility. These findings are in concordance with Migliorini et al.,^[25] who reported significant improvements in VAS pain scores and AOFAS functional scores across 778 patients, confirming the procedure’s efficacy in reducing pain and restoring joint function over a mean follow-up of 37.4 months.

Surgically, the iliac crest was the most common donor site for cancellous bone grafts (53.3%), preferred for its rich marrow content and ease of harvest. Lesions were predominantly located posteromedially (70%), a finding that reflects the high vulnerability of this zone due to impaction and torsional forces during injury. Most patients required osteotomies, especially medial malleolar to access deep lesions, which, while technically demanding, were managed effectively in most cases.

Complication rates were average, with 60% of patients having uneventful recoveries. The most notable complications included non-union (10%) and infections (10%), both of which are manageable with early detection and intervention. Minor issues such as hardware-related discomfort and hematomas were relatively rare. These outcomes are consistent with the literature describing AMIC as a safe technique with a favorable risk-benefit profile, as noted by a study of Weigelt et al, who reported no failures and found that although 58% of patients required reoperation, it was mainly for hardware removal, not due to AMIC failure, confirming the procedure’s overall safety and effectiveness.^[22]

Reduced soft-tissue dissection, a minimally invasive approach, relying more on arthrotomy than osteotomy, minimizing the size of the osteotomy if at all possible, ensuring anatomical reduction of the osteotomy, encouraging protected weight bearing until radiological union, improving wound care, and careful patient selection are some suggested protocols that may improve the outcome.

A systematic review by Migliorini et al.^[26] reported that chondral defects of the talus that fail conservative management may require surgical intervention. Microfracture is typically reserved for small lesions, whereas AMIC and MACI are applied to larger defects. Furthermore, they noted that AMIC and MACI provide comparable midterm outcomes in managing focal talar chondral defects, with no significant differences in ROM or complication rates. However, AMIC offers key advantages: it is a single-stage procedure, eliminates the need for tissue harvesting, reduces morbidity and recovery time, avoids cell culture requirements, and lowers hospitalization costs. By utilizing subchondral bone marrow mesenchymal stem cells for regeneration, AMIC presents a particularly appealing option for both patients and surgeons.

Walther et al.^[27] reviewed 15 studies (492 patients) and conducted a meta-analysis of 12 studies (323 patients) on AMIC for talar OCLs. They reported significant improvements in pain and functional outcomes across all studies, with these benefits maintained throughout the follow-up period. Long-term data confirmed sustained symptom relief, functional stability at 5 years, and successful return to sports.

The lack of a control group and the small sample size of our study pose limitations, which are due to the rarity of the lesion, a phenomenon also noted in other studies, as well as our single-center design and brief follow-up duration.

CONCLUSION

The AMIC technique for managing OCL of the talus has demonstrated significant clinical and functional improvement in patients. It proved to be a secure and efficient option, especially for patients with medium to large lesions who had failed conservative or previous surgical interventions. Despite some manageable complications, the overall outcomes affirm the AMIC technique as a promising single-step cartilage repair strategy that preserves joint integrity and supports early functional recovery.