Autologous chondrocyte implantation is now a recognised treatment for patients with knee pain secondary to articular cartilage defects. The initial technique involving periosteum as the cover for the implanted cells (ACI-P) has been modified to the use of a type I/III collagen membrane (ACI-C). Matrix-induced Autologous Chondrocyte Implantation (MACI) is a technique in which autologous donor chondrocytes are implanted onto the collagen membrane and then fixed into the defect with fibrin glue. We performed a prospective randomised comparison of 247 patients (126 ACI and 121 MACI). Patients' pain and function were assessed with mean follow-up of 42 months. Function was measured using the Modified Cincinnati and Stanmore Scoring systems. Arthroscopic assessment was by the ICRS classification. The influence of the size and site of the lesion, sex, age and previous knee surgery on the results was analysed. The Modified Cincinnati score showed a mean 17.5 point rise from pre-operative scores in the ACI group and 19.6 point rise in the MACI group. Pain, measured using the Visual Analogue Score, showed an improvement in both arms of the trial. Both chondrocyte implantation methods showed improvement in 86% of patients clinically and arthroscopically, with excellent and good results in 50% and fair results in 30% of patients. 20% of patients showed no improvement in function but none were worse. There were no serious complications. Limited histological analysis showed hyaline cartilage in a higher but non-significant proportion of ACI-C cases. With over 11 years' experience in the use of both forms of cartilage implantation we have established more precisely the indications for chondrocyte implantation. Although MACI is technically a more attractive option in most cases, because of ease and speed of the procedure, longer term follow-up is required to assess the longevity of ACI-C and MACI and the effect on prevention of ‘early-onset’ Osteoarthritis

Introduction. We report the initial 2 and 3 year follow-up results of this randomised controlled trial of autologous chondrocyte implantation (ACI) using porcine-derived collagen membrane as a cover (ACI-C) versus matrix-carried autologous chondrocyte implantation (MACI) for the treatment of osteochondral defects of the knee. Methods. 217 patients were randomised to have either ACI (92 patients) or MACI (125 patients). The mean age in each group was 35.1 and 33 years respectively. There were equal proportion of males and females and there was no difference in the size of lesions in each of the treatment groups. One year following surgery, patients underwent check arthroscopy (with or without biopsy) to assess the graft. Functional assessment was performed yearly by using the Modified Cincinatti Knee score, the SF-36 score, the Bentley Functional Rating Score and the Visual Analogue Score. Results. 32 patients (27 from the MACI group) were excluded from the study as they underwent additional procedures (e.g. high tibial osteotomy). In the ACI group the modified Cincinnati score increased from 45.2 pre-operatively to 56.7, 54.1, and 65.4 at 1 year, 2 years and 3 years respectively. In the MACI group the Cincinnati scores increased from 45.5 pre-operatively to 59.9, 58.9, and 63.4. Arthroscopic assessment showed a good to excellent International Cartilage Repair Society score in 91.4% of ACI-C grafts and 76.1% of MACI grafts. Hyaline-like cartilage or hyaline-like with fibrocartilage was found in biopsies of 48.6% of ACI-C grafts and 30.5% of MACI grafts. Conclusions. ACI grafts are more likely to produce hyaline-like or mixed hyaline-like cartilage and fibrocartilage with better ICRS grades than MACI grafts. However, this does not translate to a better functional outcome. More importantly, ACI and MACI had similar results that were maintained at 3 years

Purpose. We report on minimum 2 year follow-up results of 71 patients randomised to autologous chondrocyte implantation (ACI) using porcine-derived collagen membrane as a cover (ACI-C) and matrix-induced autologous chondrocyte implantation (MACI) for the treatment of osteochondral defects of the knee. Introduction. ACI is used widely as a treatment for symptomatic chondral and osteochondral defects of the knee. Variations of the original periosteum-cover technique include the use of porcine-derived type I/type III collagen as a cover (ACI-C) and matrix-induced autologous chondrocyte implantation (MACI) using a collagen bilayer seeded with chondrocytes. Results. 71 patients with a mean age of 33 years (15-48) were randomised to undergo either an ACI-C or a MACI. 37 had ACI-C and 34 MACI. The mean size of the defect was 5.0cm2. Mean duration of symptoms was 104.4 months (9-456). Mean follow-up was 33.5 months (24-45). Functional assessment using the modified Cincinnati knee score, the Bentley functional rating score and the visual analogue score was carried out. Assessment using the modified Cincinnati knee score showed a good to excellent result in 57.1% of patients followed up at 2 years, and 65.2% at 3 years in the ACI-C group; and 63.6% of patients at 2 years, and 64% at 3 years in the MACI group. Arthroscopic assessments showed a good to excellent International Cartilage Repair Society score in 81.8% of ACI-C grafts and 50% of MACI grafts. Hyaline-like cartilage or hyaline-like cartilage with fibrocartilage was found in biopsies of 56.3% of the ACI-C grafts and 30% of the MACI grafts after 2 years. Conclusion. At this stage of the trial we conclude that the clinical, arthroscopic and histological outcomes are comparable for both ACI-C and MACI

Introduction. The treatment of distal femoral cartilage defects using autologous chondrocyte implantation (ACI) and matrix-guided autologous chondrocyte implantation (MACI) is become increasingly common. This prospective 7-year study reviews and compares the clinical outcome of ACI and MACI. Methods. We present the clinical outcomes of 159 knees (156 patients) that have undergone autologous chondrocyte implantation from July 1998. One surgeon performed all operations with patients subsequently assessed on a yearly basis using 7 independent validated clinical, functional and satisfaction rating scores. Results. Modified Cincinnati, Patient Functional Outcome and Lysholm & Gilchrist clinical rating scores all showed significant improvements compared to pre-operative levels (p<0.0001). Although ACI scores are superior at one year (p<0.05) there is no significant difference between ACI and MACI at 2 years. Visual Analogue Score and Bentley Functional rating score showed significant improvements compared to pre-operative levels (p<0.0001) with ongoing yearly sequential improvement. Patient Rating and Brittberg scores, both subjective patient scores, similarly showed continuing improvements in the years following surgery. Discussion. ACI and MACI produce significant improvements in knee function when compared to pre-operative levels with continued sequential improvement in outcomes for up to seven years. The initial data suggests a superior rate of clinical improvement using the MACI technique

The treatment of osteochondral lesions in the ankle joint remains a challenging problem. While debridement and drilling or microfracture of the lesion reduce symptoms initially, long-term stability of the fibrous repair tissue is questionable. Osteochondral transplantation or mosaicplasty provide hyaline cartilage and repair the bony defect at the same time. However, an open arthrotomy with medial, lateral or anterior osteotomy is necessary to repair lesions of the talus. Lesions of the distal tibia cannot be reached. Matrix Associated Chondrocyte Implantation (MACI) has been shown to produce hyaline like cartilage repair tissue, and the implantation can be performed arthroscopically. Long term follow up studies (up to 10 years) in the knee demonstrate promising results. The purpose of this study was to assess the efficacy of arthroscopic MACI for the treatment of osteochondral lesions in the ankle joint. We reviewed all patients (n=20) who had arthroscopic MACI treatment (n=22) between February 2006 and November 2008 clinically (Foot Function Index, AAOS Foot and Ankle Questionnaire, AOFAS-Hindfoot Score) and with MRI (3 Tesla Siemens MRI). The clinical results and MRI findings up to three years after MACI were compared to pre-operative data. Possible correlations with the individual history and the nature, size or location of the lesion will be discussed. The surgical technique will be described. The results of the procedure are promising

Objective. To investigate the histological and immunohistochemical characteristics of revised and failed MACI repair tissues. Methods. We examined the matrix profiles of repair biopsies taken from revised and clinically failed MACI cases by semi-quantitative immunohistochemical study using antibodies specific to aggrecan, collagens I, II, III, VI, and IX, Sox-9, Ki-67 and MMP-13. We also stiffness tested an intact clinically failed repair site. Results. Histologically, the majority of these biopsies (n=39) were hyaline-like (HLC) and fibrocartilage (FC) in both the revised (30% and 38% respectively) and failed (34% and 22% respectively) cases. Compositionally, more revised cases were positive for aggrecan, collagens VI and IX, and Ki67 compared to failed cases, but not quantitatively different (P>0.05). More HLC biopsies were positive for aggrecan and collagen II (compared to the FC group), with diffuse and often colocalized matrix distribution. The majority of HLC biopsies stained positive for Sox-9, whereas FC cases were negative. Most (75%) FC biopsies were positive for Ki-67, compared to the HLC group with 25%. MMP-13 was negative in all biopsies. Qualitatively, reduced collagen II and IX, and increased Ki67 production was noted in FC biopsies (P<0.05). An intact repair site showed FC with 30% greater stiffness in the inferior portion compared to the superior, with an associated proteoglycan content increase. Conclusions. Revised and failed biopsies display predominantly fibrocartilage and hyaline-like cartilage and are histologically dissimilar to healthy cartilage, but do not differ in composition. Hyaline-like repairs show lower proliferation but improved matrix to fibrocartilage repairs. Our study furthers knowledge into failed and revised cartilage repair by MACI

This study investigated confocal laser scanning microscopy (CLSM) as a novel method of imaging of chondrocytes on a collagen membrane used for articular cartilage repair. Cell viability and the effects of surgery on the cells were assessed. Cell images were acquired under four conditions: 1, Pre-operative 2, After handling 3, Heavily grasped with forceps 4, Cut around the edge. Live and dead cell stains were used. Images were obtained for cell counting and morphology. Mean cell density was 1.12–1.68 ± 0.22 × 10. 6. cells/cm. 2. in specimens without significant trauma (n=25 images), this decreased to 0.253 × 10. 6. cells/cm. 2. in the specimens that had been grasped with forceps (p <0.001) (5 images). Cell viability on delivery grade membrane was 86.8±2.1%. The viability dropped to 76.3 ± 1.6% after handling and 35.1 ± 1.7% after crushing with forceps. Where the membrane was cut with scissors, there was a band of cell death where the viability dropped to 17.3 ± 2.0% compared to 73.4 ± 1.9% in the adjacent area (p <0.001). Higher magnification revealed cells did not have the rounded appearance of chondrocytes. CLSM can quantify and image the fine morphology of cells on a MACI membrane. Careful handling of the membrane is essential to minimise chondrocyte death during surgery

Over recent years chondrocyte implantation (MACI) has become a recognised procedure. This paper presents the results of two players in the national rugby league competition who play first grade football and have undergone the procedure. Professional sports medical care can be difficult. Demands from players, the public and coaches are beyond our normal requirements as surgeons. Faced with two high-profile players with career ending focal grade 4 chondral lessions and not responding to our normal treatment methods, I performed chondrocyte implantation (MACI) to deal with this. Both players have responded well to treatment and returned to first grade football. The two players in question had focal grade 4 chondral lesions. They had not responded to treatment and had recurrent effusions restricting their ability to play. Player A required a revision acl reconstruction as he was to be away from the game for a year. I treated his chondral lesion with MACI. His effusion settled and he returned to play with no further delays other than those expected from the acl surgery. Encouraged by this result, I performed the second procedure on a very high- profile player who had recurrent pain and effusion and had been treated with arthroscopies with little improvement. Faced with retirement, he opted for the procedure and returned to first grade the following season

Purpose. Osteochondral lesions (OCL) of the talus remain a challenging therapeutic task to orthopaedic surgeons. Several operative techniques are available for treatment, e.g. autologous chondrocyte implantation (ACI), osteochondral autograft transfer system (OATS), matrix-induced autologous chondrocyte implantation (MACI). Good early results are reported; however, disadvantages are sacrifice of healthy cartilage of another joint or necessity of a two-stage procedure. This case describes a novel, one-step operative treatment of OCL of the talus utilizing the autologous matrix-induced chondrogenesis (AMIC) technique in combination with a collagen I/III membrane. Method. 20 patients (8 female, 12 male; mean age 36, range 17–55 years) were assessed in our outpatient clinic for unilateral OCL of the talus. Preoperative assessment included the AOFAS hindfoot scale, conventional radiography, magnetresonancetomography (MRI) and SPECT-CT. Surgical procedure consisted of debridement of the OCL, spongiosa plasty from the iliac crest and coverage with the I/III collagen membrane (Chondrogide, Geistlich Biomaterials, Wolhusen, Switzerland). Clinical and radiological followup was performed after one year. Results. The mean preoperative AOFAS hindfoot scale was poor with 63.1 points (SD 19.6). At one year followup the score improved significantly (p<0.01) to 86 points (SD 12). At one year followup conventional radiographs showed osseous integration of the graft in all cases. MRI at one year showed intact cartilage covering the lesions in all cases. Conclusion. The initial results of this ongoing study are encouraging. The clinical and radiological results at one year followup are comparable with the results of ACI, OATS and MACI. The AMIC procedure is a readily available, economically efficient, one step surgical procedure. No culturing after chondrocyte harvesting or destruction of viable cartilage is necessary

Purpose. Traumatic articular cartilage (AC) defects are common in young adults and frequently progresses to osteoarthritis. Matrix-Induced Autologous Chondrocyte Implantation (MACI) is a recent advancement in cartilage resurfacing techniques and is a variant of ACI, which is considered by some surgeons to be the gold standard in AC regeneration. MACI involves embedding cultured chondrocytes into a scaffold that is then surgically implanted into an AC defect. Unfortunately, chondrocytes cultured in a normoxic environment (conventional technique) tend to de-differentiate resulting in decreased collagen II and increased collagen I producing in a fibrocartilagous repair tissue that is biomechanically inferior to AC and incapable of withstanding physiologic loads over prolonged periods. The optimum conditions for maintenance of chondrocyte phenotype remain elusive. Normal oxygen tension within AC is <7%. We hypothesized that hypoxic conditions would induce gene expression and matrix production that more closely characterizes normal articular chondrocytes than that achieved under normoxic conditions when chondrocytes are cultured in a collagen scaffold. Method. Chondrocytes were isolated from Outerbridge grade 0 and 1 AC from four patients undergoing total knee arthroplasty and embedded within 216 bovine collagen I scaffolds. Scaffolds were incubated in hypoxic (3% O2) or normoxic (21% O2) conditions for 1hr, 21hr and 14 days. Gene expression was determined using Q-rt-PCR for col I/II/X, COMP, SOX9, aggrecan and B actin. Matrix production was determined using glycosaminoglycan (GAG) content relative to cell count determined by DNA quantification. Cell viability and location within the matrix was determined by Live/Dead assay and confocal microscopy. Statistical analysis was performed using a two-tailed T-test. Results. Chondrocytes cultured under hypoxic conditions showed an upregulation of all matrix related genes compared to normoxic conditions noted most markedly in col II, COMP and SOX9 expression. There were similar numbers of chondrocytes between hypoxic and normoxic groups (P=0.68) but the chondrocytes in the hypoxic group produced more GAG per cell (P= 0.052). Viable cells were seen throughout the matrix in both groups. Conclusion. Important matrix related genes (col II, COMP, SOX9) were most significantly upregulated in hypoxic conditions compared to normoxic conditions. This was supported by an increase in GAG production per cell in hypoxic conditions. The results indicate that hypoxia induces an upregulation in the production of extracellular matrix components typical of AC with only modest increases in col I (possibly related to the col I based scaffold used in this experiment). These results indicate that hypoxic conditions are important for the maintenance of chondrocyte phenotype even when the cells are cultured in a 3D environment. In conclusion, hypoxic culture conditions should be used to help maintain chondrocyte phenotype even when culturing these cells in a 3D scaffold