Third-generation Autologous Chondrocyte Implantation Research Articles

Increased risk of reoperation and failure to attain clinically relevant improvement following autologous chondrocyte implantation of the knee in female patients and individuals with previous surgeries: a time-to-event analysis based on the German cartilage registry (KnorpelRegister DGOU)

PurposeThis study aimed to analyze the risk of reoperation following autologous chondrocyte implantation (ACI) of the knee utilizing third-generation ACI products in a time-to-event analysis and report on the associated patient-reported outcome measures (PROM) in case of reoperation.MethodsPatients undergoing ACI were included from a longitudinal database. Patient age, sex, body mass index (BMI), number of previous surgeries, lesion localization, lesion size, symptom duration, as well as time and type of reoperation was extracted. A cox proportional-hazards model was applied to investigate the influence of baseline variables on risk of reoperation. Reoperation was defined as any type of subsequent ipsilateral knee surgery, excluding hardware removal. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was utilized to compare PROM between patients with and without reoperation.ResultsA total of 2039 patients were included with 1359 (66.7%) having a minimum follow-up of 24 months. There were overall 243 reoperations (prevalence 17.9%). Minor arthroscopic procedures (n = 96, 39.5%) and revision cartilage repair procedures (n = 78, 32.1%) were the most common reoperations. Nineteen patients (0.9%) reported conversion arthroplasty at 17.7 (10.4) months after ACI. Female sex (HR 1.5, 95% CI [1.2, 2.0], p = 0.002) and the presence of 1–2 previous surgeries (HR 1.5, 95% CI [1.1, 2.0], p = 0.010), or more than 2 previous surgeries (HR 1.9, 95% CI [1.2, 2.9], p = 0.004) were significantly associated with increased risk of reoperation following ACI. Significantly less patients surpassed the minimal clinically important difference (MCID) in the reoperation group at 24 months regarding the KOOS subscores pain (OR 1.6, 95% CI [1.1, 2.2]), quality of life (OR 2.2, 95% CI [1.6, 3.2]), symptoms (OR 2.0 [1.4, 2.9]), and sports (OR 2.0 [1.4, 2.8]).ConclusionFemale patients and individuals with a history of previous surgeries face an elevated risk of requiring reoperation after undergoing ACI, which is associated with failure to attain clinically relevant improvements. A thorough evaluation of the indications for ACI is paramount, particularly when patients have a history of previous surgeries.Level of evidenceLevel III.

Long-term Assessment of Subchondral Bone Changes and Intralesional Bony Overgrowth After Third-Generation Autologous Chondrocyte Implantation: A Retrospective Study

Background: There is an increasing interest in subchondral bone changes and intralesional bony overgrowth (ILBO) after cartilage repair. Their clinical and predictive relevance is unclear and debated. Purpose: To evaluate the long-term development of ILBO and bone marrow edema–like signals (BMELSs) after autologous chondrocyte implantation (ACI) treatment of cartilage defects to find any predictive factors for their appearance. Study Design: Case series; Level of evidence, 4. Methods: A total of 130 patients with 160 cartilage defects in the knee joint treated with third-generation ACI were included in this study. Radiological scores as the MOCART (magnetic resonance observation of cartilage repair tissue), the MOCART 2.0 and the 3D-MOCART using magnetic resonance imaging (MRI), and patient-reported outcome measures such as the Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) score, Noyes Sports Activity Rating Scale (NSARS) score, and Tegner Activity Scale (TAS) score were evaluated between 60 and 120 months (mean, 88 months) postoperatively. The radiological evaluation focused on the occurrence and size of subchondral bone changes, BMELSs, and ILBO during short-, medium-, and long-term follow-up. Results: In long-term evaluation of clinical data, the IKDC score increased preoperatively from 36 to 64, the overall KOOS from 43 to 64, the NSARS score from 30 to 67, and the TAS score from 2 to 3.7. The mean MOCART score was 73; the MOCART 2.0, 69; and the 3D-MOCART, 69 and 70. The authors observed ILBO in 77% and BMELSs in 74% of patients after 60 to 120 months. Previous cartilage surgeries and osteochondral defect buildup showed higher rates of these abnormalities. Early lesions of the subchondral lamina did not predict ILBO in long-term follow-up, but BMELSs predicted later appearance with decreasing size. Conclusion: Subchondral changes frequently appeared in long-term MRI evaluation of patients after ACI. BMELSs showed a decreasing diameter over the years, while the size of ILBO increased in the later follow-ups. These findings did not affect the clinical outcome in the study population. However, osteoarthritis is likely to progress. The degenerative effect and influence on longer-term outcomes needs to be clarified in future studies.

What's New in Sports Medicine.

What's New in Sports Medicine.

A phase I/IIa clinical trial of third-generation autologous chondrocyte implantation (IK-01) for focal cartilage injury of the knee

Background/objectiveThe purpose of this study was to report the outcomes of a clinical trial conducted in Japan to assess the safety and effectiveness of third-generation autologous chondrocyte implantation (ACI) using IK-01 (CaReS™), which does not require flap coverage, in the treatment of patients with focal cartilage injury of the knee. MethodsThis was an open label, exploratory clinical trial. Patients were enrolled between June 2012 and September 2016. The primary endpoint of the study was the International Knee Documentation Committee (IKDC) score at 52 weeks after implantation. The IKDC, Lysholm, and visual analog scale (VAS) scores were evaluated at the time of screening and at 4, 12, 24, 36, and 52 weeks after implantation. Improvements from the baseline scores were evaluated using the equation “(postoperative score) − (preoperative score).” Magnetic resonance imaging (MRI) was performed at 2, 12, 24, and 52 weeks after implantation, and MRI measurements were evaluated using T1 rho and T2 mapping. ResultsNine patients were enrolled in this study and were examined for safety. Product quality did not satisfy the specification in one patient, and bacterial joint infection occurred in one patient. As a result, seven patients were included in the outcome analyses. The mean IKDC score significantly improved from 36.4 preoperatively to 74.1% at 52 weeks after implantation (p < 0.0001). The mean Lysholm and VAS scores also significantly improved from 39.6 to 57.4 to 89.6 and 22.9, respectively, after surgery. In the MRI evaluation, the T1 rho and T2 values of the implanted area were similar to those of the surrounding cartilage at 52 weeks after implantation. ConclusionsThird generation ACI (IK-01) can be an effective treatment option for focal cartilage defects of the knee; however, surgeons must pay careful attention to the risk of postoperative joint infection.

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.

Third-Generation Autologous Chondrocyte Implantation at the Knee Joint Using the Igor Scaffold: A Case Series With 2-Year Follow-up.

Background:For large, locally restricted cartilage defects in young patients, third-generation matrix-supported autologous chondrocyte implantation (ACI) with a variety of scaffolds has shown good mid- to long-term results.Purpose/Hypothesis:This study aimed to monitor the clinical and radiological outcomes of patients who received ACI at the knee joint using the Igor scaffold (IGOR–Institute for Tissue and Organ Reconstruction) at 2-year follow-up. Our hypothesis was that there would be improvements in postoperative subjective scores and cartilage repair tissue quality.Study Design:Case series; Level of evidence, 4.Methods:A total of 21 patients (12 male and 9 female) were available for 2-year follow-up after third-generation ACI using the Igor scaffold. All were clinically assessed using the Knee injury and Osteoarthritis Outcome Score (KOOS), Tegner Activity Scale, Brittberg score, International Knee Documentation Committee (IKDC) Subjective Knee Form, Noyes Sports Activity Rating Scale, and visual analog scale for pain. For morphological evaluation, the magnetic resonance observation of cartilage repair tissue (MOCART) and MOCART 2.0 scores were calculated using 3-T magnetic resonance imaging performed at 3, 6, 12, and 24 months postoperatively. Results were compared between baseline and 24 months postoperatively.Results:After 2 years, the clinical and radiological scores showed good to excellent results in the majority of patients. On the IKDC, 10 patients were graded as excellent, 4 as good, 5 as fair, and 2 as severe; on the KOOS, 7 patients were graded as excellent, 8 as good, 4 as fair, and 2 as severe. From baseline to latest follow-up, visual analog scale pain scores decreased from 5.6 ± 3.2 (mean ± SD) to 1.5 ± 2; KOOS results increased from 51 ± 20.7 to 75.2 ± 15.4; and the Tegner score improved from 2.2 ± 1.8 to 4.3 ± 1.3. The MOCART and MOCART 2.0 scores were comparable at 2-year follow-up, with mean values of 74 ± 10 and 78 ± 13, respectively. Satisfactory filling and integration were found in 90.5%. Overall, 16 of 21 patients (76.1%) were satisfied with the surgery and would undergo the procedure again.Conclusion:Third-generation ACI using the Igor scaffold showed improvements in clinical and radiological results that were comparable with other scaffolds for patients with large traumatic or degenerative cartilage defects. Patients reported a decrease in pain and an increase in activity, with the majority reporting good results.

Effect of the defect localization and size on the success of third-generation autologous chondrocyte implantation in the knee joint

IntroductionFemoral and patellar cartilage defects with a defect size > 2.5 cm2 are a potential indication for an autologous chondrocyte implantation (ACI). However, the influence of the localization and the absolute and relative defect size on the clinical outcome has not yet been determined. The purpose of this study is to analyze the influence of the localization and the absolute and relative defect size on the clinical outcome after third-generation autologous chondrocyte implantation.MethodsA total of 50 patients with cartilage defects of the knee were treated with third-generation autologous chondrocyte implantation (Novocart® 3D). A match paired analysis was performed of 25 treated femoral and 25 treated patella defects with a follow-up of three years. MRI data was used to do the manual segmentation of the cartilage layer throughout the knee joint. The defect size was determined by taking the defect size measured in the MRI in relation to the whole cartilage area. The clinical outcome was measured by the IKDC score and VAS pre-operatively and after six, 12, 24, and 36 months post-operatively.ResultsIKDC and VAS scores showed a significant improvement from the baseline in both groups. Femoral cartilage defects showed significantly superior clinical results in the analyzed scores compared to patellar defects. The femoral group improved IKDC from 33.9 (SD 18.1) pre-operatively to 71.5 (SD 17.4) after three years and the VAS from 6.9 (SD 2.9) pre-operatively to 2.4 (SD 2.5) after three years. In the patellar group, IKDC improved from 36.1 (SD 12.6) pre-operatively to 54.7 (SD 20.3) after three years and the VAS improved from 6.7 (SD 2.8) pre-operatively to 3.4 (SD 2.) after three years. Regarding the defect size, results showed that the same absolute defect size at med FC (4.8, range 2–15) and patella (4.6, range 2–12) has a significantly different share of the total cartilaginous size of the joint compartment (med FC: 6.7, range 1.2–13.9; pat: 18.9, range 4.0–47.0). However, there was no significant influence of the relative defect size on the clinical outcome in either patellar or femoral localization.ConclusionThird-generation autologous chondrocyte implantation in ACI-treated femoral cartilage defects leads to a superior clinical outcome in a follow-up of three years compared with patellar defects. No significant influence of the defect size was found in either femoral or patellar cartilage defects.

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.

Third generation autologous chondrocyte implantation is a good treatment option for athletic persons

PurposeAutologous chondrocyte implantation is an established method for the treatment of joint cartilage damage. However, to date it has not been established that autologous chondrocyte implantation is an appropriate procedure for cartilage defects therapy in athletic persons. The aim of this study is to analyze if third-generation autologous chondrocyte implantation is an appropriate treatment for athletic persons with full cartilage defect of the knee joints.MethodsA total of 84 patients were treated with third-generation autologous chondrocyte implantation (NOVOCART® 3D). The mean follow-up time was 8 years (5–14). Sports activity was measured via UCLA Activity Score and Tegner Activity Scale before the onset of knee pain and postoperatively in an annual clinical evaluation. 41 athletic persons and 43 non-athletic persons (UCLA-Cut-off: 7; Tegner Activity Scale-Cut-off: 4) were analyzed. Patient reported outcomes were captured using IKDC subjective, KOOS, Lysholm score and VAS score on movement.ResultsPatient reported outcomes (IKDC, VAS at rest, VAS on movement) showed significant improvement (p < 0.001) postoperatively. Athletic persons demonstrated significantly better results than non-athletic persons in the analyzed outcome scores (IKDC: p < 0.01, KOOS: p < 0.01, Lysholm score: p < 0.01). 96.4% of the patients were able to return to sport and over 50% returned or surpassed their preinjury sports level. The remaining patients were downgraded by a median of two points on the UCLA- and 2.5 on the Tegner Activity Scale. A shift from high-impact sports to active events and moderate or mild activities was found. Furthermore, it was shown that preoperative UCLA score and Tegner Activity Scale correlated significantly with the patient reported outcome postoperatively.ConclusionAutologous chondrocyte implantation is a suitable treatment option for athletic persons with full-thickness cartilage defects in the knee. The return to sports activity is possible, but includes a shift from high-impact sports to less strenuous activities.

Patient-Reported and Magnetic Resonance Imaging Outcomes of Third-Generation Autologous Chondrocyte Implantation After 10 Years

To evaluate the long-term clinical and radiologic outcomes of third-generation autologous chondrocyte implantation (ACI) for the treatment of focal cartilage defects of the knee. Data capture was carried out between 2004 and 2018. Included were patients with cartilage defects of the knee joint with an International Cartilage Repair Society grade of III or higher treated with third-generation ACI who had a minimum follow-up period of 10 years. International Knee Documentation Committee scores and assessment of pain at rest and on movement using visual analog scale scores were captured preoperatively and at 6 months postoperatively, as well as annually thereafter. In addition, we performed magnetic resonance imaging examinations in 13 cases after 10 years. The MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score was used to evaluate the ACI cartilage. A total of 54 patients met the inclusion criteria. Of these, 30 reached the 10-year follow-up point and were included in this assessment. At 10 years postoperatively, all clinical outcome parameters showed a statistically significant improvement compared with the preoperative situation, with a responder rate of 70%. The average MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score after 10 years was 59.2 points (range, 20-100 points), and over 60% of the evaluated patients showed good integration of the implant at 10 years postoperatively. The clinical and radiologic findings of this study show that third-generation ACI is a suitable and effective option in the treatment of full-thickness cartilage defects of the knee. At 10 years after surgery, third-generation ACI shows stable results and leads to significant improvement in all clinical outcome parameters. Despite these results, revision surgery after third-generation ACI is common and was needed in 23% of patients in this study. Level IV, therapeutic case series.

Third-generation autologous chondrocyte implantation after failed bone marrow stimulation leads to inferior clinical results.

Third-generation autologous chondrocyte implantation (ACI) is an established and frequently used method and successful method for the treatment of full-thickness cartilage defects in the knee. There are also an increasing number of patients with autologous chondrocyte implantation as a second-line therapy that is used after failed bone marrow stimulation in the patient's history. The purpose of this study is to investigate the effect of previous bone marrow stimulation on subsequent autologous chondrocyte implantation therapy. In this study, the clinical results after the matrix-based autologous chondrocyte implantation in the knee in a follow-up over 3years postoperatively were analysed. Forty patients were included in this study. A total of 20 patients with cartilage defects of the knee were treated with third-generation autologous chondrocyte implantation (Novocart® 3D) as first-line therapy. The mean defect size was 5.4 cm2 (SD 2.6). IKDC subjective score and VAS were used for clinical evaluation after 6, 12, 24 and 36months postoperatively. The results of these patients were compared with 20 matched patients with autologous chondrocyte implantation as second-line therapy. Matched pair analysis was performed by numbers of treated defects, defect location, defect size, gender, age and BMI. Both the first-line (Group I) and second-line group (Group II) showed significantly better clinical results in IKDC score and VAS score in the follow-up over 3years compared with the preoperative findings. In addition, Group I showed significantly better results in the IKDC and VAS during the whole postoperative follow-up after 6, 12, 24 and 36months compared to Group II with second-line autologous chondrocyte implantation (IKDC 6months p = 0.015, 1year p = 0.001, 2years p = 0.001, 3years p = 0.011). Additionally, we found a lower failure rate in Group I. No revision surgery was performed in Group I. The failure rate in the second-line Group II was 30%. This study showed that third-generation autologous chondrocyte implantation is a suitable method for the treatment of full-thickness cartilage defects. Both, Group I and Group II showed significant improvement in our follow-up. However, in comparing the results of the two groups, autologous chondrocyte implantation after failed bone marrow stimulation leads to worse clinical results. III.

Matrix-Induced Autologous Chondrocyte Implantation With Autologous Bone Grafting for Osteochondral Lesions of the Femoral Trochlea

Matrix-induced autologous chondrocyte implantation is a 2-stage surgical procedure used to treat symptomatic, full-thickness chondral lesions of the knee. This third-generation autologous chondrocyte implantation (ACI) technique improves on the limitations of previous methods, including the risk of uneven chondrocyte distribution at the time of implantation and graft hypertrophy. Given the compliant properties of the scaffold, the graft can be easily shaped to treat irregular chondral defects and applied to articular surfaces with multiplanar geometry (e.g., patella, trochlea). Although ACI techniques are ideally suited to treat chondral surface defects, the ACI “sandwich” technique can be used to treat large osteochondral defects with significant bone loss (>8 mm). Historically, this procedure uses autologous bone graft to replace areas of osseous deficiency along with 2 type I/III collagen bilayer membranes to securely contain the cultured chondrocytes within the defect. We present an analogous technique for the treatment of osteochondral lesions of the femoral trochlea using a single matrix-induced ACI scaffold and autologous bone grafting for a segmental osseous defect.

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.

Autologous Chondrocyte Implantation (ACI) for Knee Cartilage Defects: A Review of Indications, Technique, and Outcomes.

* Autologous chondrocyte implantation (ACI) was first developed in the late 1980s for the treatment of articular cartilage defects in the knee. The first generation of ACI utilized a periosteal patch to contain the cultured chondrocyte solution within the defect. Because of issues with periosteal graft hypertrophy, ACI with use of a collagen membrane patch (second-generation ACI) was developed. Finally, the application of chondrocytes within a matrix (third-generation ACI) was created to improve cell delivery, to allow for minimally invasive implantation, to better replicate normal cartilage architecture, and to accelerate patient rehabilitation. As of December 2016, only 1 third-generation ACI product (matrix-induced autologous chondrocyte implantation, or MACI) has been cleared for marketing by the U.S. Food and Drug Administration (FDA) and is available in the United States.* ACI (regardless of generation) is effective for the treatment of high-grade tibiofemoral cartilage defects. However, issues with coronal alignment, ligament laxity/instability, and meniscal deficiency must be addressed or the outcomes following ACI will be poor.* Because of the extended time that is required for graft maturation, special consideration must be given to return-to-play protocols as athletes can regain strength and neuromuscular coordination well before the graft has sufficiently matured.

Comparison of Collagen Graft Fixation Methods in the Porcine Knee: Implications for Matrix-Assisted Chondrocyte Implantation and Second-Generation Autologous Chondrocyte Implantation

To evaluate the fixation integrity at time zero of a type I/III collagen patch secured to a chondral defect in the porcine knee using methods typically employed in autologous chondrocyte implantation (ACI) and matrix-assisted chondrocyte implantation. Twenty-four porcine knee specimens underwent a medial parapatellar arthrotomy. A prefabricated template was used to create cartilage defects of 2 cm(2) in the medial femoral condyle. A size-matched collagen patch was fashioned. Four methods of fixation to the chondral defect were analyzed: group 1-saline, group 2-fibrin glue around the periphery of the patch, group 3-fibrin glue applied to the base of the defect and around the periphery of the patch, group 4-6-0 vicryl suture and fibrin glue around the periphery of the patch. Collagen patch fixation was assessed at intervals of 60, 300, 600, 900, and 1,200 cycles from full extension to 90° of flexion, performed manually without application of axial force. Patch fixation was evaluated by 2 independent observers using a customized scoring scale. Mean peripheral detachment of the patch and chondral defect uncovering remained less than 25% for all groups. Area of defect uncovering was significantly increased in group 2 compared with group 4 after 900 and 1,200 cycles (P= .0014 and P= .0025, respectively). Fibrin glue applied to the base of the defect, or suturing of the patch, reduced deformation significantly after 900 cycles. Suture increases the stability of fixation of a type I/III collagen patch to a chondral defect better than fibrin glue alone in the porcine knee after repetitive cycling, with respect to patch detachment and chondral defect uncovering. Application of fibrin glue to the base of the defect, or securing the patch with suture, decreases collagen patch deformation. In cases where minimally invasive techniques do not allow suture fixation of the collagen patch, scaffold fixation may be compromised during articular motion protocols typically used after second- and third-generation ACI procedures.

Autologous chondrocyte implantation: Is it likely to become a saviour of large-sized and full-thickness cartilage defect in young adult knee?

A literature review of the first-, second- and third-generation autologous chondrocyte implantation (ACI) technique for the treatment of large-sized (>4cm(2)) and full-thickness knee cartilage defects in young adults was conducted, examining the current literature on features, clinical scores, complications, magnetic resonance image (MRI) and histological outcomes, rehabilitation and cost-effectiveness. A literature review was carried out in the main medical databases to evaluate the several studies concerning ACI treatment of large-sized and full-thickness knee cartilage defects in young adults. ACI technique has been shown to relieve symptoms and improve functional assessment in large-sized (>4cm(2)) and full-thickness knee articular cartilage defect of young adults in short- and medium-term follow-up. Besides, low level of evidence demonstrated its efficiency and durability at long-term follow-up after implantation. Furthermore, MRI and histological evaluations provided the evidence that graft can return back to the previous nearly normal cartilage via ACI techniques. Clinical outcomes tend to be similar in different ACI techniques, but with simplified procedure, low complication rate and better graft quality in the third-generation ACI technique. ACI based on the experience of cell-based therapy, with the high potential to regenerate hyaline-like tissue, represents clinical development in treatment of large-sized and full-thickness knee cartilage defects. IV.

Bone Marrow Edema in the Knee and Its Influence on Clinical Outcome After Matrix-Based Autologous Chondrocyte Implantation

Background: Third-generation autologous chondrocyte implantation (ACI) is an established method for treatment of full-thickness cartilage defects in the knee joint. Subchondral bone marrow edema (BME) is frequently observed after ACI, with unknown pathogenesis and clinical relevance. Purpose: To investigate the occurrence and clinical relevance of BME after third-generation ACI in the knee joint during the postoperative course of 36 months. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 38 circumscribed full-thickness cartilage defects in 30 patients were included in this study. All defects were treated with third-generation ACI (Novocart 3D). A standardized MRI examination was carried out after 1.5, 3, 6, 12, 24, and 36 months. Bone marrow edema was observed in 78.9% of defects over the postoperative course, with initial occurrence in the first 12 months. The size of the BMEs were determined according to their maximum diameter and were classified as small (<1 cm), medium (<2 cm), large (<4 cm), and very large (diffuse; >4 cm). Clinical outcomes in patients were analyzed by use of the International Knee Documentation Committee (IKDC) scoring system and a visual analog scale for pain. Results: There were 5.3% (n = 2) small, 28.9% (n = 11) medium, 34.2% (n = 13) large, and 10.5% (n = 4) very large BMEs. In a subgroup analysis, cartilage defects of the medial femoral condyle showed significantly higher frequency of BME than did patellar defects. Clinical scores showed significant improvements throughout the entire study course (P < .05). Clinical patient outcome did not correlate with presence of BME at any time period (P > .05). Conclusion: Midterm clinical results of the matrix-based third-generation ACI showed a substantial amount of BME over a 36-month follow-up, but this did not correlate with worse clinical outcome. Patients with femoral cartilage defects were more often affected than were those with patellar cartilage defects.

A systematic review of reporting of rehabilitation in articular-cartilage-repair studies of third-generation autologous chondrocyte implantation in the knee.

Autologous chondrocyte implantation (ACI) is a tissue-engineered surgical technique initially developed for articular cartilage repair of isolated chondral lesions of the knee. Third-generation techniques (ACI3) are now available that deliver autologous cultured chondrocytes into the defect using cell scaffolds. The successful outcomes of these techniques have some dependency on presurgical and postsurgical patient rehabilitation. To determine if the standard of reporting for rehabilitation has improved in ACI3 studies; previous reviews in this field recommended describing the detail of this rehabilitation and patient compliance as integral elements. A computerized search was performed in March 2013. Criteria for inclusion were any studies that evaluated or described the process of ACI3 in the knee and subsequent rehabilitation. The modified Coleman Methodology Score (CMS) was used to rate the standard of reporting of rehabilitation and surgical procedures; review articles were also evaluated for quality using the Strength of Recommendation Taxonomy (SORT). Mean scores, odds ratios, 95% confidence intervals, and Mann-Whitney U statistics were calculated. An improvement in mean CMS was seen compared with previous reviews, but rehabilitation reporting scores were lower than their surgical equivalent; significant association was seen between studies with rehabilitator involvement and high scores in the individual CMS rehabilitation element. Predominant SORT scores of 2A indicated medium strength of recommendation. The CMS provides a general overview of methodological quality, but a more specialized tool to report on the quantitative and qualitative aspects of the rehabilitation process would help raise the standards. It is recommended that rehabilitation therapists be included as key members of research teams and be involved in the design, implementation, and reporting of future studies.

ISAKOS Upper Extremity Committee Shoulder Rotator Cuff Consensus, Plus Chondrocyte Implantation and ACL Systematic Reviews

ISAKOS Upper Extremity Committee Shoulder Rotator Cuff Consensus, Plus Chondrocyte Implantation and ACL Systematic Reviews

Do meta-analyses reveal time-dependent differences between the clinical outcomes achieved by microfracture and autologous chondrocyte implantation in the treatment of cartilage defects of the knee?

PurposeTo test the hypothesis that autologous chondrocyte implantation (ACI) has a better treatment effect than microfracture (MF), and increasing superiority over the years, when performed under similar patient-specific and defect-specific conditions. MethodsWe scanned four electronic databases for controlled clinical trials or controlled prospective observational studies. We conducted random-effects meta-analyses of equivalent data using standardized mean differences as the outcome measure of choice at 1, 2, and 5-year follow-up. We assessed heterogeneity with the I2 index and publication bias with funnel plots and Kendall’s tests. ResultsOur literature search revealed six study populations (nine papers) which satisfied our eligibility criteria. Overall, 399 patients aged between 16 and 60years with 1–10cm2 chondral defects were available. The MF and the ACI study groups were well matched regarding patient baseline characteristics. For all papers, microfracture was performed according to Steadman, whereas three generations of ACI were applied. When all were combined, non-significant superiority of ACI over MF was revealed; surprisingly, this superiority decreased over the years. However, our meta-analyses combining solely second and third-generation ACI revealed significant standardized differences, becoming smaller over the years, but always representing a large effect. Nevertheless, our approximate estimate of the difference between the treatment effects provoked by second and third-generation ACI and by MF is not indicative of clinically relevant superiority of ACI over MF at 5-year follow-up. ConclusionsBoth series of meta-analyses (combining either all ACI modifications or solely the second and third generations of ACI) suggest that the treatment effects resulting from ACI and MF converge over the years.