Matrix-associated Chondrocyte Implantation Research Articles

Surgical Approach to Full Thickness Cartilage Defect With Patellar Instability: Combined Matrix-Associated Chondrocyte Implantation (MACI) and Medial Patellofemoral Ligament (MPFL) Reconstruction

Background: Cartilage injury in the setting of acute patellar dislocation is a devastating condition that can lead to decreased quality of life and can progress to early osteoarthritis of the knee if not treated adequately. Indications: Matric-associated chondrocyte implantation (MACI) with concomitant medial patellofemoral ligament reconstruction (MPFLR) is indicated for young, high-demand patients with a symptomatic, full-thickness chondral lesions >2 cm2 that have failed an initial trial of conservative management or are found to have evidence of extensive cartilage damage or loose body that is not amenable to fixation. Technique Description: The MACI technique requires a 2-stage procedure. An initial diagnostic arthroscopy aids in characterization of the chondral lesion with regard to lesion size, depth, and morphology. Hyaline cartilage was harvested and autologous chondrocytes are seeded onto a MACI scaffold to grow. At the second stage, an MPFLR is planned alongside MACI. First a midline incision is made. Notably, instead of performing the capsulotomy at this stage, we proceed with the dissection for the MPFLR first creating a plane between layer #2 and #3 for easier graft retrieval later. The defect site is prepared, and the MACI graft is seated in the defect and secured. Medial patellofemoral ligament reconstruction is then begun by fixing the preloaded semitendinosus allograft to the patella. Shottle point is confirmed via fluoroscopy and dissection down to the femoral condyle is performed. The graft is retrieved between the 2 layers that were dissected earlier in the procedure and fixed within the femoral tunnel. Finally, the synovial layer is closed deep to the MPFL graft and the vastus medialis oblique (VMO) layer is closed superficial to it before closing the wound in the standard fashion. Results: The MACI procedure demonstrates high rates of satisfaction for relief of pain and significant improvements in clinical outcomes with generally low incidence of complications. Matric-associated chondrocyte implantation has been shown to be superior to microfracture in the treatment of larger (>3 cm2) symptomatic articular defects at 5 years. Discussion/Conclusion: Matric-associated chondrocyte implantation procedure with concomitant MPFLR should be considered in indicated patients with full thickness cartilage defects that are not amenable to fixation. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Autologous chondrocyte implantation for treatment of articular cartilage defects in the knee and ankle of football (soccer) players

BackgroundAutologous chondrocyte implantation (ACI) continues to evolve into one of the most efficient and common techniques for repair of articular cartilage defects. Significant progress has been made within the last decade regarding its application in the context of professional sports, such as football. This article provides a current overview of the application of ACI in the context of amateur and professional football. MethodsClinical studies involving football players and other high-impact sports athletes treated with ACI were reviewed. The scientific and technical development of ACI was evaluated considering latest publications, and analyzed for treatment outcome parameters. ResultsFootball players reported good to excellent results after treatment with ACI or matrix-associated chondrocyte implantation (MACI). Activity scores and clinical knee and ankle scores were significantly improved after surgery. Great advances have been made in surgery specific rehabilitation algorithms, leading to shorter return to play times. New surgical techniques have been introduced, reducing the 2-stage design of ACI to only one surgical intervention, accelerating return to play time further while reducing morbidity. ConclusionSurgical repair of focal articular cartilage defects via ACI in football players often provides successful return-to-competition and produces long lasting regeneration tissue, enabling players to continue their career on the pre-injury level of play. The technique itself is constantly evolving, addressing initial shortcomings and making it more widespread available to the recreational and professional athlete.

Long-term cost-effectiveness of matrix-associated chondrocyte implantation in the German health care system: a discrete event simulation

IntroductionCartilage defects in the knee can be caused by injury, various types of arthritis, or degeneration. As a long-term consequence of cartilage defects, osteoarthritis can develop over time, often leading to the need for a total knee replacement (TKR). The treatment alternatives of chondral defects include, among others, microfracture, and matrix-associated autologous chondrocyte implantation (M-ACI). The purpose of this study was to determine cost-effectiveness of M-ACI in Germany with available mid- and long-term outcome data, with special focus on the avoidance of TKR.Materials and methodsWe developed a discrete-event simulation (DES) that follows up individuals with cartilage defects of the knee over their lifetimes. The DES was conducted with a status-quo scenario in which M-ACI is available and a comparison scenario with no M-ACI available. The model included 10,000 patients with articular cartilage defects. We assumed Weibull distributions for short- and long-term effects for implant failures. Model outcomes were costs, number of TKRs, and quality-adjusted life years (QALYs). All analyses were performed from the perspective of the German statutory health insurance.ResultsThe majority of patients was under 45 years old, with defect sizes between 2 and 7 cm2 (mean: 4.5 cm2); average modeled lifetime was 48 years. In the scenario without M-ACI, 26.4% of patients required a TKR over their lifetime. In the M-ACI scenario, this was the case in only 5.5% of cases. Thus, in the modeled cohort of 10,000 patients, 2700 TKRs, including revisions, could be avoided. Patients treated with M-ACI experienced improved quality of life (22.53 vs. 21.21 QALYs) at higher treatment-related costs (18,589 vs. 14,134 € /patient) compared to those treated without M-ACI, yielding an incremental cost‐effectiveness ratio (ICER) of 3376 € /QALY.ConclusionM-ACI is projected to be a highly cost‐effective treatment for chondral defects of the knee in the German healthcare setting.

Regenerative Potential of Platelet Concentrate Lysate in Mechanically Injured Cartilage and Matrix-Associated Chondrocyte Implantation In Vitro.

Adjuvant therapy in autologous chondrocyte implantation (ACI) can control the post-traumatic environment and guide graft maturation to support cartilage repair. To investigate both aspects, we examined potential chondro-regenerative effects of lysed platelet concentrate (PC) and supplementary interleukin 10 (IL-10) on mechanically injured cartilage and on clinically used ACI scaffolds. ACI remnants and human cartilage explants, which were applied to an uniaxial unconfined compression as injury model, were treated with human IL-10 and/or PC from thrombocyte concentrates. We analyzed nuclear blebbing/TUNEL, sGAG content, immunohistochemistry, and the expression of COL1A1, COL2A1, COL10A1, SOX9, and ACAN. Post-injuriously, PC was associated with less cell death, increased COL2A1 expression, and decreased COL10A1 expression and, interestingly, the combination with Il-10 or Il-10 alone had no additional effects, except on COL10A1, which was most effectively decreased by the combination of PC and Il-10. The expression of COL2A1 or SOX9 was statistically not modulated by these substances. In contrast, in chondrocytes in ACI grafts the combination of PC and IL-10 had the most pronounced effects on all parameters except ACAN. Thus, using adjuvants such as PC and IL-10, preferably in combination, is a promising strategy for enhancing repair and graft maturation of autologous transplanted chondrocytes after cartilage injury.

Surgical Treatment for Osteochondral Lesions of the Talus

AbstractOsteochondral lesions of the talus (OLT) are often associated with ankle pain and dysfunction. They can occur after ankle trauma, such as sprains or fractures, but they usually present as a continued ankle pain after the initial injury has resolved. Chronic ankle ligament instability and subsequent microtrauma may lead to insidious development of an OLT. Medial-sided lesions are more common (67%) than lateral-sided lesions. For acute lesions that are nondisplaced, nonoperative management is initially performed, with a 4-6 week period of immobilization and protected weight bearing. Symptomatic improvement results in more than 50% of patients by 3 months. Acute osteochondral talus fractures, which have a bone fragment thickness greater than 3 mm with displacement will benefit from early surgical intervention. These injuries should undergo primary repair via internal fixation with bioabsorbable compression screws 3.0 mm or smaller using at least 2 points of fixation. Acute lesions that are too small for fixation can be treated with morselization and reimplantation of the cartilage fragments. If OLTs are persistently symptomatic following an appropriate course of nonoperative treatment, various reparative and restorative surgical options may be considered on the basis of diameter, surface area, depth, and location of the lesion.A small subset of symptomatic osteochondral lesions of the talus involve subchondral pathology with intact overlying articular cartilage; in these cases, retrograde drilling into the cystic lesion can be employed to induce underlying bony healing. Cancellous bone graft augmentation may be used for subchondral cysts with volume greater than 100 mm3 or with those with a depth of more than 10 mm.Debridement, curettage, and bone marrow stimulation is a reparative technique that may be considered in lesions demonstrating a diameter less than 10 mm, with surface area less than 100 mm2, and a depth less than 5 mm. This technique is commonly performed arthroscopically using curettes and an arthroscopic shaver to remove surrounding unstable cartilage. A microfracture awl of 1 mm or less is used to puncture the subchondral bone with 3-4 mm of spacing between to induce punctate bleeding. Initial (<5 year) results are good to excellent in 80% of cases, with some deterioration of improvement over time. Factors contributing to poor results include surface area greater than 1.5 cm2, overall osteochondral lesion depth over 7.8 mm, smoking history, age over 40, and uncontained lesions.Lesions greater than 1.29 cm2, cystic lesions, and lesions that have failed prior treatment are potential candidates for osteochondral autograft transplantation. The autograft is typically harvested from the lateral femoral condyle of the ipsilateral knee with an optimal plug depth and diameter of 12-15 mm. Transplantation often involves open technique and may even require malleolar osteotomy for perpendicular access to the defect, as well as visualization of a flush, congruent graft fit. Good to excellent outcomes have been reported in up 87.4% of cases with the most common complication being donor site morbidity in up to 15% of cases. Failure rates increased significantly in lesions larger than 225 mm2.Scaffold-based therapies, such as matrix-associated chondrocyte implantation, can be employed in primary or revision settings in lesions larger than 1 cm2, including uncontained shoulder lesions with or without cysts. Lesions with greater than 4 mm of bone loss following debridement may require bone grafting to augment with the scaffold. This technique requires an initial procedure for chondrocyte harvest and a secondary procedure for transplantation of the scaffold. Outcomes have been good to excellent in up to 93% of cases; however, this technique requires a two-stage procedure and can be cost-prohibitive.Particulated juvenile cartilage is a restorative technique that employs cartilage allograft from juvenile donors. The cartilage is placed into the defect and secured with fibrin glue in a single-stage procedure. Studies have shown favorable outcomes in 92% of cases, with lesions between 10 and 15 mm in diameter, but increased failure rates and poorer outcomes in lesions larger than 15 mm. This may be an alternative option for contained lesions between 10 and 15 mm in diameter.Osteochondral allograft plugs are an option for larger contained lesions (>1.5 cm in diameter) and in patients with knee osteoarthritis (OA) and concern for donor site morbidity. Furthermore, bulk osteochondral allograft from a size-matched talus can also be used for even larger, unstable/uncontained shoulder lesions. An anterior approach is often employed and fixation is achieved via placement of countersunk headless compression screws.Failure of the aforementioned options associated with persistent pain or progressive OA would then lend consideration to ankle arthroplasty versus ankle arthrodesis.

Chondral Lesions of the Knee: An Evidence-Based Approach.

Management of chondral lesions of the knee is challenging and requires assessment of several factors including the size and location of the lesion, limb alignment and rotation, and the physical and mental health of the individual patient. There are a multitude of options to address chondral pathologies of the knee that allow individualized treatment for the specific needs and demands of the patient. Osteochondral autograft transfer remains a durable and predictable graft option in smaller lesions (<2 cm2) in the young and active patient population. Both mid-term and long-term results for large chondral lesions (≥3 cm2) of the knee have demonstrated favorable results with the use of osteochondral allograft or matrix-associated chondrocyte implantation. Treatment options for small lesions (<2 cm2) include osteochondral autograft transfer and marrow stimulation and/or microfracture with biologic adjunct, while larger lesions (≥2 cm2) are typically treated with osteochondral allograft transplantation, particulated juvenile articular cartilage, or matrix-associated chondrocyte implantation. Emerging technologies, such as allograft scaffolds and cryopreserved allograft, are being explored for different graft sources to address complex knee chondral pathology; however, further study is needed.

Cartilage T2 Relaxation Times and Subchondral Trabecular Bone Parameters Predict Morphological Outcome After Matrix-Associated Autologous Chondrocyte Implantation With Autologous Bone Grafting

Background: Quantitative magnetic resonance (MR) imaging techniques are established for evaluation of cartilage composition and trabecular bone microstructure at the knee. It remains unclear whether quantitative MR parameters predict the midterm morphological outcome after matrix-associated chondrocyte implantation (MACI) with autologous bone grafting (ABG). Purpose: To assess longitudinal changes and associations of the biochemical composition of cartilage repair tissue, the subchondral bone architecture, and morphological knee joint abnormalities on 3-T MR imaging after MACI with ABG at the knee. Study Design: Case series; Level of evidence, 4. Methods: Knees of 18 patients (28.7 ± 8.4 years [mean ± SD]; 5 women) were examined preoperatively and 3, 6, 12, and 24 months after MACI and ABG using 3-T MR imaging. Cartilage composition was assessed using T2 relaxation time measurements. Subchondral bone microstructure was quantified using a 3-dimensional phase-cycled balanced steady-state free precision sequence. Trabecular bone parameters were calculated using a dual threshold algorithm (apparent bone fraction, apparent trabecular number, and apparent trabecular separation). Morphological abnormalities were assessed using the MOCART (magnetic resonace observation of cartilage repair tissue) score, the WORMS (Whole-Organ Magnetic Resonance Imaging Score), and the CROAKS (Cartilage Repair Osteoarthritis Knee Score). Clinical symptoms were assessed using the Tegner activity and Lysholm knee scores. Statistical analyses were performed by using multiple linear regression analysis. Results: Total WORMS (P = .02) and MOCART (P = .001) scores significantly improved over 24 months after MACI. Clinical symptoms were significantly associated with the presence of bone marrow edema pattern abnormalities 24 months after surgery (P = .035). Overall there was a good to excellent radiological outcome found after 24 months (MOCART score, 88.8 ± 10.1). Cartilage repair T2 values significantly decreased between 12 and 24 months after MACI (P = .009). Lower global T2 values after 3 months were significantly associated with better MOCART scores after 24 months (P = .04). Moreover, trabecular bone parameters after 3 months were significantly associated with the total WORMS after 24 months (apparent bone fraction, P = .048; apparent trabecular number, P = .013; apparent trabecular separation, P = .013). Conclusion: After MACI with ABG, early postoperative quantitative assessment of biochemical composition of cartilage and microstructure of subchondral bone may predict the outcome after 24 months. The perioperative global joint cartilage matrix quality is essential for proper proliferation of the repair tissue, reflected by MOCART scores. The subchondral bone quality of the ABG site is essential for proper maturation of the cartilage repair tissue, reflected by cartilage T2 values.

PBI21 TREATMENT COSTS OF MATRIX-ASSOCIATED AUTOLOGOUS CHONDROCYTES IMPLANTATION COMPARED TO MICROFRACTURE — RESULTS OF A MATCHED-PAIR CLAIMS DATA ANALYSIS ON TREATMENT OF CARTILAGE KNEE DEFECTS IN GERMANY

Articular cartilage damage might lead to osteoarthritis, which represents a huge socioeconomic burden. Cartilage damage in the knee is commonly surgically treated with microfracture (MFX) or matrix-associated chondrocyte implantation (M-ACI). The objective of this study was to quantify costs associated with these treatments from the view of the statutory health insurance in Germany. This comparative study was based on an anonymized representative claims dataset of 4 million patients in Germany. Patients undergoing treatment with M-ACI or MFX for cartilage damages in the knee between 01.01.2012 and 31.12.2013 were followed-up for five years. Groups were adjusted via propensity score matching before initial treatment. The matched cohorts were compared regarding their outpatient, inpatient, pharmaceutical and other costs. In total 127 patients per group were analysed. In the year of the initial surgery, costs were 14,804 € and 5,459 € in the M-ACI respectively MFX group. In years two to three after the initial surgery, treatment costs were comparable between patients treated with M-ACI and MFX (2,898 and 2,115 € resp. 2,843 and 1,967 €), with slightly higher treatment costs of M-ACI treated patients. In years four and five after surgery, patients treated with M-ACI became less expensive (2,155 € and 1,478 resp. 2,233 € and 2,062 €). Costs in years with the need of re-surgeries were on average 3,732 € for M-ACI respectively 3,765 € for MFX treated patients. Thus, additional costs in years with re-surgeries were 1,672 € (M-ACI) resp. 1,915 € (MFX). We showed with a large, population representative claims data base and matched cohorts that follow-up costs of patients treated with M-ACI and MFX begin to converge over time. We found that additional costs for M-ACI are lower than previously reported and M-ACI might therefore be a cost-effective treatment in a shorter follow-up period than previously thought.

New Perspectives of Osteochondral Lesion of the Talus

Osteochondral lesions of the talus(OLT) are the most common articular cartilage defects in the ankle and may cause disability as a result of chronic pain and limited weight-bearing capacity. Numerous treatment strategies for symptomatic OLT have advanced significantly over the past decades.OLT are often managed conservatively for an initial stage before the surgical treatment. However, the conservative management determined solely on symptomatology, and not on the physiological healing. A systematic review for the treatment of OLT demonstrated a 45% success rate of non-operative management. Surgical treatment of OLT is reserved for symptomatic focal lesions that fail to respond to conservative treatments. There are three major operative strategies for OLT, reparative, replacement and regenerative manners.For the reparative modality, arthroscopic bone marrow stimulation(BMS) is widely regarded as the first-line treatment for OLT, as it is a technically undemanding, cost-effective, and minimally invasive procedure with low rates of complication and postoperative pain. Small lesion (<15 mm in diameter or <150mm2 in size) is the ideal candidate for BMS supported by several literatures. And a study reported the long-term follow-up study to date at 8-20 years after BMS in which 78% of patients had an excellent or good functional outcome score.As a replacement strategy, autologous osteochondral transplantation(AOT) is often indicated for symptomatic large, cystic lesions, including those that have failed previous reparative procedures, such as BMS. Osteochondral autograft transfer carries the inherent advantage over osteochondral allograft of being from the host with fresh viable cartilage, most commonly harvested from the ipsilateral knee. Clinical studies have found favorable results with osteochondral autograft techniques, including a recent systematic review of clinical outcomes at mid-term follow-up demonstrating excellent or good outcomes in 87% of patients.In recent years, Scaffold-based regenerative techniques are getting more attention. Matrix-associated chondrocyte implantation(MACI) is a 2-step procedure in which culture-expanded autologous chondrocytes are seeded on a scaffold, which is then secured in the OLT. More recently, 1-step procedures have been developed in which scaffolds and/or orthobiologics, including bone marrow aspirate concentrate(BMAC) and platelet-rich plasma(PRP), and hyaluronic acid(HA) have been used to augment microfracture with the intention of overcoming the 2-step procedures while concurrently promoting chondrogenic differentiation of endogenous stem cells. Matrix-augmented BMS is one such technique that has been reported with good results in case series.In the future, an advanced strategy for tissue engineering with gene therapy may influence the quality of integration and longevity in treatment of OLT.

Matrix-Associated Chondrocyte Implantation Is Associated With Fewer Reoperations Than Microfracture: Results of a Population-Representative, Matched-Pair Claims Data Analysis for Cartilage Defects of the Knee.

Background:Symptomatic cartilage defects of the knee are commonly surgically treated by microfracture (MFX) or matrix-associated chondrocyte implantation (M-ACI). Several randomized controlled trials have compared MFX and M-ACI, showing a tendency to lower reoperation rates for M-ACI, but results vary widely between studies.Purpose:To compare reoperation rates after MFX and M-ACI in cartilage defects of the knee outside clinical trials in a representative sample of the population.Study Design:Cohort study; Level of evidence, 3.Methods:This study was based on anonymized, population-representative claims data of 4 million insured persons in Germany. Patients who underwent MFX or M-ACI for cartilage defects of the knee with a follow-up of 2 years were compared. The primary endpoint was the need for a reoperation, defined as a claim for a second surgical procedure from the same patient at the knee joint (27 procedure codes), meniscus and cartilage (35 procedure codes), or patella (102 procedure codes) or the need for knee replacement (11 procedure codes). Group comparisons were performed using log-rank tests, with a 2-sided P value of <.05 to indicate significance. For adjusted analysis, propensity score matching was applied. Age, sex, comedications, and comorbidities were used as matching parameters.Results:A total of 6425 patients fulfilled the inclusion criteria: 6273 treated with MFX and 152 treated with M-ACI (mean age, 53 and 36 years, respectively). In the 2 years after treatment, 1271 patients in the MFX group needed a reoperation compared with 19 in the M-ACI group (20.3% vs 12.5%, respectively; P = .0199). For adjusted analysis after propensity score matching, 127 patients per group were analyzed. Their mean age was 37 years. At the end of the second follow-up year, 28 and 16 patients needed reoperations in the MFX and M-ACI groups, respectively (22.0% vs 12.6%, respectively; P = .0498).Conclusion:This study used a representative sample of the population and a broad definition of a reoperation, thus expanding evidence from clinical trials. We found a significant advantage of M-ACI in reoperation rates 2 years after treatment. After adjusting for age, sex, comedications, and comorbidities, M-ACI still showed significantly lower reoperation rates after 2 years.

Reconstruction of osteochondral defects by combined bone grafting and a bilayer collagen membrane as a sandwich technique

Treatment of osteochondral lesions of the knee remains a major challenge in orthopedic surgery. Recently established procedures like autologous chondrocyte implantation or matrix-associated chondrocyte implantation yield good results, but include the disadvantage of two-step procedures. The purpose of this study was to evaluate the clinical and magnetic resonance imaging outcome of repairs of osteochondral defects of the knee by a combined procedure of bone grafting and covering with a bilayer collagen membrane in a sandwich technique. Seven male patients with a mean age of 42 (range 30-55) years and symptomatic focal osteochondral lesions of the knee grade IV according to the International Cartilage Repair Society classification were included. The mean diameter of defects was 28.6 (range 15-40) mm. Results were evaluated at a minimum of 24 months after surgery by International Knee Documentation Committee score, Lysholm-score, visual analogue scale, and magnetic resonance imaging with specific cartilage sequences, evaluating the ICRS score and the Magnetic Observation of Cartilage Repair Tissue (MOCART) score. All patients judged the operation as successful. Among the patients available for the long-term follow-up, mean visual analogue scale value was 1.3 (range 0-3) out of 10 points. Mean International Knee Documentation Committee score was 80.8 (range 63.2-88.5) out of 100 points. Mean Lysholm score was 85 (range 55-95) out of 100 points. None of the patients had to be reoperated until today. Evaluation of magnetic resonance imaging using the MOCART score revealed a good correlation to the clinical outcome. This is the first study reporting results after reconstruction of osteochondral defects of the knee joint by bone grafting and a bilayer collagen membrane. This new method offers the advantage of a one-step-procedure and yields both good clinical and magnetic resonance findings. We conclude that this procedure can be a valuable tool to improve joint function after osteochondral defects, trauma, and in joints with local arthritic lesions.

New perspectives in the treatment of cartilage damage. Poly(ethylene glycol) diacrylate (PEGDA) scaffold. A review.

This review was conducted as a complementary study to our review "Current concepts in the treatment of cartilage damage. A review", in this same Journal, on promising new strategies in the treatment of cartilage defects. The established treatments such as osteochondral implants, bone marrow stimulation techniques and chondrogeneic cell implantations, besides advantages, have drawbacks that have led to seek new strategies such as scaffold materials. Matrix-associated chondrocyte implantation, hyaluronan-based scaffolds, tissue-engineered collagen matrices seeded with autologous chondrocytes and encapsulation of autologous chondrocytes in poly(ethylene glycol) diacrylate (PEGDA) seem to be less invasive and have a good performance. In this review we describe benefits and disadvantages of the new procedures of cartilage regeneration by scaffolding materials such as PEGDA.

Management of Articular Cartilage Defects of the Knee

Articular cartilage injuries of the knee present a difficult clinical dilemma and their treatment is controversial. Hyaline articular cartilage is an avascular, low-friction, and wear-resistant weightbearing surface that has limited capacity for self-repair. The optimal treatment for cartilage lesions has yet to be established. Various treatment methods are employed to reestablish a stable cartilage surface, including microfracture, autologous and allograft osteochondral transplantation, autologous chondrocyte implantation, matrix-associated chondrocyte implantation, and scaffold-assisted methods. Treatment algorithms help to guide physicians' decision making in the care of these injuries. In this article, results from outcomes studies as well as prospective randomized clinical trials comparing treatment methods are reviewed, and current practice guidelines are summarized.

Paper # 168: Matrix-Associated Chondrocyte Implantation Combined with Bone Graft for the Repair of Osteochondral Defects in the Knee: Clinical Results and MRI Follow-ups

Osteochondral defects in the knee are primarily based on pathologic changes of the subchondral bone, which affect the chondral surface. Repair depends on reconstruction of cartilage and bone. The Matrix-associated Chondrocyte Implantation (MACI) is a third generation cartilage regeneration technique where chondrocytes are seeded onto a collagen I/III membrane. The MACI technique was combined with an autologous bone graft (BG) in a two-step sandwich procedure (MACI-BG). Goal of our prospective observational study was to evaluate the outcomes after two years.

Arthroscopic Treatment of Osteochondral Lesions of the Ankle With Matrix-Associated Chondrocyte Implantation

Background: Conventional autologous chondrocyte transplantation in the ankle often requires tibial or fibular osteotomies with potential morbidity for the patient. Advances in biotechnology and surgical techniques have resulted in the development of matrix-associated chondrocyte implantation (MACI). As the chondrocyte-loaded scaffold can be applied arthroscopically, this procedure is especially useful for the treatment of osteochondral defects in the ankle. Hypothesis: Arthroscopic MACI is a safe procedure in the ankle with good clinical and magnetic resonance imaging results. Study Design: Case series; Level of evidence, 4. Methods: The authors reviewed all patients (n = 18) who had arthroscopic MACI for osteochondral lesions of the ankle (n = 19) between February 2006 and May 2008 clinically and with magnetic resonance imaging. The pain and disability module of the Foot Function Index (FFI), the American Orthopaedic Foot & Ankle Society (AOFAS) clinical rating system, the Core Scale of the Foot and Ankle Module of the American Academy of Orthopaedic Surgeons (AAOS) Lower Limb Outcomes Assessment Instruments, and the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score were used. The clinical results up to 3 years after MACI (mean follow-up, 24.5 months) were compared with preoperative data for 14 cases and the magnetic resonance imaging data for all 19. Results: A significant improvement (50.3% ± 13.2%) in all clinical scores was noted (FFI pain before MACI: 5.5 ± 2.0, after MACI: 2.8 ± 2.2; FFI disability before MACI: 5.0 ± 2.3, after MACI: 2.6 ± 2.2; AOFAS before MACI: 58.6 ± 16.1, after MACI: 80.4 ± 14.1; AAOS standardized mean before MACI: 59.9 ± 16.0, after MACI: 83.5 ± 13.2; AAOS normative score before MACI: 23.0 ± 13.0, after MACI: 42.2 ± 10.7). According to the AOFAS Hindfoot score, 64% were rated as excellent and good, whereas 36% were rated fair and poor. The results correlated with the age of the patient and the duration of symptoms, but not with the size of the lesion. Sixteen patients (89%) reported regular sports activities before the onset of symptoms; 13 of them (81%) returned to sports after the MACI, 56% (n = 9) to the same level. The mean MOCART score was 62.4 ± 15.8 points. In general, there was no relation between MOCART score and clinical outcome, although the filling of the defect showed some correlation with the AAOS score. Conclusion: Arthroscopic MACI is a safe procedure for the treatment of osteochondral lesions in the ankle with overall good clinical and magnetic resonance imaging results.

In-vitro-Studie zum Einfluss von Fibrin in Knorpelkonstrukten auf der Basis von PGA-Vliesstoffen

The matrix component in autologous chondrocyte implantation plays an important role. In this study the influence of an additional fibrin component in cartilage constructs based on polyglycolide polymers (PGA) was investigated. Human chondrocytes of femoral heads were isolated and cultured using a serum-free technique. The cells were seeded on PGA-91 scaffolds with and without an additional fibrin component; the constructs were cultured for 2 weeks in vitro. Besides cell viability, DNA content, pH, aggrecan production, mRNA expression of aggrecan, and collagen types I and II were determined by real-time PCR. Furthermore, cartilage grafts were histologically analyzed. All constructs contained viable, metabolically active cells in the investigated time period. There was no cell proliferation within the graft, and the DNA content was decreased over time. The pH level constantly remained within a physiologic range. The Alcian blue staining of the constructs showed the homogeneous cell distribution and a cell-associated proteoglycan production. Aggrecan concentration in the supernatants of fibrin-containing constructs was significantly lower compared to fibrin-free grafts (-24%), a result that correlated with diminished aggrecan mRNA expression (-80%). mRNA expression of collagen type II increased in the fibrin-free constructs over time and was 57% higher than in the fibrin-containing grafts. The immunohistochemical detection of collagen type II was possible in all constructs. Cartilage constructs based on carbohydrate matrices are suitable for matrix-associated chondrocyte implantation. The results of this study suggest a partially inhibitory effect of an additional fibrin component in PGA constructs for chondrogenic differentiation.