Collagen-covered versus matrix-induced autologous chondrocyte implantation for osteochondral defects of the knee: a comparison of tourniquet times

We have compared tourniquet times of two techniques of autologous chondrocyte implantation (ACI). Seventy-three patients underwent the collagen covered ACI technique (ACI-C) and 63 patients underwent the matrix-induced autologous chondrocyte implantation technique (MACI) for symptomatic osteochondral defects of the knee, at our centre, as part of a prospective trial. The mean tourniquet time in the ACI-C group was 80.7 min (range 47–126), and 61.5 min (range 27–100) in the MACI group, P=0.003. Tourniquet times greater than 90 min were required in 22 (31%) ACI procedures and 1 (2%) MACI procedure. The reduced implantation time for the MACI procedure is a clinically significant advantage, and allows cartilage resurfacing to be performed in combination with other techniques within safe tourniquet times.     

The role of autologous chondrocyte implantation in the treatment of symptomatic chondromalacia patellae

Purpose

Chondromalacia patella is a distinct clinical entity of abnormal softening of the articular cartilage of the patella, which results in chronic retropatellar pain. Its aetiology is still unclear but the process is thought to be a due to trauma to superficial chondrocytes resulting in a proteolytic enzymic breakdown of the matrix. Our aim was to assess the effectiveness of autologous chondrocyte implantation on patients with a proven symptomatic retropatellar lesion who had at least one failed conventional marrow-stimulating therapy.

Methods

We performed chondrocyte implantation on 48 patients: 25 received autologous chondrocyte implantation with a type I/III membrane (ACI-C) method (Geistlich Biomaterials, Wolhusen, Switzerland), and 23 received the Matrix-assisted Chondrocyte Implantation (MACI) technique (Genzyme, Kastrup, Denmark).

Results

Over a mean follow-up period of 40.3 months, there was a statistically significant improvement in subjective pain scoring using the visual analogue scale (VAS) and objective functional scores using the Modified Cincinnati Rating System (MCS) in both groups.

Conclusions

Chondromalacia patellae lesions responded well to chondrocyte implantation. Better results occurred with MACI than with ACI-C. Excellent and good results were achieved in 40% of ACI-C patients and 57% of MACI patients, but success of chondrocyte implantation was greater with medial/odd-facet lesions. Given that the MACI procedure is technically easier and less time consuming, we consider it to be useful for treating patients with symptomatic chondral defects secondary to chondromalacia patellae.     

Autologous chondrocyte implantation at the knee using a bilayer collagen membrane with bone graft. A preliminary report

Autologous chondrocyte implantation (ACI) is a technique used for the treatment of symptomatic osteochondral defects of the knee. A variation of the original periosteum membrane technique is the matrix-induced autologous chondrocyte implantation (MACI) technique. The MACI membrane consists of a porcine type-I/III collagen bilayer seeded with chondrocytes. Osteochondral defects deeper than 8 to 10 mm usually require bone grafting either before or at the time of transplantation of cartilage. We have used a variation of Peterson's ACI-periosteum sandwich technique using two MACI membranes with bone graft which avoids periosteal harvesting. The procedure is suture-free and requires less operating time and surgical exposure. We performed this MACI-sandwich technique on eight patients, five of whom were assessed at six months and one year post-operatively using the modified Cincinnati knee, the Stanmore functional rating and the visual analogue pain scores. All patients improved within six months with further improvement at one year. The clinical outcome was good or excellent in four after six months and one year. No significant graft-associated complications were observed. Our early results of the MACI-sandwich technique are encouraging although larger medium-term studies are required before there is widespread adoption of the technique.     

Collagen-covered autologous chondrocyte implantation for osteochondritis dissecans of the knee: two- to seven-year results

We prospectively studied the clinical, arthroscopic and histological results of collagen-covered autologous chondrocyte implantation (ACI-C) in patients with symptomatic osteochondritis dissecans of the knee. The study included 37 patients who were evaluated at a mean follow-up of 4.08 years.Clinical results showed a mean improvement in the modified Cincinnati score from 46.1 to 68.4. Excellent and good clinical results were seen in 82.1% of those with juvenile-onset osteochondritis dissecans but in only 44.4% of those with adult-onset disease.Arthroscopy at one year revealed International Cartilage Repair Society grades of 1 or 2 in 21 of 24 patients (87.5%). Of 23 biopsies, 11 (47.8%) showed either a hyaline-like or a mixture of hyaline-like and fibrocartilage, 12 (52.2%) showed fibrocartilage.The age at the time of ACI-C determined the clinical outcome for juvenile-onset disease (p = 0.05), whereas the size of the defect was the major determinant of outcome in adult-onset disease (p = 0.01).     

Arthroscopic autologous chondrocyte implantation for the treatment of a chondral defect in the tibial plateau of the knee

The matrix-induced autologous chondrocyte implantation (MACI; Verigen, Leverküsen, Germany) is a tissue engineering technique for the treatment of deep chondral lesions. Cultured chondrocytes are seeded on a collagen membrane that can be implanted into the defect using exclusively fibrin glue. These features imply some surgical advantages with respect to the traditional ACI technique, such as the possibility of performing the procedure in articular sites, in which putting stitches for the periosteal patch is impossible. We report on the arthroscopic MACI technique for the treatment of a chondral defect of the knee. A 25-year-old man suffered persistent pain at the left knee after a violent direct trauma. Magnetic resonance imaging (MRI) and arthroscopic examination at the time of cartilage biopsy revealed a 2-cm² chondral lesion in the posterior portion of the lateral tibial plateau. The implantation procedure was performed through traditional arthroscopic portals, and the seeded membrane was fixed with fibrin glue, excluding water flow temporarily. Implant stability was verified intraoperatively, and filling of the defect was shown 12 months after surgery by MRI, which showed a hyaline-like cartilage signal. In this specific case, the arthroscopic approach allowed to achieve an optimal view of the lesion, without sacrificing any tendinous or ligamentous structure of the knee.     

Autologous chondrocyte implantation for focal cartilage defects in athletes: histology and second-look arthroscopy

Abstract Previous studies of autologous chondrocyte implantation reported good results in the general population. This study was undertaken to evaluate outcomes in high-level competitive athletes. We tested the hypothesis that cartilage resurfacing with autologous chondrocytes is an effective treatment for symptomatic chondral lesions in high-level athletes. We prospectively evaluated 5 male athletes with large (3-10 cm²) symptomatic grade III-IV chondral injuries of the knee.Clinical evaluations were performed at baseline and 3, 6, 12, and 24 months after chondrocyte implantation. All patients underwent secondlook arthroscopy at one year and were evaluated macroscopically using a standardized scoring system. Three patients consented to biopsy and histological analysis of repair tissue at one or more years after implantation. Overall, scores of patients subjective ratings improved from a mean of 2.4 at baseline (poor: significant limitations affecting activities of daily living) to 9.4 (very good: only a few limitations with sports) at 12 months on a modified Cincinnati scale. All patients returned to pre-injury level of sports participation. Macroscopic evaluation showed tissue similar in appearance and consistency to normal cartilage. Histological results in 3 of 5 patients showed organization and type II collagen staining similar to normal cartilage. Autologous chondrocyte implantation successfully returned all patients to pre-injury levels of sports participation.Macroscopic and histologic evaluations showed repair tissue with the characteristics of normal cartilage.     

Early results of autologous chondrocyte implantation in the talus

Autologous chondrocyte implantation (ACI) has been used most commonly as a treatment for cartilage defects in the knee and there are few studies of its use in other joints. We describe ten patients with an osteochondral lesion of the talus who underwent ACI using cartilage taken from the knee and were prospectively reviewed with a mean follow-up of 23 months. In nine patients the satisfaction score was 'pleased' or 'extremely pleased', which was sustained at four years. The mean Mazur ankle score increased by 23 points at a mean follow-up of 23 months. The Lysholm knee score returned to the pre-operative level at one year in three patients, with the remaining seven showing a reduction of 15% at 12 months, suggesting donor-site morbidity. Nine patients underwent arthroscopic examination at one year and all were shown to have filled defects and stable cartilage. Biopsies taken from graft sites showed mostly fibrocartilage with some hyaline cartilage. The short-term results of ACI for osteochondral lesions of the talus are good despite some morbidity at the donor site.     

Autologous chondrocyte implantation in a novel alginate-agarose hydrogel: outcome at two years

Autologous chondrocyte implantation is an established method of treatment for symptomatic articular defects of cartilage. CARTIPATCH is a monolayer-expanded cartilage cell product which is combined with a novel hydrogel to improve cell phenotypic stability and ease of surgical handling. Our aim in this prospective, multicentre study on 17 patients was to investigate the clinical, radiological, arthroscopic and histological outcome at a minimum follow-up of two years after the implantation of autologous chondrocytes embedded in a three-dimensional alginate-agarose hydrogel for the treatment of chondral and osteochondral defects. Clinically, all the patients improved significantly. Patients with lesions larger than 3 cm(2) improved significantly more than those with smaller lesions. There was no correlation between the clinical outcome and the body mass index, age, duration of symptoms and location of the defects. The mean arthroscopic International Cartilage Repair Society score was 10 (5 to 12) of a maximum of 12. Predominantly hyaline cartilage was seen in eight of the 13 patients (62%) who had follow-up biopsies. Our findings suggest that autologous chondrocyte implantation in combination with a novel hydrogel results in a significant clinical improvement at follow-up at two years, more so for larger and deeper lesions. The surgical procedure is uncomplicated, and predominantly hyaline cartilage-like repair tissue was observed in eight patients.     

The use of debrided human articular cartilage for autologous chondrocyte implantation: maintenance of chondrocyte differentiation and proliferation in type I collagen gels.

Autologous chondrocyte implantation (ACI) is the most promising surgical treatment for large full thickness knee joint articular cartilage (AC) defects where cells from healthy non-weight bearing area AC are multiplied in vitro and implanted into such defects. In the routine surgical procedure for symptomatic knee full thickness AC defects, damaged AC surrounding the edge and the base of such defects is usually debrided and discarded. The purpose of this study was to examine if chondrocytes from this 'debrided' AC can proliferate, synthesize a cartilage specific matrix and thus can be used for ACI. METHODS: Biopsies were retrieved from 12 patients (debrided articular cartilage: DAC, aged 35-61) and from two autopsies (normal articular cartilage: NAC, aged 21 and 25). Chondrocytes were isolated, seeded at low density in type I collagen gels and as monolayer cultures for 4 weeks without passage. RESULTS: After 4 weeks cultures in type I collagen gels, cell proliferation from DAC (18.34 +/- 1.95 fold) was similar to cells from NAC (11.24 +/- 1.02 fold). Syntheses of proteoglycan and collagen in DAC were also similar to NAC. Newly synthesized matrices in gel cultures consisted predominantly of type II collagen as shown by immuno-labelling and SDS-PAGE followed by fluorography. Chondrocytes from 'debrided human AC' cultured at low density in type I collagen gels may be used for the ACI procedure as they provide sufficient viable cell numbers for ACI and maintain their chondrocyte phenotype as they synthesize a cartilage-like matrix.     

Treatment of full-thickness chondral defects in the knee with autologous chondrocyte implantation

Autologous chondrocyte implantation (ACI) has now been performed for over a decade in the United States. ACI has been demonstrated as a reproducible treatment option for large, full-thickness, symptomatic chondral injuries of the knee. As clinical experience has expanded and indications broadened to more complex cartilage defects, it has become evident that aggressive treatment of coexisting knee pathology is essential for optimal results. This includes management of malalignment, ligamentous, and/or meniscal deficiency, and subchondral bone loss to make the intra-articular environment as ideal as possible for successful cartilage restoration. Additionally, refinements in the rehabilitation necessary for biologic cartilage repair have been made, based on better understanding of the maturation process of the repair cartilage, allowing for earlier initiation of knee range of motion, strengthening exercises, and weight bearing. These changes have enhanced the recovery for the patient and decreased the risk of motion deficits. This article will discuss patient selection for ACI, review ACI surgical technique, including management of coexisting knee pathology, present postoperative ACI rehabilitation guidelines, and summarize clinical outcomes after ACI.     

Treatment of full-thickness chondral defects with autologous chondrocyte implantation

Autologous chondrocyte implantation (ACI) is a reproducible treatment option for large full-thickness symptomatic chondral injuries with appropriate knowledge of technique and patient selection. It provides a cellular repair that offers a high percentage of good to excellent clinical results over a long follow-up period. It is applicable over a wide range of chondral injuries from simple to more complex lesions. It is essential that the intra-articular environment be as close to normal as possible for successful cartilage repair. Coexisting knee pathology must be aggressively treated. ACI does have a prolonged postoperative rehabilitation course necessitated by the biologic nature of the repair, and patients must be able to comply with the rehabilitation and temporary restrictions required for a successful outcome.     

Histological evaluation of chondral defects after autologous chondrocyte implantation of the knee

We have performed a prospective, single-surgeon study analysing the histological results of autologous chondrocyte implantation. Fourteen patients underwent autologous chondrocyte implantation of the knee and were evaluated at one year by clinical assessment and arthroscopy. Standard staining was used to examine the sections. In addition, in situ hybridisation was used to establish type-IIa and type-IIb collagen mRNA expression and immunolocalisation techniques demonstrated the positions of type-II and type-X collagen. Eight patients regenerated hyaline cartilage and also contained type-X collagen in the deepest layers and type-II collagen in the deep layers. Three demonstrated fibrocartilage and had type-I collagen in the deep layers. In situ hybridisation revealed that all 14 samples had the potential to express both type-IIa and type-IIb collagen. We have shown that one year after the initial implantation chondrocytes are capable of producing type-II collagen and that they continue to proliferate and mature.     

Immature porcine knee cartilage lesions show good healing with or without autologous chondrocyte transplantation

OBJECTIVE: The purpose of this study was to find out how deep chondral lesions heal in growing animals spontaneously and after autologous chondrocyte transplantation. METHODS: A 6mm deep chondral lesion was created in the knee joints of 57 immature pigs and repaired with autologous chondrocyte transplantation covered with periosteum or muscle fascia, with periosteum only, or left untreated. After 3 and 12 months, the repair tissue was evaluated with International Cartilage Repair Society (ICRS) macroscopic grading, modified O'Driscoll histological scoring, and staining for collagen type II and hyaluronan, and with toluidine blue and safranin-O staining for glycosaminoglycans. The repair tissue structure was also examined with quantitative polarized light microscopy and indentation analysis of the cartilage stiffness. RESULTS: The ICRS grading indicated nearly normal repair tissue in 65% (10/17) after the autologous chondrocyte transplantation and 86% (7/8) after no repair at 3 months. At 1 year, the repair tissue was nearly normal in all cases in the spontaneous repair group and in 38% (3/8) in the chondrocyte transplantation group. In most cases, the cartilage repair tissue stained intensely for glycosaminoglycans and collagen type II indicating repair tissue with true constituents of articular cartilage. There was a statistical difference in the total histological scores at 3 months (P=0.028) with the best repair in the spontaneous repair group. A marked subchondral bone reaction, staining with toluidine blue and collagen type II, was seen in 65% of all animals. CONCLUSIONS: The spontaneous repair ability of full thickness cartilage defects of immature pigs is significant and periosteum or autologous chondrocytes do not bring any additional benefits to the repair.     

Improvement in bone homeostasis following autologous chondrocyte implantation of the knee

This retrospective review and clinical follow-up demonstrates the effectiveness of autologous chondrocyte implantation of the knee. From September 1995 to June 2001, 24 patients with average follow-up of 26.5 months were evaluated. The mean Lysholm score improved from 43.58 before surgery to 71.42 at most recent follow-up, the modified Cincinnati knee score for overall clinician evaluation improved from 2.96 to 6.92, and the mean modified Cincinnati knee score for overall patient evaluation improved from 3.21 to 6.13 at P <.05. Seventy-nine percent of patients responded that they would have the same knee surgery again and 83% rated the results of their knee surgery as good to excellent. Limited radionuclide bone scans with single photon emission computed tomography were completed in 11 of the patients to assess the physiology and homeostasis of subchondral bone adjacent to treated articular cartilage defects. A trend was identified suggesting improvement in subchondral bone scores at a mean of 29.6-months follow-up compared to preoperative bone scan assessment. There also was a trend towards greatest improvement correlating with the patients with the best clinical scores. The results of this study suggest that autologous chondrocyte implantation of the knee can be successful in improving pain and function in patients with articular cartilage defects.     

Who is the ideal candidate for autologous chondrocyte implantation?

We investigated the prognostic indicators for collagen-covered autologous chondrocyte implantation (ACI-C) performed for symptomatic osteochondral defects of the knee.We analysed prospectively 199 patients for up to four years after surgery using the modified Cincinnati score. Arthroscopic assessment and biopsy of the neocartilage was also performed whenever possible. The favourable factors for ACI-C include younger patients with higher pre-operative modified Cincinnati scores, a less than two-year history of symptoms, a single defect, a defect on the trochlea or lateral femoral condyle and patients with fewer than two previous procedures on the index knee. Revision ACI-C in patients with previous ACI and mosaicplasties which had failed produced significantly inferior clinical results. Gender (p = 0.20) and the size of the defect (p = 0.97) did not significantly influence the outcome.     

Matrix‐induced autologous chondrocyte implantation in sheep: objective assessments including confocal arthroscopy

The assessment of cartilage repair has largely been limited to macroscopic observation, magnetic resonance imaging (MRI), or destructive biopsy. The aims of this study were to establish an ovine model of articular cartilage injury repair and to examine the efficacy of nondestructive techniques for assessing cartilage regeneration by matrix‐induced autologous chondrocyte implantation (MACI). The development of nondestructive assessment techniques facilitates the monitoring of repair treatments in both experimental animal models and human clinical subjects. Defects (Ø 6 mm) were created on the trochlea and medial femoral condyle of 21 sheep randomized into untreated controls or one of two treatment arms: MACI or collagen‐only membrane. Each group was divided into 8‐, 10‐, and 12‐week time points. Repair outcomes were examined using laser scanning confocal arthroscopy (LSCA), MRI, histology, macroscopic ICRS grading, and biomechanical compression analysis. Interobserver analysis of the randomized blinded scoring of LSCA images validated our scoring protocol. Pearson correlation analysis demonstrated the correlation between LSCA, MRI, and ICRS grading. Testing of overall treatment effect independent of time point revealed significant differences between MACI and control groups for all sites and assessment modalities (Asym Sig < 0.05), except condyle histology. Biomechanical analysis suggests that while MACI tissue may resemble native tissue histologically in the early stages of remodeling, the biomechanical properties remain inferior at least in the short term. This study demonstrates the potential of a multisite sheep model of articular cartilage defect repair and its assessment via nondestructive methods. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:292–303, 2008     

A prospective,randomised comparison of autologous chondrocyte implantation versus mosaicplasty for osteochondral defects in the knee

Autologous chondrocyte implantation (ACI) and mosaicplasty are both claimed to be successful for the repair of defects of the articular cartilage of the knee but there has been no comparative study of the two methods. A total of 100 patients with a mean age of 31.3 years (16 to 49) and with a symptomatic lesion of the articular cartilage in the knee which was suitable for cartilage repair was randomised to undergo either ACI or mosaicplasty; 58 patients had ACI and 42 mosaicplasty. Most lesions were post-traumatic and the mean size of the defect was 4.66 cm2. The mean duration of symptoms was 7.2 years and the mean number of previous operations, excluding arthroscopy, was 1.5. The mean follow-up was 19 months (12 to 26). Functional assessment using the modified Cincinatti and Stanmore scores and objective clinical assessment showed that 88% had excellent or good results after ACI compared with 69% after mosaicplasty. Arthroscopy at one year demonstrated excellent or good repairs in 82% after ACI and in 34% after mosaicplasty. All five patellar mosaicplasties failed. Our prospective, randomised, clinical trial has shown significant superiority of ACI over mosaicplasty for the repair of articular defects in the knee. The results for ACI are comparable with those in other studies, but those for mosaicplasty suggest that its continued use is of dubious value.     

Autologous implantation of chondrocytes on a solid collagen scaffold: clinical and histological outcomes after two years of follow-up

Abstract From our overall experience in 56 patients, we here report the treatment with matrix-induced autologous chondrocyte implantation (MACI) of 35 patients suffering from knee cartilage defects measuring about 4 cm², and followed for a minimum of 6 months. A total of 36 knees were treated (1 patient on both knees) and clinically observed for 22 months (in some cases for over 39 months), in accordance with a standardised protocol. Subjective parameters (pain, well-being, functional state, symptoms during specific activity) and objective outcomes (IKDC score and Lysholm and Tegner scores) were recorded. One or 2 years after implantation, some biopsies of the regenerated cartilage were histologically evaluated. The subjective parameters (VAS pain score, 2.80±1.49, p<0.0001; change vs. basal score, 2.72) promptly normalized after 1 month, as did the objective ones (IKDC score after 6 months, 1.53±0.59, p<0.0001; change vs. basal score, 1.78). Similar results were observed after the treatment of a femoropatellar kissing lesion. The three cartilage biopsies that were analysed from different patients showed a tissue positivity to immunohistochemical markers of hyaline cartilage. The conclusions of this preliminary analysis are that the clinical outcome and histological evaluation suggest that MACI is able to relieve pain and restore the functionality of the knee, and that the treatment appears capable of regenerating hyaline cartilage.     

Minimum ten-year results of a prospective randomised study of autologous chondrocyte implantation versus mosaicplasty for symptomatic articular cartilage lesions of the knee

Autologous chondrocyte implantation (ACI) and mosaicplasty are methods of treating symptomatic articular cartilage defects in the knee. This study represents the first long-term randomised comparison of the two techniques in 100 patients at a minimum follow-up of ten years. The mean age of the patients at the time of surgery was 31.3 years (16 to 49); the mean duration of symptoms pre-operatively was 7.2 years (9 months to 20 years). The lesions were large with the mean size for the ACI group being 440.9 mm(2) (100 to 1050) and the mosaicplasty group being 399.6 mm(2) (100 to 2000). Patients had a mean of 1.5 previous operations (0 to 4) to the articular cartilage defect. Patients were assessed using the modified Cincinnati knee score and the Stanmore-Bentley Functional Rating system. The number of patients whose repair had failed at ten years was ten of 58 (17%) in the ACI group and 23 of 42 (55%) in the mosaicplasty group (p < 0.001). The functional outcome of those patients with a surviving graft was significantly better in patients who underwent ACI compared with mosaicplasty (p = 0.02).     

Factors affecting the efficacy of bovine chondrocyte transplantation in vitro.

Current therapies for osteoarthritis have been primarily directed at symptom relief rather than disease modification or cure. Improved understanding of cartilage biology and metabolism has permitted exploration of disease-modifying treatments for OA. Chondrocyte transplantation is one approach to disease modification that has received increasing attention. To date, most chondrocyte transplantation has focused on surgical implantation into isolated chondral defects.Our hypothesis is that cultured chondrocytes will preferentially transplant to hyaline cartilage after intraarticular injection. The purpose of this study was to quantify chondrocyte adherence to cartilage in an in-vitro bovine explant model under differing culture conditions. The effect on chondrocyte transplantation of time, of alginate vs. monolayer culture techniques, and of differing origin of tissue explants within the knee joint were assessed. The effect on transplantation of physically modifying the explant surface was also assessed. In addition to quantification of transplantation adherence, the morphology of transplanted chondrocytes was assessed with confocal and electron microscopy.Maximal adherence occurred by 24 h post-transplantation. Baseline transplant densities exceeding 1 x 10(6) cells/cm(2)were observed on unmodified cartilage surfaces. No significant differences in binding density were noted between cartilage explants obtained from the patella, femoral condyles, tibial plateaus or the trochlear groove. In addition, no differences in chondrocyte adherence were noted in cells cultured in monolayer or alginate beads. Transplanted chondrocytes were noted to be spherical irrespective of the culture methods employed. Notably, chondrocytes demonstrated significantly improved adherence to cartilage surfaces after the superficial layer was removed as compared to normal intact cartilage surfaces (increase of 26%, P< 0. 01). This suggests that chondrocytes may preferentially adhere to cartilage surfaces where the superficial layer has been damaged, as is the case in isolated chondral lesions, or with diffuse cartilage degeneration.