Arthroscopic Autologous Chondrocyte Implantation Research Articles

Arthroscopic autologous chondrocyte implantation in the knee with an in situ crosslinking matrix: minimum 4-year clinical results of 15 cases and 1 histological evaluation.

To clinically evaluate an arthroscopic autologous chondrocyte implantation (ACI) technique with an in situ crosslinking matrix for the treatment of full thickness cartilage defects of the knee and to present histological results of a graft cartilage biopsy obtained after 1.5years. Fifteen cases of arthroscopic autologous chondrocyte implantation in the knee performed between November 2011 and October 2012 were included in the study. Medical charts and operational reports were screened and the patients were contacted after 0.8 ± 0.3years (0.4-1.3) and 4.3 ± 0.3years (4.0-4.8) to asses subjective IKDC and re-operation. The Tegner activity scale was collected at the second follow-up time point. Subjective IKDC response rates were assessed at both follow-up time points. The first and second follow-up was completed by all 15 patients (100%). The subjective IKDC scores showed a significant improvement (pre-operative 44.5 ± 15.9, first follow-up 71.1 ± 15.9, p < 0.001, second follow-up 72.6 ± 17.3, p < 0.001). The overall response rate was 66.7% (n = 10) at follow-up one and two. There were no significant differences in pre-injury (4, range 1-9) and follow-up two (4, range 2-7) Tegner activity scales (p = n.s.). Two patients required re-operation in the index knee, not related to the ACI procedure. No complication related to the ACI or the implantation technique occurred. The histological results showed excellent cartilage regeneration. Arthroscopic ACI using an in situ crosslinking matrix is a safe and reliable treatment option for full-thickness cartilage defects of the knee.

Arthroscopic autologous chondrocyte implantation in the hip for the treatment of full-thickness cartilage defects - A case series of 29 patients and review of the literature.

Purpose: Current literature indicates that the appropriate treatment of articular cartilage defects has significant influence on the postoperative outcome after hip arthroscopy. In the hip, arthroscopic treatment of cartilage defects is technically challenging, especially the autologous chondrocyte implantation/matrix-associated autologous chondrocyte implantation (ACI/MACI) procedures. The purpose of this prospective study was to introduce two injectable MACI products with self-adherent properties. Furthermore, we report short-term outcome and review the current literature. Methods: Full-thickness cartilage defects of 29 patients caused by the femoroacetabular impingement (FAI) were treated arthroscopically with an injectable MACI product in a two-step surgical procedure. The patient-related outcome was assessed with International Hip Outcome Tool (iHOT33), Euro-Quol group score (EQ-5D) and Non-Arthritic-Hip-Score (NAHS) at baseline, six weeks, six, 12 and 24 months. Results: Twenty-nine out of 46 patients (27 male/two female) with a mean age of 30.3 years (range 18–45 years) and an average defect size of 2.21 cm2 were available for follow-up after a mean of 19 months (range 6–24 months). All defects were located on the acetabulum International Cartilage Repair Society (ICRS) grade 3A–3D (nine 3A; eleven 3B; six 3C; three 3D). Twenty-six patients had associated labral pathology (23 repair 1–5 anchors; three partial trimming). Twenty-seven defects were caused by the FAI (20 CAM, six combined, one Pincer), two cases were of traumatic cause. An overall statistically significant improvement was observed for all assessment scores at an average follow-up of 19 months. Conclusion: In this study, we present short-term data of new arthroscopic injectable matrix-associated, autologous chondrocyte implants as a treatment option for full-thickness cartilage defects of the hip. All patient-administered assessment scores demonstrated an increase in activity level, quality of life and reduction of pain after a 19-month follow-up. Further randomized controlled trails (RCTs) with comparison of natural history, bone marrow stimulation techniques and MACI of the hip have to approve the results in long-term follow-up.

Cell Viability in Arthroscopic Versus Open Autologous Chondrocyte Implantation

Background: Autologous chondrocyte implantation (ACI) is an effective method of repair of articular cartilage defects. It is a 2-stage operation, with the second stage most commonly performed via mini-arthrotomy. Arthroscopic ACI is gaining popularity, as it is less invasive and may accelerate early rehabilitation. However, handling and manipulation of the implant have been shown to cause chondrocyte cell death. Purpose: To assess the number and viability of cells delivered via an open versus arthroscopic approach in ACI surgery. Study Design: Controlled laboratory study. Methods: Sixteen ACI surgeries were performed on young cadaveric knees by 2 experienced surgeons: 8 via mini-arthrotomy and 8 arthroscopically. Live and dead cells were stained and counted on implants after surgery. The cell number and viability were assessed using confocal laser scanning microscopy. Surgery was timed from knife to skin until the end of cycling the knee 10 times after implantation of the cell-membrane construct. Results: On receipt of cell membranes after transportation from the laboratory, ≥92% of the cells were viable. There were significantly more remaining cells (8.47E+07 arthroscopic vs 1.41E+08 open; P < .001) and 16 times more viable cells (3.62% arthroscopic vs 37.34% open; P < .001) on the implants when they were inserted via mini-open surgery compared with the arthroscopic technique. Open surgery was of a significantly shorter duration (6 vs 32 minutes; P < .001). Conclusion: In this study, there were significantly more viable cells on the implant when ACI was performed via mini-arthrotomy compared with an arthroscopic technique. Clinical Relevance: The viability of cells delivered for ACI via an arthroscopic approach was 16 times less than via an open approach. The mini-arthrotomy approach is recommended until long-term clinical comparative data are available.

Second-look assessment after all-arthroscopic autologous chondrocyte implantation with spheroides at the knee joint.

To report arthroscopic second look as well as clinical results after arthroscopic autologous chondrocyte implantation (ACI) for articular cartilage repair at the knee joint. A second-look assessment after arthroscopic ACI using spheroides was performed in 41 patients with 57 full-size articular cartilage defects of the knee. The median time from ACI to second-look arthroscopy was 10 (6-72) months. The ACI was assessed macroscopically and by probing according to the International Cartilage Repair Score (ICRS)-Cartilage Repair Assessment (CRA) to get information on the amount and quality of regeneration. Clinical follow-up with subjective outcome scores was performed an average of 34.5±19.2months after ACI. Twenty-seven (65.8%) of ACI's were combined with additional procedures. The ICRS-CRA was rated "normal" or "nearly normal" in 52 of 57 (91.3%) and "abnormal" in 5 (8.8%) of all cartilage defects. At follow-up, evaluation of KOOS was an average of 81.0±12.9 for pain, 76.8±16.6 for symptoms, 85.1±14.9 for activities of daily living, 55.3±27.7 for sport and recreation and 50.6±23.8 for quality of live. IKDC was 63.0±18.8, Lysholm score was 79.0±18.0, and Tegner score was 4 (1-6). Subjective assessment according to the VAS scale was an average of 7.4±2.1 for overall satisfaction and 6.7±2.5 satisfaction for the operated knee. Seven patients (22.6%) showed low subjective outcome scores at last follow-up-of these, 2 patients showed a CRA 3 and 5 a CRA 1 or 2. At second-look arthroscopy, 52 (91.3%) of all cartilage defects showed a normal or nearly normal macroscopic articular cartilage regeneration after arthroscopic ACI using spheroides. Twenty-four patients (77.4%) showed good subjective clinical results. The high number of concomitant surgery reflexes the complex aetiology of cartilage lesions and complexity of treatment. Thus, a strict indication and surgical planing is necessary to avoid clinical failures. IV.

Arthroscopic autologous chondrocyte implantation in the ankle joint

Autologous chondrocyte implantation (ACI) is an established procedure in the ankle providing satisfactory results. The development of a completely arthroscopic ACI procedure in the ankle joint made the technique easier and reduced the morbidity. The purpose of this investigation was to report the clinical results of a series of patients who underwent arthroscopic ACI of the talus at a mean of 7 ± 1.2-year follow-up. Forty-six patients (mean age 31.4 ± 7.6) affected by osteochondral lesions of the talar dome (OLT) received arthroscopic ACI between 2001 and 2006. Patients were clinically evaluated using AOFAS score pre-operatively and at 12, 36 months and at final follow-up of 87.2 ± 14.5 months. The mean pre-operative AOFAS score was 57.2 ± 14.3. At the 12-month follow-up, the mean AOFAS score was 86.8 ± 13.4 (p = 0.0005); at 36 months after surgery, the mean score was 89.5 ± 13.4 (p = 0.0005); whereas at final follow-up of 87.2 ± 14.5 months it was 92.0 ± 11.2 (p = 0.0005). There were three failures. Histological and immunohistochemical evaluations of specimens harvested from failed implants generally showed several aspects of a fibro-cartilaginous tissue associated with some aspects of cartilage tissue remodelling as indicated by the presence of type II collagen expression. This study confirmed the ability of arthroscopic ACI to repair osteochondral lesions in the ankle joint with satisfactory clinical results after mid-term follow-up. IV, retrospective case series.

Articular Cartilage Treatment in High-Level Male Soccer Players: A Prospective Comparative Study of Arthroscopic Second-Generation Autologous Chondrocyte Implantation Versus Microfracture

Articular Cartilage Treatment in High-Level Male Soccer Players: A Prospective Comparative Study of Arthroscopic Second-Generation Autologous Chondrocyte Implantation Versus Microfracture

Second-generation arthroscopic autologous chondrocyte implantation for the treatment of degenerative cartilage lesions

Degenerative cartilage lesions present a negative joint environment, which may have a negative effect on the process of cartilage regeneration. The aim of this study is to analyze the clinical outcome obtained with the treatment for isolated degenerative knee cartilage lesions by second-generation arthroscopic autologous chondrocyte implantation (ACI). Fifty-eight consecutive patients affected by focal degenerative chondral lesions of the femoral condyles and trochlea were treated by second-generation arthroscopic ACI. The mean age at surgery was 34.7 ± 9.1 years and the average defect size was 2.3 ± 0.9 cm(2). The patients were prospectively evaluated with IKDC, EQ-VAS, and Tegner scores preoperatively, at 2 and 6 years. A statistically significant improvement was observed in all scores from the basal evaluation to the final follow-up. The IKDC subjective score improved from 39.3 ± 13.6 to 68.8 ± 22.7 and 68.5 ± 23.9 at the 2- and 6-year follow-ups, respectively, with a significant improvement (P < 0.0005) and stable results over time; the same trend was confirmed by the EQ-VAS and Tegner scores. The worst results were found in patients with a low physical activity level, women, and those having undergone previous surgery, whereas the symptom duration before surgery did not influence the final outcome. The failure rate was 18.5%. Despite a significant improvement, the results were lower with respect to the outcome reported in different study populations, and the number of failures was markedly higher, too. Tissue-engineered cartilage implantation is a promising approach for the treatment of degenerative chondral lesions, but graft properties, besides mechanical and biochemical joint environment, have to be improved. Case series, Level IV.

Cartilage repair evolution in post-traumatic osteochondral lesions of the talus: From open field autologous chondrocyte to bone-marrow-derived cells transplantation

The aims of this study are to describe evolution in cartilage repair from open field autologous chondrocyte implantation to regeneration by arthroscopic bone-marrow-derived cells (BMDCs) “one step” technique; to present the results of a series of patients consecutively treated and to compare in detail the different techniques used in order to establish the advantages obtained with the evolution in cartilage regenerative methods. 81 patients (mean age 30 ± 8 years) were evaluated in this study. Patient assessment included clinical AOFAS score, X-rays and MRI preoperatively and at different established follow-ups. All the lesions were >1.5 cm 2 and received open autologous chondrocyte implantation (10 cases), arthroscopic autologous chondrocyte implantation (46 cases), and “one step” arthroscopic repair by BMDC transplantation (25 cases). For arthroscopic repair techniques a hyaluronic acid membrane was used to support cells and specifically designed instrumentation was developed. Patients of all the three groups underwent a second arthroscopy with a bioptic cartilage harvest at 1 year follow-up. Mean AOFAS score before surgery was 57.1 ± 17.2 and 92.6 ± 10.5 ( P < 0.0005) at mean 59.5 ± 26.5 months. A similar pattern of AOFAS improvement in results was found in the three different techniques. Histological evaluations highlighted collagen type II and proteoglycan expression. The cartilage repair techniques described were able to provide a repair tissue which closely approximates the characteristics of the naive hyaline cartilage. Evolution in surgical technique, new biomaterials and more recently the use of BMDCs permitted a marked reduction in procedure morbidity and costs up to a “one step” technique able to overcome all the drawbacks of previous repair techniques.

Autologous Chondrocyte Implantation

The purpose of the present study was to determine (1) whether the current literature supports the choice of using autologous chondrocyte implantation over other cartilage procedures with regard to clinical outcome, magnetic resonance imaging, arthroscopic assessment, and durability of treatment, (2) whether the current literature supports the use of a specific generation of autologous chondrocyte implantation, and (3) whether there are patient-specific and defect-specific factors that influence outcomes after autologous chondrocyte implantation in comparison with other cartilage repair or restoration procedures. We conducted a systematic review of multiple databases in which we evaluated Level-I and II studies comparing autologous chondrocyte implantation with another cartilage repair or restoration technique as well as comparative intergenerational studies of autologous chondrocyte implantation. The methodological quality of studies was evaluated with use of Delphi list and modified Coleman methodology scores. Effect size analysis was performed for all outcome measures. Thirteen studies (917 subjects) were included. Study methodological quality improved with later publication dates. The mean modified Coleman methodology score was 54 (of 100). Patients underwent autologous chondrocyte implantation (n = 604), microfracture (n = 271), or osteochondral autograft (n = 42). All surgical techniques demonstrated improvement in comparison with the preoperative status. Three of seven studies showed better clinical outcomes after autologous chondrocyte implantation in comparison with microfracture after one to three years of follow-up, whereas one study showed better outcomes two years after microfracture and three other studies showed no difference in these treatments after one to five years. Clinical outcomes after microfracture deteriorated after eighteen to twenty-four months (in three of seven studies). Autologous chondrocyte implantation and osteochondral autograft demonstrated equivalent short-term clinical outcomes, although there was more rapid improvement after osteochondral autograft (two studies). Although outcomes were equivalent between first and second-generation autologous chondrocyte implantation and between open and arthroscopic autologous chondrocyte implantation, complication rates were higher with open, periosteal-cover, first-generation autologous chondrocyte implantation (four studies). Younger patients with a shorter preoperative duration of symptoms and fewer prior surgical procedures had the best outcomes after both autologous chondrocyte implantation and microfracture. A defect size of >4 cm(2) was the only factor predictive of better outcomes when autologous chondrocyte implantation was compared with a non-autologous chondrocyte implantation surgical technique. Cartilage repair or restoration in the knee provides short-term success with microfracture, autologous chondrocyte implantation, or osteochondral autograft. There are patient-specific and defect-specific factors that influence clinical outcomes.

Does Intensive Rehabilitation Permit Early Return to Sport without Compromising the Clinical Outcome after Arthroscopic Autologous Chondrocyte Implantation in Highly Competitive Athletes?

Background Despite improvement in treatment for articular cartilage lesions, prolonged recovery still precludes early return to competitive sports. The challenge of postoperative rehabilitation is to optimize return to preinjury activities without jeopardizing the graft. Hypothesis Intensive rehabilitation after second-generation arthroscopic autologous cartilage implantation (Hyalograft C) facilitates graft maturation and safely allows for early return to competition without jeopardizing clinical outcome at longer follow-up. Study Design Cohort study; Level of evidence, 3. Methods The outcome of 31 competitive male athletes with International Cartilage Repair Society grade III-IV cartilaginous lesions of the medial or lateral femoral condyle or trochlea were evaluated at 1-, 2-, and 5-year follow-up. The athletic cohort was compared with a similar control cohort of 34 nonathletic patients who were treated with autologous chondrocyte implantation. The athletic cohort followed a 4-phase intensive rehabilitation protocol. Eleven of the patients in this cohort were also treated with an isokinetic exercise program and on-field rehabilitation. The patients in the control cohort completed only phase 1 of rehabilitation. Results When comparing the 2 groups, a greater improvement in the group of athletes was achieved at 5-year follow-up (P = .037) in the self-assessment of quality of life and International Knee Documentation Committee subjective evaluation at 12 months and at 5 years of follow-up (P = .001 and P = .002, respectively). When analyzing the return to sports activity, 80.6% of the athletes returned to their previous activity level in 12.4 ± 1.6 months; athletes treated with the on-field rehabilitation and isokinetic exercise program had faster recovery and an even earlier return to competition (10.6 ± 2.0 months). Conclusion For optimal results, autologous chondrocyte implantation rehabilitation should not only follow but also facilitate the process of graft maturation. Intensive rehabilitation may safely allow a faster return to competition and also influence positively the clinical outcome at medium-term follow-up.

Autologous Chondrocyte Implantation in the Knee Joint: Open Compared with Arthroscopic Technique

Autologous chondrocyte implantation is a widely used technique for treating cartilage lesions1-10. The technique, first introduced and described by Brittberg et al. in 199411, required an arthrotomy of the joint, debridement of the lesions, and the suturing of a periosteal flap to create a pocket to host the chondrocytes. Autologous chondrocyte implantation in the knee joint has provided hyaline-like repair tissue11-16, with satisfactory clinical results in 80% to 90% of patients1,7,17. Moreover, autologous chondrocyte implantation has been shown to be a valid alternative to the mosaicplasty and microfracture repair techniques used in the treatment of osteochondral lesions of the knee1,6,13,17-20. In the recent past, to simplify the autologous chondrocyte implantation surgical technique, a three-dimensional hyaluronic acid scaffold was developed to support the autologous chondrocytes13. This scaffold enables an arthroscopic implantation technique to be used21. Furthermore, the chondrocytes embedded on the hyaluronic acid scaffold tend to maintain their original phenotype22 with respect to dedifferentiation induced by the fluid medium23. Despite initial encouraging results with the use of arthroscopic autologous chondrocyte implantation in the treatment of osteochondral lesions of the knee24-26, open and arthroscopic autologous chondrocyte implantation techniques have been compared in only a few studies23,25,26, and these have included only short-term follow-up and limited and nonhomogeneous case series. The aim of this study was to compare the long-term results in two groups of patients in whom osteochondral lesions in the knee joint were treated with the two aforementioned procedures. Patients were evaluated clinically, histologically, and with magnetic resonance imaging, with a minimum five-year follow-up. Between 1997 and 2002, …

Arthroscopic Autologous Chondrocyte Implantation in Osteochondral Lesions of the Talus

Background Autologous chondrocyte implantation (ACI) in the ankle was considered up to now an extremely technically demanding surgery with considerable morbidity for the patients. Hypothesis Hyalograft C scaffold allows arthroscopic ACI, thanks to a specifically designed instrumentation. Study Design Case series; Level of evidence, 4. Methods Forty-six patients with a mean age of 31.4 years (range, 20–47) underwent operation from 2001 to 2004. They had posttraumatic talar dome lesions, type II or IIA. In the first step of surgery, an ankle arthroscopy was performed, with cartilage harvest from the detached osteochondral fragment or from the margins of the lesion. Chondrocytes were cultured on a Hyalograft C scaffold. In the second step of surgery, the Hyalograft C patch was arthroscopically implanted into the lesion, with a specifically designed instrumentation. Lesions >5 mm deep were first filled with autologous cancellous bone. Patients were evaluated clinically with the American Orthopaedic Foot and Ankle Society (AOFAS) score preoperatively and at 12 and 36 months after surgery. At a mean time interval of 18 months, the first 3 patients underwent a second-look arthroscopy with cartilage harvest from the implant and histological examination. Results The mean preoperative AOFAS score was 57.2 ± 14.3. At the 12-month follow-up, the mean AOFAS score was 86.8 ± 13.4 (P < .0005), while at 36 months after surgery, the mean score was 89.5 ± 13.4 (P < .0005). Clinical results were significantly related to the age of patients and to previous operations for cartilage repair. The results of the histological examinations revealed hyaline-like cartilage regeneration. Conclusions The Hyalograft C scaffold and the specifically designed instrumentation allowed arthroscopic implantation of chondrocytes, with excellent clinical and histological results.

Management of Patellar and Trochlear Chondral Injuries

Patellofemoral chondral injuries are noted in a significant subset of patients with anterior knee pain. These injuries occur as a result of both acute traumatic events and chronic patellofemoral malalignment. Focal grade III and IV chondral defects of the patella or trochlea present a significant management challenge. Anatomic factors, including an increased quadriceps angle, tight lateral retinaculum and weakened vastus medialis oblique muscle produce maltracking, which results in overload of the lateral patellofemoral joint. Patella alta, trochlear dysplasia and hyperlaxity can result in patellofemoral instability and subluxation. These factors play a role in the development of patellofemoral chondral injuries and must be addressed. A trial of 6 months of conservative management is indicated for most patients. Surgical options often include a realignment procedure in addition to treatment of the chondral injury. Traditional cartilage resurfacing techniques including debridement, abrasion arthroplasty and microfracture have been used but are limited by the inferior wear characteristics of the fibrocartilage tissue which forms over the defect. Newer cartilage repair techniques include autologous chondrocyte implantation and osteochondral autograft transfer (mosaicplasty) attempt to repair the chondral defect with hyaline cartilage. Osteochondral allograft transfer is an option for large chondral defects in which the surface contour of the patella or trochlea has been lost. Patellofemoral arthroplasty may be superior to total knee arthroplasty in patients with isolated patellofemoral joint collapse. Newer techniques such as arthroscopic autologous chondrocyte implantation using biologic scaffolds in place of the periosteal cover are currently being investigated.

22.1 Arthroscopic second generation autologous chondrocyte implantation at 48 months follow-up

22.1 Arthroscopic second generation autologous chondrocyte implantation at 48 months follow-up

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-cm 2 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.