Autologous Chondrocyte Implantation Graft Research Articles

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

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

Prior Bone Marrow Stimulation Surgery Influences Outcomes After Cell-Based Cartilage Restoration: A Systematic Review and Meta-analysis.

Background:Cell-based cartilage restoration with autologous chondrocyte implantation (ACI) is a safe and effective treatment for symptomatic cartilage lesions. Many patients undergoing ACI have a history of prior surgery, including bone marrow stimulation (BMS). There is mounting evidence that a history of prior BMS may impede healing of the ACI graft.Purpose/Hypothesis:The purpose of this study was to compare the failure rates of primary ACI with ACI after prior BMS. We hypothesized that ACI after BMS would have a significantly higher failure rate (defined as reoperation, conversion to arthroplasty, and/or imaging-based failure) compared with primary ACI.Study Design:Systematic review; Level of evidence, 4.Methods:A literature search was performed by use of PubMed and Embase databases for relevant articles published through October 2, 2020, to identify studies evaluating outcomes and failures rates of ACI after prior BMS in the knee.Results:Included were 11 studies comprising 1479 ACI procedures. The mean age at surgery ranged from 18.3 to 39.1 years, and the mean follow-up ranged from 3 to 20.6 years. All studies reported failure rates. The overall failure rate was significantly higher in the patients who underwent ACI after BMS, at 26.4% compared with 14.8% in the ACI group (P < .001). Meta-analysis demonstrated an increased risk of failure in patients with a history of prior BMS (log odds ratio = –0.90 [95% confidence interval, –1.38 to –0.42]).Conclusion:This systematic review demonstrated that failure rates were significantly higher for patients treated with ACI after BMS relative to patients undergoing ACI without prior BMS. This finding has important implications when considering the use of BMS for defects that are amenable to cell-based restoration and when determining treatment options after failed BMS.Registration:PROSPERO (CRD42020180387).

Typical MRI‑pattern suggests peak maturation of the ACI graft 2 years after third‑generation ACI: a systematic review

Objectives:The purpose of the present article was (1) to systematically review the current literature and (2) to collect data regarding the postoperative magnetic resonance imaging (MRI) appearance of third-generation autologous chondrocyte implantation (ACI) grafts and (3) to provide an overview of imaging findings at various postoperative time points.Methods:A systematic review of the literature in Medline (Pubmed) and Embase was performed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Articles which reported the post-operative MRI morphological outcomes following the use of third-generation ACI for treatment of knee cartilage lesions were included. All MRI results were allocated to six different time intervals: ≤ 3 months, > 3–6 months, > 6 months–1 year, > 1 year–2 years, > 2–5 years and > 5 years after surgery.Results:A total of 22 studies were included and the study populations ranged from 13 to 180 patients adding up to a total of 951 patients. Parameters such as defect fill, border integration, surface contour, graft morphology and integrity of the subchondral lamina all improve gradually with a peak two years following surgery suggesting complete graft maturation at this time point. After this peak, a statistically insignificant decline is noted for most of the parameters. Signal intensity was found to gradually shift from hyperintense to isointense in the first 36 months and to hypointense later on. Contrarily, subchondral bone edema is not only a postoperative feature of the procedure but also can reappear or persist up to ten years after surgery. As graft failures can appear after two years, consequently, the MRI composite score is also affected.Conclusion:Recurring patterns in postoperative MRI appearance were observed in certain parameters including defect filling, graft signal intensity and structure, border integration of the graft while parameters like subchondral bone tend to be unpredictable. Given the heterogenous findings in terms of clinical correlation, and relating that aspect to the patterns found in this review, an MRI is justified at three months, one year, two years and five years after surgery, unless the clinical symptomatology and individual patient needs dictate otherwise.

Typical MRI-pattern suggests peak maturation of the ACI graft 2years after third-generation ACI: a systematic review.

The purpose of the present article was (1) to systematically review the current literature and (2) to collect data regarding the postoperative magnetic resonance imaging (MRI) appearance of third-generation autologous chondrocyte implantation (ACI) grafts and (3) to provide an overview of imaging findings at various postoperative time points. A systematic review of the literature in Medline (Pubmed) and Embase was performed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Articles which reported the post-operative MRI morphological outcomes following the use of third-generation ACI for treatment of knee cartilage lesions were included. All MRI results were allocated to six different time intervals: ≤ 3months, > 3-6months, > 6months-1year, > 1year-2years, > 2-5years and > 5years after surgery. A total of 22 studies were included and the study populations ranged from 13 to 180 patients adding up to a total of 951 patients. Parameters such as defect fill, border integration, surface contour, graft morphology and integrity of the subchondral lamina all improve gradually with a peak two years following surgery suggesting complete graft maturation at this time point. After this peak, a statistically insignificant decline is noted for most of the parameters. Signal intensity was found to gradually shift from hyperintense to isointense in the first 36months and to hypointense later on. Contrarily, subchondral bone edema is not only a postoperative feature of the procedure but also can reappear or persist up to ten years after surgery. As graft failures can appear after two years, consequently, the MRI composite score is also affected. Recurring patterns in postoperative MRI appearance were observed in certain parameters including defect filling, graft signal intensity and structure, border integration of the graft while parameters like subchondral bone tend to be unpredictable. Given the heterogenous findings in terms of clinical correlation, and relating that aspect to the patterns found in this review, an MRI is justified at three months, one year, two years and five years after surgery, unless the clinical symptomatology and individual patient needs dictate otherwise. IV.

The Effect of Mechanical Leg Alignment on Cartilage Restoration With and Without Concomitant High Tibial Osteotomy

To assess graft survivorship in patients who underwent autologous chondrocyte implantation (ACI) or osteochondral allograft transplantation (OCA) for the treatment of focal full-thickness cartilage lesions on the medial femoral condyle with and without concomitant high tibial osteotomy (HTO), depending on the preoperative lower-extremity alignment. A secondary purpose was to retrospectively evaluate associated factors for ACI and OCA graft failures. A total of 168 patients who underwent cartilage repair with ACI or OCA with or without HTO for focal chondral defects on the medial femoral condyle by a single surgeon between March 2007 and February 2018 were included. Clinical notes, operative reports, and radiographic imaging were reviewed for each patient. Detailed Kaplan-Meier analyses were performed based on patient's mechanical axis alignment. In a subanalysis, failures and nonfailures in patients treated with ACI or OCA were comparatively evaluated. In ACI, neutral mechanical alignment resulted in a significantly longer graft survival compared with slight valgus alignment (P= .003 and P= .05, respectively). No significant differences in survivorship were seen based on mechanical axis alignment in OCA patients (P > .05). Patients who were considered failures after ACI presented significantly more often with valgus alignment (P= .002), whereas failures in the OCA group were more often female and smokers (P= .025; P= .034). In summary, the results of this study suggest that neutral mechanical axis alignment, regardless if physiologic or through HTO, improves survivorship in patients undergoing medial compartment ACI. Neutral alignment also showed a trend towards improved survivorship in patients after OCA, but this did not reach statistical significance. Case-Series; Level of evidence,4.

The Role of Hypertension in Cartilage Restoration: Increased Failure Rate After Autologous Chondrocyte Implantation but Not After Osteochondral Allograft Transplantation.

Objectives. The purpose of this study was to examine whether patients with diagnosed hypertension have an increased risk of graft failure following cartilage repair with either autologous chondrocyte implantation (ACI) or osteochondral allograft transplantation (OCA). We hypothesized that hypertension is related to higher ACI and OCA graft failure. Design. Patients who underwent ACI or OCA transplantation between February 2009 and December 2016 were included in this study. Inclusion criteria were (1) at least 2 years' follow-up, (2) available information related to the living habits (smoking and medication status), and (3) available information related to the presence of hypertension, diabetes mellitus, or hyperlipidemia. To identify potential independent risk factors of graft failure, univariate screening was performed and factors with significance at a level of P < 0.1 were entered in multivariate logistic regression models. Results. A total of 368 patients (209 ACI and 159 OCA) were included into our study. In the ACI group, 61 patients' (29.1%) graft failed. Univariate screening identified older age, female gender, defect size, higher prevalence of hypertension, and smoking as a predictor of graft failure. Following, multivariate logistic regression revealed female gender (odds ratio [OR] 1.02, P = 0.048), defect size (OR 1.07, P = 0.035), and hypertension (OR 3.73, P = 0.023) as significant independent risk factors predicting graft failure after ACI. In the OCA group, 29 patients' (18.2%) graft failed and none of the included factors demonstrated to be a potential risk factor for graft failure. Conclusion. Hypertension, defect size, and female gender seem to predict ACI graft failure but not OCA failure.

Survival Analysis of Revision Autologous Chondrocyte Implantation for Failed ACI

Background: Autologous chondrocyte implantation (ACI) provides a successful outcome for treating articular cartilage lesions. However, there have been very few reports on the clinical outcomes of revision ACI for failed ACI. Purpose: To evaluate clinical outcomes in patients who underwent revision ACI of the knee for failure of an initial ACI and to determine the factors affecting the survival rate. Study Design: Case series; Level of evidence, 4. Methods: A review of a prospectively collected data set was performed from patients who underwent revision ACI of the knee for failure of an initial ACI between 1995 and 2014 by a single surgeon. The authors evaluated 53 patients (53 knees; mean age, 38 years) over a mean 11.2-year follow-up (range, 2-20). A total of 62 cartilage lesions were treated for failed graft lesions after an initial ACI, and 31 new cartilage lesions were treated at revision ACI, as there was progression of disease. Overall, 93 cartilage lesions (mean, 1.8 lesions per knee) with a total surface area of 7.4 cm2 (range, 2.5-18 cm2) per knee were treated at revision ACI. Survival analysis was performed with the Kaplan-Meier method, with ACI graft failure or conversion to a prosthetic arthroplasty as the endpoint. The modified Cincinnati Knee Rating Scale, Western Ontario and McMaster Universities Osteoarthritis Index, visual analog scale, and 36-Item Short Form Health Survey were used to evaluate clinical outcomes. Patients also self-reported knee function and satisfaction. Standard radiographs were evaluated with Kellgren-Lawrence grades. Results: Survival rates were 71% and 53% at 5 and 10 years, respectively. Survival subanalysis revealed a trend that patients without previous cartilage repair procedures before an initial ACI had better survival rates than those with such procedures (81% vs 62% at 5 years, 64% vs 42% at 10 years, P = .0958). Patients with retained grafts showed significant improvement in pain and function, with a high level of satisfaction. At a mean 5.1 years postoperatively, 18 of 27 successful knees were radiographically assessed with no significant osteoarthritis progression. Outcomes for 26 patients were considered failures (mean, 4.9 years postoperatively), in which 15 patients had prosthetic arthroplasty (mean, 4.6 years) and the other 11 patients had revision cartilage repair (mean, 5.4 years) and thus could maintain their native knees. Conclusion: Results of revision ACI for patients who failed ACI showed acceptable clinical outcomes. Revision ACI may be an option for young patients after failed initial ACI, particularly patients without previous cartilage repair procedures and those who desire to maintain their native knees.

Survival Rates of Various Autologous Chondrocyte Grafts and Concomitant Procedures. A Prospective Single-Center Study over 18 Years

Seven different autologous chondrocyte implantation (ACI) grafts were used consecutively over a period of 18 years for the treatment of cartilage lesions in the knees. The aim was to evaluate this entire ACI patient series for graft-related or unrelated serious adverse events (SAE), graft failures, and to reveal potential risk factors for these incidents. The study group comprised 151 operated patients: classical periosteum-ACI (n = 45); ACI-seeded fibrin-collagen patch, fixed by either periosteum (n = 59), collagen membrane (n = 15), or fibrin glue (n = 6); ACI seeded alginate-agarose hydrogel (n = 14); and biomimetic collagen-hydroxyapatite scaffold injected with the ACI suspension (n = 12). The covariates analyzed as possible predicting factors were: age, gender, BMI, lesion depth, lesion size, lesion location, previous surgeries, and concomitant procedures. The Kaplan–Meier method for estimating survival curves, and Cox’s proportional hazards model to test for covariates, were used in the statistical analysis. The patients in this series, follow-up 10.1 (2.1–18.3) years, encountered 11% of graft-related SAE (risk factors: previous cartilage surgery, age over 40 years, BMI over 25 kg/m2, and meniscus surgery) and 10% of graft unrelated SAE (risk factors: meniscus surgery and osteotomy). None of these factors was a risk for definitive graft failure. The 10-year graft survival rate was 86%. Females had 2.8 times higher incidence of graft failures than males. There was a tendency toward higher graft failures after a previous cartilage surgery. Different ACI graft types offered safe and durable cartilage repair. Female gender, age over 40 years, increased weight, previous cartilage surgery, and meniscus loss showed increased risk for revision surgery or graft failures.

Severe Bone Marrow Edema Among Patients Who Underwent Prior Marrow Stimulation Technique Is a Significant Predictor of Graft Failure After Autologous Chondrocyte Implantation

Background: Autologous chondrocyte implantation (ACI) is a well-established cartilage repair procedure; however, numerous studies have shown higher ACI graft failure rates after prior marrow stimulation techniques (MSTs). Purpose: To identify which factors may predict decreased graft survival after ACI among patients who underwent a prior MST. A secondary aim was to investigate the specificity of these predictors. Study Design: Case-control study; Level of evidence, 3. Methods: In this review of prospectively collected data, the authors analyzed 38 patients who had failed prior MST surgery and subsequently underwent collagen-covered ACI (case group). The case group was divided into graft failure ACI (n = 8, 21%) and successful ACI (n = 30, 79%). Fourteen clinical variables were categorized and analyzed to determine predictors for failure of the ACI graft: age, body mass index, sex, defect characteristics (number, size, location, etiology, type), presence of kissing lesion, intraoperative presence of intralesional osteophyte, time between an MST and ACI, previous surgery, duration of the symptoms, and concomitant surgical procedure. Preoperative magnetic resonance imaging (MRI) was used to evaluate the severity of subchondral bone marrow edema (BME), graded I (absent) to IV (severe), and the presence of subchondral cyst, hypertrophic sclerosis, and intralesional osteophyte. The effects of these MRI findings on the graft survivor were also investigated. Concurrently, a control group without a prior MST was matched to investigate the specificity of the previously determined predictors. These patients were matched individually according to age, sex, body mass index, and outcome of the procedure (failure [n = 8] or successful [n = 30] per the case group). Results: In the case group, the presence of preoperative severe BME was significantly higher among patients with failed ACI as compared with patients with successful ACI (P < .001). In the control group, the presence of severe BME was not significantly different between the failure and successful groups (P = .747). The ACI graft failure rate among patients with a prior MST and preoperative grade IV BME was 83.7% at 5 years postoperatively, resulting in a significantly lower survival rate as compared with patients with a prior MST and without severe BME (5-year graft failure rate, 6.5%; P < .001). All the other parameters did not differ significantly. Conclusion: After a prior MST, the presence of grade IV BME by MRI was a predictive factor for graft failure among patients who then underwent second-generation ACI.

Graft Hypertrophy After Third-Generation Autologous Chondrocyte Implantation Has No Correlation With Reduced Cartilage Quality: Matched-Pair Analysis Using T2-Weighted Mapping

Background: Graft hypertrophy is common after matrix-based autologous chondrocyte implantation (ACI) in the knee joint. However, it is not clear whether graft hypertrophy is a complication or an adjustment reaction in the cartilage regeneration after ACI. Purpose: To analyze the cartilage quality of the ACI regeneration with graft hypertrophy using T2-weighted mapping. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 91 patients with isolated cartilage defects (International Cartilage Repair Society [ICRS] grade III-IV) of the knee were treated with Novocart 3D, a third-generation, matrix-based, ACI procedure in the knee joint. All patients were evaluated with a standardized magnetic resonance imaging protocol after 3, 6, 12, 24, 36, and 48 months postoperatively. For morphological and biochemical assessment, the T2-weighted relaxation times of the ACI grafts as well as the healthy surrounding cartilage were determined. The results of the 20 patients with graft hypertrophy (hypertrophic group) were compared with the results of 21 matched patients without graft hypertrophy (nonhypertrophic group) after ACI. Match-paired analysis was performed by comparison of age, defect size, and body mass index. Results: The T2-weighted relaxation times of the ACI graft showed significant improvement, with values decreasing from 52.1 milliseconds to 33.3 milliseconds after 48 months. After 12 months, the T2-weighted relaxation times were constant and comparable with the healthy surrounding cartilage. Graft hypertrophy was seen in 22% (n = 20) of the patients who underwent ACI. A significant difference in T2-weighted relaxation times between the hypertrophic and nonhypertrophic ACI grafts could not be found except after 36 months (hypertrophic T2-weighted relaxation time/nonhypertrophic T2-weighted relaxation time: 3 months, 48.0/56.4 ms, P = .666; 6 months, 45.6/42.5 ms, P = .280; 12 months, 39.3/34.7 ms, P = .850; 24 months, 34.8/32.2 ms, P = .742; 36 months, 34.6/38.2 ms, P = .030; 48 months, 34.2/32.3 ms, P = .693). Conclusion: The T2-weighted relaxation time of the ACI graft cartilage showed significant improvements over the observation period of 4 years postoperatively. After 2 years, graft maturation was completed. Graft hypertrophy after ACI was seen in 22% of the patients. Reduced cartilage quality could not be found in patients with graft hypertrophy after ACI.

Chondrogenic potential of IL-10 in mechanically injured cartilage and cellularized collagen ACI grafts.

The application of adjunctive mediators in Autologous chondrocyte implantation (ACI) techniques might be useful for improving the dedifferentiated chondrocyte phenotype, to support neocartilage formation and inhibit post-traumatic cartilage destruction. In this study we examined if (a) interleukin 10 treatment can cause chondrogenic phenotype stabilization and matrix preservation in mechanically injured cartilage and if (b) IL-10 can promote chondrogenesis in a clinically applied collagen scaffold for ACI treatment. For (a) bovine articular cartilage was harvested, subjected to an axial unconfined injury and treated with bovine IL-10 (1-10,000pg/ng/ml). For (b) a post-operatively remaining ACI graft was treated with human IL-10. Expression levels of type I/II/X collagen, SOX9 and aggrecan were measured by qPCR (a,b). After 3 weeks cell death was analyzed (nuclear blebbing and TUNEL assay) and matrix composition was determined by GAG measurements and immunohistochemistry (aggrecan, type I/II collagen, hyaluronic acid). One way ANOVA analysis with Bonferroni's correction. (a) IL-10 stabilized the chondrogenic phenotype after injurious compression and preserved matrix integrity. This was indicated by elevated expression of chondrogenic markers COL2A1, ACAN, SOX9, while COL1A1 and COL10A1 were reduced. An increased GAG content paralleled this and histological staining of type 2 collagen, aggrecan and toluidine blue were enhanced after 3 weeks. (b) IL-10 [100pg/ml] improved the chondrogenic differentiation of human chondrocytes, which was accompanied by cartilaginous matrix formation after 3 weeks of incubation. Interleukin-10 is a versatile adjuvant candidate to control the post-injurious environment in cartilage defects and promote chondrogenesis in ACI grafts.

Intermediate- to Long-Term Results of Combined Anterior Cruciate Ligament Reconstruction and Autologous Chondrocyte Implantation.

Background:Cartilage injury associated with anterior cruciate ligament (ACL) ruptures is common; however, relatively few reports exist on concurrent cartilage repair with ACL reconstruction. Autologous chondrocyte implantation (ACI) has been utilized successfully for treatment of moderate to large chondral defects.Hypothesis:ACL insufficiency with relatively large chondral defects may be effectively managed with concurrent ACL reconstruction and ACI.Study Design:Case series; Level of evidence, 4.Methods:Patients undergoing concurrent ACL primary or revision reconstruction with ACI of single or multiple cartilage defects were prospectively evaluated for a minimum 2 years. Pre- and postoperative outcome measures included the modified Cincinnati Rating Scale (MCRS), Western Ontario and McMaster Universities Osteoarthritis Index, visual analog pain scales, and postsurgery satisfaction surveys. ACI graft failure or persistent pain without functional improvement were considered treatment failures.Results:Twenty-six patients were included, with 13 primary and 13 revision ACL reconstructions performed. Mean defect total surface area was 8.4 cm2, with a mean follow-up of 95 months (range, 24-240 months). MCRS improved from 3.62 ± 1.42 to 5.54 ± 2.32, Western Ontario and McMaster Universities Osteoarthritis Index from 45.31 ± 17.27 to 26.54 ± 17.71, and visual analog pain scale from 6.19 ± 1.27 to 3.65 ± 1.77 (all Ps <.001). Eight patients were clinical failures, 69% of patients were improved at final follow-up, and 92% stated they would likely undergo the procedure again. No outcome correlation was found with regard to age, body mass index, sex, defect size/number, follow-up time, or primary versus revision ACL reconstruction. In subanalysis, revision ACL reconstructions had worse preoperative MCRS scores and greater defect surface areas. However, revision MCRS score improvements were greater, resulting in similar final functional scores when compared with primary reconstructions.Conclusion:Challenging cases of ACL tears with large chondral defects treated with concurrent ACL reconstruction and ACI can lead to moderately improved pain and function at long-term follow-up. Factors associated with clinical failure are not clear. When combined with ACI, patients undergoing revision ACL reconstructions have worse function preoperatively compared with those undergoing primary reconstructions but have similar final outcomes.

Graft Maturation of Autologous Chondrocyte Implantation

Background: Autologous chondrocyte implantation (ACI) using tissue-engineered cartilage is a successful therapy for full-thickness cartilage lesions in the knee joint. However, in vivo graft maturation is still unclear. Purpose: The aim of this prospective study was to analyze graft maturation after ACI in the knee using objective T2 mapping in correlation with the clinical outcomes within a 3-year postoperative course. Study Design: Case series; Level of evidence, 4. Methods: A total of 13 patients with isolated cartilage defects of the knee were treated with Novocart 3D, a matrix-based ACI procedure in the knee joint. The patients had complete data from International Knee Documentation Committee (IKDC) scores and MRI examinations for 6 to 36 months postoperatively. All cartilage defects were arthroscopically classified as Outerbridge grades III and IV. The mean area of the cartilage defect was 5.6 cm2. Postoperative clinical and MRI examinations were conducted at 6, 12, 24, and 36 months after surgery. The modified magnetic resonance observation of cartilage repair tissue (MOCART) score was used to evaluate the quality and integration of the Novocart 3D implants on MRI. The T2 relaxation time values of the ACI graft and healthy native cartilage areas were determined to assess graft maturation using T2 mapping. Results: The T2 relaxation times of the ACI graft showed significant improvement, with decreasing values from 41.6 milliseconds at 6-month follow-up to 32.4 and 30.9 milliseconds after 24 and 36 months, respectively. These values were similar to the T2 relaxation times of the native surrounding cartilage. There was no correlation between the clinical outcomes (IKDC score) and T2 relaxation time values. Conclusion: The T2 relaxation time in the repaired tissue showed similar values compared with normal hyaline cartilage. Graft maturation after ACI in the knee joint needs at least 1 year, with ongoing adjustment of the T2 relaxation time values compared with native surrounding cartilage. A correlation between increasing ACI graft maturation and clinical outcomes (IKDC score) could not be found with the data available.

The John Insall Award: A Minimum 10-year Outcome Study of Autologous Chondrocyte Implantation

Autologous chondrocyte implantation (ACI) has demonstrated good and excellent results in over 75% of patients up to 10 years after surgery. Reports of longer-term outcomes, however, remain limited. The purposes of this study were to describe the (1) survivorship of ACI grafts; (2) the long-term functional outcomes using validated scoring tools after ACI; and (3) to provide an analysis of potential predictors for failure. Two hundred ten patients treated with ACI were followed for more than 10 years. Indications for the procedure included symptomatic cartilage defects in all compartments of the knee unresponsive to nonoperative measures. Mean age at surgery was 36 ± 9 years; mean defect size measured 8.4 ± 5.5 cm(2). Outcome scores were prospectively collected pre- and postoperatively at the last followup. At a mean of 12 ± 2 years followup, 53 of 210 patients (25%) had at least one failed ACI graft. Nineteen of these patients went on to arthroplasty, 27 patients were salvaged with revision cartilage repair, and seven patients declined further treatment; three patients were lost to followup. The modified Cincinnati increased from 3.9 ± 1.5 to 6.4 ± 1.5, WOMAC improved from 39 ± 21 to 23 ± 16, Knee Society Score (KSS) knee score rose from 54 ± 18 to 79 ± 19, and KSS function from 65 ± 23 to 78 ± 17 (all p < 0.0001). The Physical Component of the SF-36 score increased from 33 ± 14 to 49 ± 18, whereas the Mental Component improved from 46 ± 14 to 52 ± 15 (both p < 0.001). Survivorship was higher in patients with complex versus salvage-type lesions (p = 0.03) with primary ACI versus ACI after prior marrow stimulation (p = 0.004) and with concomitant high tibial osteotomy (HTO) versus no HTO (p = 0.01). ACI provided durable outcomes with a survivorship of 71% at 10 years and improved function in 75% of patients with symptomatic cartilage defects of the knee at a minimum of 10 years after surgery. A history of prior marrow stimulation as well as the treatment of very large defects was associated with an increased risk of failure.

Combined autologous chondrocyte implantation (ACI) with supra-condylar femoral varus osteotomy, following lateral growth-plate damage in an adolescent knee: 8-year follow-up

We report the 8-year clinical and radiographic outcome of an adolescent patient with a large osteochondral defect of the lateral femoral condyle, and ipsilateral genu valgum secondary to an epiphyseal injury, managed with autologous chondrocyte implantation (ACI) and supracondylar re-alignment femoral osteotomy. Long-term clinical success was achieved using this method, illustrating the effective use of re-alignment osteotomy in correcting mal-alignment of the knee, protecting the ACI graft site and providing the optimum environment for cartilage repair and regeneration. This is the first report of the combined use of ACI and femoral osteotomy for such a case.

Concomitant Autologous Chondrocyte Implantation with Osteochondral Grafting for Treatment of a Massive Osteochondral Defect in the Bilateral Knees of a Child

We report the case of a 15-year-old patient who underwent concomitant autologous chondrocyte implantation and osteochondral grafting for the treatment of a massive osteochondritis dissecans defect in the left knee and autologous chondrocyte implantation in the right knee joint. Magnetic resonance imaging showed large osteochondral defects in both the knee joints measuring 8-9 cm(2). Both defects were located in the weight-bearing areas of the medial femoral condyles. Therefore, simultaneous autologous chondrocyte implantation (ACI) and osteochondral autograft transplantation (OAT) for the left knee defect and ACI for the right knee joint were performed. Osteochondral plugs were harvested from the patellofemoral joint of the same left knee and grafted into the most dorsal regions of the large osteochondral defect of the left knee. The remaining osteochondral defect was covered with ACI using collagen type I and III membrane and chondrocyte cells. The membrane was implanted into more proximal part of the osteochondral defect of the left knee. Time interval between operations of the left and right knee joints was 6 months. Magnetic resonance imaging at 6 months after each knee surgery showed good preservation of the OAT and ACI grafts. The most recent follow-up examination, performed 12 months after surgeries, has shown excellent results with an International Knee Documentation Committee score of 95.59±4.64 and 96.88±4.69 for the right and left knee joints, respectively, and full range of knee motions with no symptoms. In this clinical case, the combination of ACI and OAT methods in a one-step procedure produced a good reconstruction of the joint surface with excellent clinical outcomes in the both knee joints of the same patient. Autologous osteochondral grafting and autologous chondrocyte implantation can be combined for the treatment of large osteochondral defects of the knee.

Autologous Chondrocyte Implantation: Natural History of Postimplantation Periosteal Hypertrophy and Effects of Repair-Site Debridement on Outcome

Our purposes were to report the clinical outcome of autologous chondrocyte implantation (ACI) patients with graft hypertrophy compared with that of unoperated ACI patients and to longitudinally assess the effects of graft hypertrophy debridement. We divided 170 knee ACI patients with a minimum of 2 years' follow-up into groups according to the need for reoperation after ACI and the findings at surgery. Group A (n = 73) comprised patients who did not undergo reoperation, group B (n = 61) comprised patients who underwent reoperation and had findings unrelated to the repair, and group C (n = 36) comprised patients who underwent reoperation and had isolated graft hypertrophy. The International Knee Documentation Committee, modified Cincinnati knee rating, and Short Form 36 physical component scores for the 3 groups were compared. Of the repairs debrided because of graft hypertrophy, 41 were longitudinally assessed with arthroscopy or magnetic resonance imaging. The mean follow-up was 42.2 months. Patch-related problems were seen in 73.7% of cases undergoing reoperation less than 2 years after implantation, whereas cartilage-related problems were the dominant finding more than 2 years after implantation (70.2%). Group A patients fared significantly better than group B or C patients with regard to all 3 parameters measured, with no difference between groups B and C. Longitudinal assessment of 41 hypertrophied repairs revealed 18 with signs of pathology after graft debridement. This study shows that reoperation is frequent after ACI and is associated with a less satisfying outcome. Furthermore, debridement of a hypertrophied ACI graft appears to be detrimental as shown by longitudinal assessment of repairs. Level IV, therapeutic case series.

Autologous Chondrocyte Implantation in Knee Joint: MR Imaging and Histologic Features at 1-year Follow-up

To evaluate magnetic resonance (MR) imaging features of autologous chondrocyte implantation (ACI) grafts and compare these with graft histologic features 1 year after ACI for treatment of femoral condylar defects. This study was approved by the regional ethics committee, and all patients gave informed consent. Forty-one patients (mean age, 35 years; 30 men, 11 women) underwent ACI for treatment of femoral condylar defects. One year later, knee joint MR imaging and graft biopsy were performed. Graft biopsy results were categorized into those showing hyaline, mixed fibrohyaline cartilage, fibrocartilage, and fibrous tissue. Standard T1-, T2-, T2*-, and intermediate-weighted sequences were performed, as well as three-dimensional (3D) fast low-angle shot (FLASH) and double-echo steady-state sequences for cartilage assessment. ACI grafts were assessed for signal intensity (with FLASH sequence), thickness, overgrowth, surface smoothness, integration to adjacent cartilage and underlying bone, bone marrow edema underneath graft, and contour of bone underneath graft. MR images were assessed by two observers, first independently and then in consensus. MR imaging findings were correlated with histologic findings. All 41 grafts were present at 1-year follow-up. The graft consisted of hyaline cartilage in four, mixed fibrohyaline cartilage in 10, fibrocartilage in 25, and fibrous tissue in two cases. Graft signal intensity was virtually always lower than adjacent normal cartilage signal intensity, and there was no relationship between graft signal intensity and histologic appearance (P = .34). Graft thickness (P = .83), overgrowth (P = .69), surface smoothness (P = .28), and integration with adjacent cartilage and underlying bone (P = .90); edema in bone marrow underneath graft (P = .63); and bone contour underneath graft (P = .94) at MR imaging had no correlation with graft histologic appearance. Graft overgrowth (n = 16; 39%) and edema-like signal in bone marrow underneath graft (n = 23; 56%) were common. The origin of graft overgrowth remains unclear. With the methods presented here, MR imaging findings cannot predict ACI graft histologic features, and graft histologic appearance determined at biopsy was not related to graft signal intensity, graft thickness, overgrowth, surface smoothness, integration with adjacent cartilage or underlying bone, signal intensity change in underlying bone marrow, or underlying bone contour. Overgrowth and bone marrow changes underneath the graft were common.