Decellularized Stem Cell Matrix: A Novel Approach for Autologous Chondrocyte Implantation-Based Cartilage Repair

Author(s):  
Jingting Li ◽  
Ming Pei
2019 ◽  
Vol 7 (7) ◽  
pp. 232596711985444 ◽  
Author(s):  
Philipp Niemeyer ◽  
Volker Laute ◽  
Wolfgang Zinser ◽  
Christoph Becher ◽  
Thomas Kolombe ◽  
...  

Background:Autologous chondrocyte implantation (ACI) and microfracture are established treatments for large, full-thickness cartilage defects, but there is still a need to expand the clinical and health economic knowledge of these procedures.Purpose:To confirm the noninferiority of ACI compared with microfracture.Study Design:Randomized controlled trial; Level of evidence, 2.Methods:Patients were randomized to be treated with matrix-associated ACI using spheroid technology (n = 52) or microfracture (n = 50). Both procedures followed standard methods. Patients were assessed by the Knee injury and Osteoarthritis Outcome Score (KOOS), MOCART (magnetic resonance observation of cartilage repair tissue) scoring system, Bern score, modified Lysholm score, International Cartilage Repair Society (ICRS) rating (histological and immunochemical scoring after rebiopsy 24 months after implantation), and International Knee Documentation Committee (IKDC) examination form. The main assessments were conducted 24 months after study treatment.Results:In the primary intention-to-treat analysis, the overall KOOS score for both ACI and microfracture yielded a statistically significant improvement relative to baseline. According to the between-group analysis, ACI passed the test of noninferiority compared with microfracture; thus, the primary goal of the study was achieved. The KOOS subscores yielded the same qualitative results as the overall KOOS score (ie, for each of these, noninferiority was demonstrated), and in 1 case (Activities of Daily Living subscore), the threshold for superiority was passed. The subgroup analyses did not yield any clear evidence of an association between treatment effect and any of the categories investigated (age, diagnosis, defect localization, sex). A histological analysis of biopsies from 16 patients (ACI: n = 9; microfracture: n = 7) suggested a better quality of repair in the patients treated with ACI.Conclusion:The efficacy of both ACI and microfracture was demonstrated with respect to both functional outcomes and morphological repair. The primary analysis confirmed the statistical hypothesis of the noninferiority of ACI, even for relatively small cartilage defects (1-4 cm2) treated in this study, the indication for which microfracture is generally accepted as the standard of care. ACI showed significant superiority in the KOOS subscores of Activities of Daily Living at 24 months and Knee-related Quality of Life at 12 months.Registration:NCT01222559 ( ClinicalTrials.gov identifier).


Cartilage ◽  
2020 ◽  
pp. 194760352091863
Author(s):  
Enrique Villalobos ◽  
Antonio Madrazo-Ibarra ◽  
Valentín Martínez ◽  
Anell Olivos-Meza ◽  
Cristina Velasquillo ◽  
...  

Objective. To evaluate minimum biosecurity parameters (MBP) for arthroscopic matrix-encapsulated autologous chondrocyte implantation (AMECI) based on patients’ clinical outcomes, magnetic resonance imaging (MRI) T2-mapping, Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and International Cartilage Repair Society (ICRS) second-look arthroscopic evaluation, laying the basis for a future multicenter study. Design. Pilot clinical study. We analyzed the logistics to perform AMECI to treat focal chondral lesions in different hospitals following strict biosecurity parameters related to tissue and construct transportation, chondrocyte isolation, and cell expansion. Patient progress was analyzed with patient-reported outcome measures, MRI T2-mapping, MOCART, and ICRS arthroscopic second-look evaluation. Results. Thirty-five lesions in 30 patients treated in 7 different hospitals were evaluated. Cell viability before implantation was >90%. Cell viability in construct remnants was 87% ± 11% at 24 hours, 75% ± 17.1% at 48 hours, and 60% ± 8% at 72 hours after implantation. Mean final follow-up was 37 months (12-72 months). Patients showed statistically significant improvement in all clinical scores and MOCART evaluations. MRI T2-mapping evaluation showed significant decrease in relaxation time from 61.2 ± 14.3 to 42.9 ± 7.2 ms ( P < 0.05). Arthroscopic second-look evaluation showed grade II “near normal” tissue in 83% of patients. Two treatment failures were documented. Conclusions. It was feasible to perform AMECI in 7 different institutions in a large metropolitan area following our biosecurity measures without any implant-related complication. Treated patients showed improvement in clinical, MRI T2-mapping, and MOCART scores, as well as a low failure rate and a favorable ICRS arthroscopic evaluation at a mid-term follow-up. Level of Evidence. 2b.


2019 ◽  
Vol 47 (13) ◽  
pp. 3212-3220 ◽  
Author(s):  
Takahiro Ogura ◽  
Tim Bryant ◽  
Gergo Merkely ◽  
Brian A. Mosier ◽  
Tom Minas

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.


Cartilage ◽  
2019 ◽  
pp. 194760351983589 ◽  
Author(s):  
Juan Manuel López-Alcorocho ◽  
Isabel Guillén-Vicente ◽  
Elena Rodríguez-Iñigo ◽  
Ramón Navarro ◽  
Rosa Caballero-Santos ◽  
...  

Purpose Two-year follow-up to assess efficacy and safety of high-density autologous chondrocyte implantation (HD-ACI) in patients with cartilage lesions in the ankle. Design Twenty-four consecutive patients with International Cartilage repair Society (ICRS) grade 3-4 cartilage lesions of the ankle were included. Five million chondrocytes per cm2 of lesion were implanted using a type I/III collagen membrane as a carrier and treatment effectiveness was assessed by evaluating pain with the visual analogue scale (VAS) and American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score at baseline, 12-month, and 24-month follow-up, together with dorsal and plantar flexion. Magnetic resonance observation for cartilage repair tissue (MOCART) score was used to evaluate cartilage healing. Histological study was possible in 5 cases. Results Patients’ median age was 31 years (range 18-55 years). Median VAS score was 8 (range 5-10) at baseline, 1.5 (range 0-8) at 12-month follow-up, and 2 (rang e0-5) at 24-month follow-up ( P < 0.001). Median AOFAS score was 39.5 (range 29-48) at baseline, 90 (range 38-100) at 12-month follow-up, and 90 (range 40-100) at 24-month follow-up ( P < 0.001). Complete dorsal flexion significantly increased at 12 months (16/24, 66.7%) and 24 months (17/24, 70.8%) with regard to baseline (13/24, 54.2%) ( P = 0.002). MOCART at 12- and 24-month follow-ups were 73.71 ± 15.99 and 72.33 ± 16.21. Histological study confirmed that neosynthetized tissue was cartilage with hyaline extracellular matrix and numerous viable chondrocytes. Conclusion HD-ACI is a safe and effective technique to treat osteochondral lesions in the talus, providing good clinical and histological results at short- and mid-term follow-ups.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Ashvin K. Dewan ◽  
Matthew A. Gibson ◽  
Jennifer H. Elisseeff ◽  
Michael E. Trice

Articular cartilage defects have been addressed using microfracture, abrasion chondroplasty, or osteochondral grafting, but these strategies do not generate tissue that adequately recapitulates native cartilage. During the past 25 years, promising new strategies using assorted scaffolds and cell sources to induce chondrocyte expansion have emerged. We reviewed the evolution of autologous chondrocyte implantation and compared it to other cartilage repair techniques.Methods. We searched PubMed from 1949 to 2014 for the keywords “autologous chondrocyte implantation” (ACI) and “cartilage repair” in clinical trials, meta-analyses, and review articles. We analyzed these articles, their bibliographies, our experience, and cartilage regeneration textbooks.Results. Microfracture, abrasion chondroplasty, osteochondral grafting, ACI, and autologous matrix-induced chondrogenesis are distinguishable by cell source (including chondrocytes and stem cells) and associated scaffolds (natural or synthetic, hydrogels or membranes). ACI seems to be as good as, if not better than, microfracture for repairing large chondral defects in a young patient’s knee as evaluated by multiple clinical indices and the quality of regenerated tissue.Conclusion. Although there is not enough evidence to determine the best repair technique, ACI is the most established cell-based treatment for full-thickness chondral defects in young patients.


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