Chondral injuries of the knee are extremely common and present a unique therapeutic challenge due to the poor intrinsic healing of articular cartilage. These injuries can lead to significant functional impairment. There are several treatment modalities for articular osteochondral defects, one of which is autologous chondrocyte implantation. Our study evaluates the mid to long term functional outcomes in a cohort of 828 patients who have undergone an autologous chondrocyte implantation procedure (either ACI or MACI), identifying retrospectively factors that may influence their outcome. The influence of factors including age, sex, presence of osteoarthritis and size and site of lesion have been assessed individually and with multivariate analysis. All patients were assessed using the Bentley Functional Score, Visual Analogue Score and the Cincinnati Functional Score. Assessment were performed pre-operatively and of their status in 2010. The longest follow-up was 12 years (range 24 to 153 months) with a mean age of 34 years at time of procedure. The mean defect size was 409 mm. 2. (range 64 to 2075 mm. 2. ). The distribution of lesions was 51% Medial Femoral Condyle, 12.5% Lateral Femoral Condyle, 18% Patella (single facet), 5% Patella (Multifacet) and 6% Trochlea. 4% had cartilage transplant to multiple sites. High failure rates were noted in those with previous cartilage regenerative procedures or evidence of early osteoarthritis and those with transplantation to multiple sites. Autologous chondrocyte implantation is an effective method of decreasing pain and increasing function, however patient selection plays clear role in the success of such procedure

Abstract. Introduction. Autologous chondrocyte implantation (ACI) is a common procedure, primarily performed in active, young patients to treat knee pain and functional limitations resulting from cartilage injury. Nevertheless, the functional outcomes of ACI remain poorly understood. Thus, the aim of this systematic review was to evaluate the biomechanical outcomes of ACI. Methodology. Ovid MEDLINE, Embase, and Web of Science were systematically searched using the terms ‘Knee OR Knee joint AND Autologous chondrocyte implantation OR ACI’. Strict inclusion and exclusion criteria were used to screen publications by title, abstract, and full text. Study quality and bias were assessed by two reviewers. PROSPERO ID: CRD42021238768. Results. 28 articles including 35 ACI cohorts were included in this review. The average range of motion (ROM) was found to improve with clinical significance (>5˚) and statistical significance (p < 0.05) postoperatively: 133.9 ± 5.5˚ to 139.2 ± 4.9˚ (n=12). Knee strength significantly improved within the first two postoperative years, but remained poorer than control groups at final follow-up (n=17). No statistical differences were found between ACI and control groups in their ability to perform functional activities like the 6-minute walk test. However, peak external knee extension and adduction moments during gait were significantly poorer in ACI patients when compared to controls. Conclusion. Generally, functional outcomes improved with clinical and statistical significance following ACI. However, knee strengths and external knee moments during gait remain significantly poorer than healthy controls, particularly >2-years postoperatively. Thus, ACI patients likely require targeted strength training as part of their rehabilitation programme

Aims. Autologous chondrocyte implantation (ACI) is a promising treatment for articular cartilage degeneration and injury; however, it requires a large number of human hyaline chondrocytes, which often undergo dedifferentiation during in vitro expansion. This study aimed to investigate the effect of suramin on chondrocyte differentiation and its underlying mechanism. Methods. Porcine chondrocytes were treated with vehicle or various doses of suramin. The expression of collagen, type II, alpha 1 (COL2A1), aggrecan (ACAN); COL1A1; COL10A1; SRY-box transcription factor 9 (SOX9); nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX); interleukin (IL)-1β; tumour necrosis factor alpha (TNFα); IL-8; and matrix metallopeptidase 13 (MMP-13) in chondrocytes at both messenger RNA (mRNA) and protein levels was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot. In addition, the supplementation of suramin to redifferentiation medium for the culture of expanded chondrocytes in 3D pellets was evaluated. Glycosaminoglycan (GAG) and collagen production were evaluated by biochemical analyses and immunofluorescence, as well as by immunohistochemistry. The expression of reactive oxygen species (ROS) and NOX activity were assessed by luciferase reporter gene assay, immunofluorescence analysis, and flow cytometry. Mutagenesis analysis, Alcian blue staining, reverse transcriptase polymerase chain reaction (RT-PCR), and western blot assay were used to determine whether p67. phox. was involved in suramin-enhanced chondrocyte phenotype maintenance. Results. Suramin enhanced the COL2A1 and ACAN expression and lowered COL1A1 synthesis. Also, in 3D pellet culture GAG and COL2A1 production was significantly higher in pellets consisting of chondrocytes expanded with suramin compared to controls. Surprisingly, suramin also increased ROS generation, which is largely caused by enhanced NOX (p67. phox. ) activity and membrane translocation. Overexpression of p67. phox. but not p67. phox. AD (deleting amino acid (a.a) 199 to 212) mutant, which does not support ROS production in chondrocytes, significantly enhanced chondrocyte phenotype maintenance, SOX9 expression, and AKT (S473) phosphorylation. Knockdown of p67. phox. with its specific short hairpin (sh) RNA (shRNA) abolished the suramin-induced effects. Moreover, when these cells were treated with the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) inhibitor LY294002 or shRNA of AKT1, p67. phox. -induced COL2A1 and ACAN expression was significantly inhibited. Conclusion. Suramin could redifferentiate dedifferentiated chondrocytes dependent on p67. phox. activation, which is mediated by the PI3K/AKT/SOX9 signalling pathway. Cite this article: Bone Joint Res 2022;11(10):723–738

Aims. The aim of this retrospective study was to determine if there are differences in short-term clinical outcomes among four different types of matrix-associated autologous chondrocyte transplantation (MACT). Methods. A total of 88 patients (mean age 34 years (SD 10.03), mean BMI 25 kg/m. 2. (SD 3.51)) with full-thickness chondral lesions of the tibiofemoral joint who underwent MACT were included in this study. Clinical examinations were performed preoperatively and 24 months after transplantation. Clinical outcomes were evaluated using the International Knee Documentation Committee (IKDC) Subjective Knee Form, the Brittberg score, the Tegner Activity Scale, and the visual analogue scale (VAS) for pain. The Kruskal-Wallis test by ranks was used to compare the clinical scores of the different transplant types. Results. The mean defect size of the tibiofemoral joint compartment was 4.28 cm. 2. (SD 1.70). In total, 11 patients (12.6%) underwent transplantation with Chondro-Gide (matrix-associated autologous chondrocyte implantation (MACI)), 40 patients (46.0%) with Hyalograft C (HYAFF), 21 patients (24.1%) with Cartilage Regeneration System (CaReS), and 15 patients (17.2%) with NOVOCART 3D. The mean IKDC Subjective Knee Form score improved from 35.71 (SD 6.44) preoperatively to 75.26 (SD 18.36) after 24 months postoperatively in the Hyalograft group, from 35.94 (SD 10.29) to 71.57 (SD 16.31) in the Chondro-Gide (MACI) group, from 37.06 (SD 5.42) to 71.49 (SD 6.76) in the NOVOCART 3D group, and from 45.05 (SD 15.83) to 70.33 (SD 19.65) in the CaReS group. Similar improvements were observed in the VAS and Brittberg scores. Conclusion. Two years postoperatively, there were no significant differences in terms of outcomes. Our data demonstrated that MACT, regardless of the implants used, resulted in good clinical improvement two years after transplantation for localized tibiofemoral defects. Cite this article: Bone Joint Res 2021;10(7):370–379

Abstract. Background. Autologous chondrocyte implantation is a NICE approved intervention however it involves the morbidity of two operations, a prolonged rehabilitation and substantial healthcare costs. This study describes a novel, one-step, bone marrow (BM) derived mesenchymal stem cell (MSC) transplantation technique for treating knee osteochondral lesions and presents our prospective clinical study investigating the success of this technique in 206 lesions over a 5 year period. Methodology. The surgical technique involves harvesting BM from patients’ anterior superior iliac spines, centrifugation to isolate MSCs and seeding into a type 1 collagen scaffold (SyngenitTM Biomatrix). Autologous fibrin glue is used to secure the scaffold into the defect. Inclusion criteria included patients aged 15 – 55 years old with symptomatic osteochondral lesions >1cm2. Exclusion criteria included patients with ligament instability, uncorrected alignment, inflammatory arthropathy and a Body Mass Index >35 kg/m2. Outcome measures included the Modified Cincinnati Knee Rating System (MCKRS), complications and reoperations. Results. Mean MCKR scores showed statistically significant improvements compared to pre-operative scores at 6 months 58.79 ± 3.5 and 1 year postoperatively 63.82 ± 3.93 with further improvements at 2 years and 5 years which did not reach statistical significance. Survival rates were 97.9%, 94% and 93.2% at 1, 2 and 5 years. Multiple regression analysis identified previous cartilage surgery, microfracture and age as factors affecting MCKRS scores (p < 0.029, 0.001 and 0.030, respectively). Conclusions. One-step BM derived stem cell transplantation demonstrates satisfactory outcomes over a 5 year period

Symptomatic articular cartilage defects are one of the most common knee injuries, arising from acute trauma, overuse, ligamentous instability, malalignment, meniscectomy, osteochondritis dissecans. Surgical treatment options include bone marrow–stimulating techniques such as abrasion arthroplasty and microfracture, osteochondral mosaicplasty, corrective osteotomy, cartilage resurfacing techniques and tissue engineering techniques using combinations of autologous cells (chondrocytes and mesenchymal stem cells), bioscaffolds, and growth factors. Matrix induced autologous chondrocyte implantation (MACI) is considered the most surgically simple form of autologous chondrocyte implantation. Our group has involved in the development of MACI since 2000 and has led to the FDA approval of MACI as the first tissue engineering product for cartilage repair in 2016. In this article, we have documented the characterisation of autologous chondrocytes, the surgical procedure of MACI and the long term clinical assessment (15 years) of patients with treatment of MACI. We have also reported the retrospective survey in patients with MACI in Australia. Our results suggest that MACI has gained good to excellent long term clinical outcome and probably can delay total knee replacement. However, restoration of hyaline-like cartilage by MACI may be interrupted by the osteoarthritic condition of the joint in patients with progressed osteoarthritis. In addition, because articular cartilage and subchondral bone are considered a single functional unit that is essential for joint function, many cartilage repair technologies including MACI and microfractures have failed short to address the functional barrier structure of osteochondral unit. Further studies are required to develop tissue engineering osteochondral construct that is able to fulfil the function of articular cartilage-subchondral bone units

Hypothesis. Cartilage defects pretreated with marrow stimulation techniques will have an increased failure rate. The first 321 consecutive patients treated at one institution with autologous chondrocyte implantation for full-thickness cartilage defects that reached more than two years of follow-up were evaluated by prospectively collected data. Patients were grouped based on whether they had undergone prior treatment with a marrow stimulation technique. Outcomes were classified as complete failure if more than 25% of a grafted defect area had to be removed in later procedures because of persistent symptoms. Results. There were 522 defects in 321 patients (325 joints) treated with autologous chondrocyte implantation. On average, there were 1.7 lesions per patient. Of these joints, 111 had previously undergone surgery that penetrated the subchondral bone; 214 joints had no prior treatment that affected the subchondral bone and served as controls. Within the marrow stimulation group, there were 29 (26%) failures, compared with 17 (8%) failures in the control group. Conclusion. Defects that had prior treatment affecting the subchondral bone failed at a rate three times that of nontreated defects. The failure rates for drilling (28%), abrasion arthroplasty (27%), and microfracture (20%) were not significantly different—possibly because of the lower number of microfracture patients in this cohort (25 of 110 marrow-stimulation procedures). The data demonstrate that marrow stimulation techniques have a strong negative effect on subsequent cartilage repair with autologous chondrocyte implantation and, therefore, should be used judiciously in larger cartilage defects that could require future treatment with autologous chondrocyte implantation. Unlike coventional wisdom, MSTs do ‘burn bridges’

The aim of this study was to determine whether the clinical outcome of autologous chondrocyte transplantation was dependent on the timing of a high tibial osteotomy in tibio-femoral mal-aligned knees. Between 2000 and 2005, forty-eight patients underwent autologous chondrocyte implantation with HTO performed at varying times relative to the second stage autologous chondrocyte implantation procedure. 24 patients had HTO performed simultaneously with their second stage cartilage transplantation, (the HTO Simultaneous Group). 5 patients had HTO prior to their cartilage procedure, (the HTO pre-ACI Group) and 19 had HTO performed between 1 to 4 years after their second stage cartilage implantation, (the HTO post-ACI Group). There were 29 men and 19 women with a mean age of 37 years (Range 28 to 50) at the time of their second stage procedure. With average follow-up of 72 months we have demonstrated a significant functional benefit in performing the HTO either prior to or simultaneously with the ACI procedure in the mal-aligned knee. The failure rate in the Post-ACI group was 45% compared to the Pre-ACI and Simultaneous group, with failure rates of 20% and 25%, respectively. An HTO performed prior to or simultaneously with an autologous chondrocyte implantation procedure in the mal-aligned knee, provides a significant protective effect by reducing the failure rate by approximately 50%

Introduction and Aims: The aim of this study was to use biological, functional and radiographic evaluation to demonstrate that cultured autologous chondrocytes implanted using a type I/III collagen membrane leads to regeneration of hyaline-like articular cartilage in the knee. Method: Approximately 70,000 knee arthroscopies are performed every year in Australia; 60% involve chondral surface defects. Three regenerative autologous cell therapy techniques have been used in Australia to treat full thickness chondral lesions:. periostial-covered autologous chondrocyte implantation (PACI);. collagen-covered autologous chondrocyte implantation (CACI);. matrix-induced autologous chondrocyte implantation (MACI). The team at the University of Western Australia has concentrated on CACI and MACI techniques because of concerns over fibroblast formation and hypertrophy with PACI. Definitive evidence regarding the role of the membrane in enhancing chondrocyte-mediated cartilage regeneration is lacking. Results: The series consists of a total of 71 patients who had failed previous surgical treatment prior to definitive collagen-covered ACI (32 implantations in 31 patients) or MACI (43 implantations in 40 patients). Biological, functional and radiographic evaluations were conducted pre-operatively, and post-operatively in order to determine the success of integration of implanted chondrocytes and categorise the level of restoration in knee joint function. Post-operative MRI scans at three months show oedematous tissue at the defect sites, contrasting with the fluid-filled defects seen pre-operatively. MRI scans at one, two and three years (collagen-covered) and one year (MACI) show normal cartilage signal. Apopototic test of chondrocytes before implantation showed that viability of chondrocytes was over 85% where apopototic rate of chondrocytes was less than 2%. Six-minute walk test and KOOS results indicate improved functional capacity following collagen covered and MACI. Conclusion: Results from this clinical study indicate that the use of a type I/III collagen membrane in conjunction with ACI is a valid new approach for the treatment of chondral defects. Results from radiographic, functional and biological evaluations are encouraging. Ongoing follow-up will reveal the durability of reconstructions with CACI and MACI

Abstract. Objective. Clinical treatments to repair articular cartilage (AC) defects such as autologous cartilage implantation (mosaicplasty) often suffer from poor integration with host tissue, limiting their long-term efficacy. Thus to ensure the longevity of AC repair, understanding natural repair mechanisms that allow for successful integration between cartilaginous surfaces, as has been reported in juvenile tissue, may be key. Here, we evaluated cartilage integration over time in a pig explant model of natural tissue repair by assessing expression and localisation of major ECM proteins, enzymatic cross-linkers including the five isoforms of lysyl oxidase (LOX), small leucine-rich repeat proteoglycans (SLRP's), and proteases (e.g. ADAMTS4). Methods. AC was retrieved from the femoral condyles of 8-week-old pigs. Full thickness 6mmØ AC discs were prepared, defects were induced, and explants cultured for up to 28 days. After fixation, sections were stained using Safranin-O and antibodies against Collagen types I & II, LOX, and ADAMTS4. Gene expression analyses were performed using qPCR. We also cultured devitalized samples, either with or without enzymatic treatment to deplete proteoglycans, for 28 days and similarly assessed repair. Results. Safranin-O staining demonstrated successful integration of cartilage defects over a 28-day period. No significant regulation in the expression of Col1a1, Col2a1, LOX or SLPR genes was observed at any time point. Immunofluorescence staining revealed that only ADAMTS4 localized at the injury surface in integrated samples. Interestingly, we also observed successful spontaneous integration of proteoglycan-depleted devitalized tissue. Conclusion. Cartilage integration in our pig cartilage explant model did not appear to be mediated by upregulation of major cartilage ECM components, enzymatic cross-linkers, or SLRPs. However, spontaneous integration of devitalized, proteoglycan-depleted AC, and localised upregulation of ADAMTS4 at the injured surface in successfully integrated samples, suggest that ADAMTS4 may enhances normal repair in injured AC through local aggrecan depletion, therefore enabling spontaneous cross-linking of collagen fibrils. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

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

Osteocondritis dissecans (OCD) is a relatively common cause of knee pain. Ideal treatment is still controversial. Aim of this exhibit is to describe the outcomes of 5 different surgical techniques in a series of 63 patients. 63patients (age 22.5±7.4 years) affected by OCD of the femoral condyle (45 medial and 17 lateral) were treated by either osteochondral autologous transplantation, autologous chondrocyte implantation with bone graft, biomimetic nanostructured osteochondral scaffold (Maioregen) implantation, bone-cartilage paste graft or bone marrow derived cells transplantation “one-step” technique. Patient evaluation included IKDC score, eq-vas score, X-Rays and MRI preoperatively and at follow-up. Global mean IKDC improved from pre-operative 40.1±14.6 to 77.2±21.3 (p<0.0005) at mean 5.3±4.7 years follow-up, while eq-vas improved from 51.7±17.0 to 83.5±18.3(p<0.0005). No influence of age, size of the lesion, length of follow-up and associated surgeries on the result was found. No differences were found between the results obtained with different surgeries except a slight tendency of better improvement in the result following autologous chondrocyte implantation (p<0.01). Control MRI evidenced a satisfactory repair of cartilaginous layer and subchondral bone. The techniques described were effective in providing good clinical and radiographic results in the treatment of OCD and confirmed the validity of autologous chondrocyte implantation over time. Newer techniques such as Maioregen implantation and “one-step” base on different rationales, the first relying on the characteristics of the scaffold and the second on the regenerative potential of mesenchymal cells. Both of them have the advantages to be minimally invasive surgeries and to require a single operation

Chondral injuries of the knee are extremely common and present a unique therapeutic challenge due to the poor intrinsic healing of articular cartilage. These injuries can lead to significant functional impairment. There are several treatment modalities for articular osteochondral defects, one of which is autologous chondrocyte implantation. Our study evaluates the mid to long term functional outcomes in a cohort of 828 patients who have undergone an autologous chondrocyte implantation procedure (either ACI or MACI), identifying retrospectively factors that may influence their outcome. The influence of factors including age, sex, presence of osteoarthritis and size and site of lesion have been assessed individually and with multivariate analysis. All patients were assessed using the Bentley Functional Score, Visual Analogue Score and the Cincinnati Functional Score. Assessment were performed pre-operatively and of their status in 2010. The majority of patients had several interim scores performed at varying intervals. The longest follow-up was 12 years (range 24 to 153 months) with a mean age of 34 years at time of procedure. The mean defect size was 486 mm2 (range 64 to 2075 mm2). The distribution of lesions was 51% Medial Femoral Condyle, 12.5% Lateral Femoral Condyle, 18% Patella (single facet), 5% Patella (Multifacet) and 6% Trochlea. 4% had cartilage transplant to multiple sites. 30% failed following this procedure at a mean time of 72 months. 52% patients stated a marked improvement in their functional outcomes within the first two years. 49% stated an excellent result following their procedure. High failure rate was noted in those with previous cartilage regenerative procedures, transplants occurring on the patella, particularly if involving multifacets. Multiple site cartilage transplantation was also associated with a high failure rate. Autologous chondrocyte implantation is an effective method of decreasing pain and increasing function, however patient selection plays clear role in the success of such procedure

Aims: Tissue engineering is an increasingly popular method of addressing pathological disorders of cartilage. Recent studies have demonstrated the clinical efficacy of autologous chondrocytes implantation in cartilage defects, but there is little information on the use of a solid scaffold and on the composition of the repair tissue. The present study analysed the clinical outcome and the histological characteristics of membrane-seeded autologous chondrocyte implantation at 12–24 month after operation. Materials and methods: Eleven patients (7 males and 4 females, mean age 37 years) suffering from cartilage lesions of the knee (10 cases) and the ankle (1 case), underwent autologous chondrocyte implantation procedure in which the expanded cells were seeded on type I/III collagen membrane before transplantation (MACI – Verigen, D). Clinical outcomes were assessed by ICRS evaluation package: revised IKDC form and Knee Osteoarthritis and Injury Outcome Score (KOOS). At least 12 months after implantation biopsy samples were arthroscopically obtained from 7 patients previous informed consent. The regenerated tissue were taken according to the ICRS standardized procedure. The specimens were stained with safranin-O and alcian blue, polyclonal antibodies anti S-100 protein and monoclonal antibodies anti chondroitin sulphate, anti-collagen type I and II. Moreover the number of cells/area was quantitatively assessed by histomorphometric method (Quantimet 500+). Ultrastructural analysis was also performed by transmission electron microscopy (TEM). The specimens were evaluated by the ICRS visual histological assessment scale. Results: Improvement 12 months after operation was found subjectively (39.7 to 57.9) and in knee function levels. The International Knee Documentation Committee (IKDC) scores showed marked improvement at 12 months (87% A/B). 90% of biopsies showed: smooth articular surface (I:3), hyaline-like matrix cartilage (II:3), cell distribution (columnar-clusters III:2), predominantly viable cells (IV:3), normal subchondral bone (V:3), normal cartilage mineralization and tide-mark (VI:3). All sections were clearly stained with safranin-O and alcian blue. In all the specimens the cells revealed a strong immunoreaction for S-100 protein and showed a positive reaction for chondroitin-S and type II collagen. Type I collagen was immuno-detected in the more superficial layers of the biopsies. TEM analysis revealed a defined chondral cell phenotype within a chondroid matrix. Tissue heterogeneity and irregularities of the surface were observed in two cases. Conclusions: Clinical improvement and hyaline-like appearance of the repair tissue indicate that membrane-seeded autologous chondrocyte implantation is an effective technique for the treatment of cartilage lesions

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

Osteoarthritis (OA) is a progressive and degenerative joint disease resulting in changes to articular cartilage. In focal early OA defects, autologous chondrocyte implantation (ACI) has a 2-fold failure rate due to poor graft integration and presence of inflammatory factors (e.g. Interleukin-1β). Bone marrow derived mesenchymal stem cells (MSCs) are an alternative cell source for cell-based treatments due to their chondrogenic capacity, though in vivo implantation leads to bone formation. In vivo, chondrocytes reside under an oxygen tension between 2–7% oxygen or physioxia. Physioxia enhances MSC chondrogenesis with reduced hypertrophic marker (collagen X and MMP13) expression compared to hyperoxic conditions (20% oxygen). This study sought to understand whether implantation of physioxic preconditioned MSCs improves cartilage regeneration in an early OA defect model compared to hyperoxic MSCs. Bone marrow extracted from New Zealand white rabbits (male: 5–6 months old; n = 6) was split equally for expansion under 2% (physioxia) or 20% (hyperoxia) oxygen. Chondrogenic pellets (2 × 105 cells/pellet) formed at passage 1 were cultured in the presence of TGF-β1 under their expansion conditions and measured for their wet weight and GAG content after 21 days. During bone marrow extraction, a dental drill (2.5mm diameter) was applied to medial femoral condyle on both the right and left knee and left untreated for 6 weeks. Following this period, physioxia and hyperoxia preconditioned MSCs were seeded into a hyaluronic acid (TETEC) hydrogel. Fibrous tissue was scraped and then MSC-hydrogel was injected into the right (hyperoxic MSCs) and left (physioxia MSCs) knee. Additional control rabbits with drilled defects had fibrous tissue scrapped and then left untreated without MSC-hydrogel treatment for the duration of the experiment. Rabbits were sacrificed at 6 (n = 3) and 12 (n = 3) weeks post-treatment, condyles harvested, decalcified in 10% EDTA and sectioned using a cryostat. Region of interest was identified; sections stained with Safranin-O/Fast green and evaluated for cartilage regeneration using the Sellers scoring system by three blinded observers. Physioxic culture of rabbit MSCs showed significantly shorter doubling time and greater cell numbers compared to hyperoxic culture (∗p < 0.05). Furthermore, physioxia enhanced MSC chondrogenesis via significant increases in pellet wet weight and GAG content (∗p < 0.05). Implantation of physioxic preconditioned MSCs showed significantly improved cartilage regeneration (Mean Sellers score = 7 ± 3; ∗p < 0.05) compared to hyperoxic MSCs (Sellers score = 12 ± 2) and empty defects (Sellers score = 17 ± 3). Physioxia enhances in vitro rabbit MSC chondrogenesis. Subsequent in vivo implantation of physioxia preconditioned MSCs improved cartilage regeneration in an early OA defect model compared to hyperoxic MSCs. Future studies will investigate the mechanisms for enhanced in vivo regeneration using physioxia preconditioned MSCs

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 & 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

Introduction: Autologous chondrocyte implantation was introduced in 1994 by Brittberg and Peterson for the treatment of large full-thickness focal chondral defects. The purpose of the present study was to evaluate the mid-term results of this technique in a group of patients with post-traumatic chondral defects of the knee. Materials and Methods: Fifteen patients underwent autologous chondrocyte implantation between 2001 and 2006 and were prospectively assessed preoperatively, at 3, 6, 9, 12 months, 3.5 years and last follow-up with use of standard rating scales (IKDC subjective score, pain Visual Analogic Scale (VAS), Brittberg and Peterson’s score). The inclusion’s criteria were: pain VAS more than 40/100, age between 18 and 50 years, focal chondral defect in weight bearing area grade 3 or 4 and informed and signed consent. Patients with varus or valgus deformities with malalignement more than 5 degrees, knee instabilities and signs of arthritis on radiographs were excluded. The same experienced surgeon performed all the procedures. Results: Fourteen patients were reviewed at the latest follow-up. The mean age of the patients at the time of autologous chondrocyte transplantation was 37.7 years (range, 30 to 45). The mean duration of symptoms was 2.9 years (0.5 to 7). Nine patients (83%) had previous operations on the index knee. The defect was located on the medial femoral condyle in 11 patients and on the lateral femoral condyle in 3. The mean lesion size was 1.80 cm. 2. (range, 1.5 to 3.5 cm. 2. ) after débridement. After a mean duration of follow-up of 6 years (3.3–7.8), 84% of the patients had improvement on a patient self-assessment questionnaire. The IKDC subjective score and Brittberg-Peterson’s score were all improved. The mean IKDC subjective score increased from 40 (27.6–65.5) preoperatively to 60.2 (35.6–89.6) at the latest evaluation. The mean pain VAS decreased from 66.3 (44–89) to 23.2 (0–77). The Brittberg and Peterson’s score decreased from 54.4 (11.8–98.2) to 32.9 (0–83.9). Two patients (16.7%) felt no improvement by the chondrocyte transplantation at the last follow-up. Two complications occurred: graft periosteum hypertrophy treated by débridement and a pulmonary embolus. Discussion: Our results are similar than those reported in the literature. These outcomes are encouraging and need further follow-up to confirm the long-term efficacy of autologous chondrocyte implantation

Articular cartilage defects of the knee occur commonly in sports injuries and trauma. Increasing evidence suggests that the only technique that enables the regeneration of articular hyaline cartilage in chondral defects is autologous chondrocyte implantation (ACI). Here we have reported our clinical experience of autologous chondrocyte implantation using biodegradable type I/III collagen membrane (CACI). A total of 26 patients (age range from 19 to 60 years, average 37 years) was conducted with CACI. Pre-operative magnetic resonance imaging (MRI) scans were performed on all patients. Post-operative MRI scans were planned for approximately three and 12 months after the surgery to determine the success of integration of implanted chondrocytes. The results demonstrated that the initial post-operative MRI scans at three months showed the presence of oedematous tissue at the defect sites in 23 patients, contrasting with the fluid filled defects seen preoperatively and with and MRI signal differing from that of the surrounding normal hyaline articular cartilage. MRI scans in nine patients at 12 months after their operations showed maturation of cartilage graft in all patients. Apopototic testing of the chondrocytes using Annexin IV before implantation showed that the viability of the chondrocytes was over 85% where the apopototic rate of chondrocytes was less than 2%. One patient with an apopototic rate of over 10% has a delayed repair in cartilage defects as shown by MRI. In conclusion, early phase clinical studies showed that autologous chondrocyte implantation remains promising for the treatment of chondral defects with restoration of hyaline cartilage. Longer clinical follow-up of the patients and better assessment of cellular phenotype of chondrocytes before implantation are required

The December 2012 Shoulder & Elbow Roundup. 360. looks at: whether allograft is biomechanically superior in large Hill-Sachs defects; glenoid bone loss in shoulder dislocators; repairing irreparable cuff tears; acromioclavicular joint injuries; whether more radiographs equals more surgery; whether reverse TSR is cheaper than hemiarthroplasty; autologous chondrocyte implantation in the shoulder; and fracture of the clavicle