Freeze-Dried Curdlan/Whey Protein Isolate-Based Biomaterial as Promising Scaffold for Matrix-Associated Autologous Chondrocyte Transplantation—A Pilot In-Vitro Study

The purpose of this pilot study was to establish whether a novel freeze-dried curdlan/whey protein isolate-based biomaterial may be taken into consideration as a potential scaffold for matrix-associated autologous chondrocyte transplantation. For this reason, this biomaterial was initially characterized by the visualization of its micro- and macrostructures as well as evaluation of its mechanical stability, and its ability to undergo enzymatic degradation in vitro. Subsequently, the cytocompatibility of the biomaterial towards human chondrocytes (isolated from an orthopaedic patient) was assessed. It was demonstrated that the novel freeze-dried curdlan/whey protein isolate-based biomaterial possessed a porous structure and a Young’s modulus close to those of the superficial and middle zones of cartilage. It also exhibited controllable degradability in collagenase II solution over nine weeks. Most importantly, this biomaterial supported the viability and proliferation of human chondrocytes, which maintained their characteristic phenotype. Moreover, quantitative reverse transcription PCR analysis and confocal microscope observations revealed that the biomaterial may protect chondrocytes from dedifferentiation towards fibroblast-like cells during 12-day culture. Thus, in conclusion, this pilot study demonstrated that novel freeze-dried curdlan/whey protein isolate-based biomaterial may be considered as a potential scaffold for matrix-associated autologous chondrocyte transplantation.

Early Efficacy of Type I Collagen-Based Matrix-Assisted Autologous Chondrocyte Transplantation for the Treatment of Articular Cartilage Lesions

Background: Articular cartilage is a complex structure that allows for low frictional gliding and effective shock absorption. Various sports injuries and inflammatory conditions can lead to lesions in the articular cartilage, which has limited regenerative potential. Type I collagen combined with autologous chondrocytes in a three-dimensional culture were used to induce the regeneration of single-layer autologous expanded chondrocytes without chondrogenic differentiation.Purpose: To assess the clinical, radiological, and histological changes following collagen-based autologous chondrocyte transplantation (MACT) for chondral knee lesions.Methods: The study prospectively enrolled 20 patients with symptomatic knee chondral lesions (mean size lesion was 2.41 ± 0.43 cm2, range: 2.0–3.4 cm2) in the lateral femoral condyle and femoral groove who underwent type I collagen-based MACT between July 2017 and July 2019. knee injury and osteoarthritis outcome score (KOOS) was assessed before the procedure, and periodic clinical follow-up was conducted every 3 months for a maximum of 12 months following the procedure and at 1-year intervals thereafter. Magnetic resonance imaging (MRI) T2 mapping of repaired cartilage was also used for the quantitative analysis of regeneration. In one patient, second-look arthroscopy was performed to assess cartilage regeneration characteristics, and a portion of regenerated cartilage was harvested for histological evaluation 12 months after implantation.Results: At pre-operation and at three, six, 12, and 24 months after the operation, KOOS pain, symptoms, daily life activities, sports and recreation, as well as the quality of life were significantly improved between every two time points. Hematoxylin and eosin (HE) staining indicated that the newly formed cartilage was comprised of naive chondrocytes. Safranin O-fast (S-O) green staining of the regenerated tissue revealed fibroblast-like cells surrounded by glycosaminoglycans. Immunohistochemistry (IHC) analysis indicated that collagen type II was uniformly distributed at the deep zone of articular cartilage and type I collagen mainly depositing in the superficial cartilage layer. The T2 values for repaired tissue gradually decreased, eventually approaching near-average values.Conclusion: The present study demonstrated that type I collagen-based MACT is a clinically effective treatment for improving functionality and pain levels. Histological evidence confirmed hyaline cartilage induction and showed that repaired cartilage tended to emerge from the deep to the superficial layer. The quantitative MRI T2 mapping test indicated that there still was a difference between the transplanted cartilage and the surrounding hyaline cartilage. Taken together, the current method represents an efficient approach for the restoration of knee cartilage lesions.

Clinical evaluation after matrix-associated autologous chondrocyte transplantation

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/m2 (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 cm2 (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.

Arthroscopic Matrix-Assisted Autologous Chondrocyte Transplantation Versus Microfracture: A 6-Year Follow-up of a Prospective Randomized Trial

Background: Few randomized controlled trials with a midterm follow-up have compared matrix-assisted autologous chondrocyte transplantation (MACT) with microfracture (MFx) for knee cartilage lesions. Purpose: To compare the structural, clinical, and safety outcomes at midterm follow-up of MACT versus MFx for treating symptomatic knee cartilage lesions. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 48 patients aged between 18 and 50 years, with 1- to 4-cm2 International Cartilage Repair Society (ICRS) grade III to IV knee chondral lesions, were randomized in a 1:1 ratio to the MACT and MFx treatment groups. A sequential prospective evaluation was performed using magnetic resonance imaging (MRI) T2 mapping, the MOCART (magnetic resonance observation of cartilage repair tissue) score, second-look arthroscopic surgery, patient-reported outcome measures, the responder rate (based on achieving the minimal clinically important difference for the Knee injury and Osteoarthritis Outcome Score [KOOS] pain and KOOS Sport/Recreation), adverse events, and treatment failure (defined as a reoperation because of symptoms caused by the primary defect and the detachment or absence of >50% of the repaired tissue during revision surgery). Results: Overall, 35 patients (18 MACT and 17 MFx) with a mean chondral lesion size of 1.8 ± 0.8 cm2 (range, 1-4 cm2) were followed up to a mean of 6 years postoperatively (range, 4-9 years). MACT demonstrated significantly better structural outcomes than MFx at 1 to 6 years postoperatively. At final follow-up, the MRI T2 mapping values of the repaired tissue were 37.7 ± 8.5 ms for MACT versus 46.4 ± 8.5 ms for MFx ( P = .003), while the MOCART scores were 59.4 ± 17.3 and 42.4 ± 16.3, respectively ( P = .006). More than 50% defect filling was seen in 95% of patients at 2 years and 82% at 6 years in the MACT group and in 67% at 2 years and 53% at 6 years in the MFx group. The second-look ICRS scores at 1 year were 10.7 ± 1.3 for MACT and 9.0 ± 1.8 for MFx ( P = .001). Both groups showed significant clinical improvements at 6 years postoperatively compared with their preoperative status. Significant differences favoring the MACT group were observed at 2 years on the KOOS Activities of Daily Living ( P = .043), at 4 years on all KOOS subscales (except Symptoms; P < .05) and the Tegner scale ( P = .008), and at 6 years on the Tegner scale ( P = .010). The responder rates at 6 years were 53% and 77% for MFx and MACT, respectively. There were no reported treatment failures after MACT; the failure rate was 8.3% in the MFx group. Neither group had serious adverse events related to treatment. Conclusion: Patients who underwent MACT had better structural outcomes than those who underwent MFx at 1 to 6 years postoperatively. Both groups of patients showed significant clinical improvements at final follow-up compared with their preoperative status. MACT showed superiority at 4 years for the majority of the KOOS subscales and for the Tegner scale at 4 to 6 years. The MACT group also had a higher responder rate and lower failure rate at final follow-up. Registration: NCT01947374 ( ClinicalTrials.gov identifier).

Early Efficacy of Type I Collagen Based Matrix-Assisted Autologous Chondrocyte Transplantation to Treat Articular Cartilage Lesions

Purpose: To investigate the clinical, radiological, and histological results of type I collagen-based matrix-assisted autologous chondrocyte transplantation (MACT) in the treatment of chondral lesions of the knee.Methods: The study prospectively enrolled 20 patients with symptomatic knee chondral defects (mean size defect was 2.41±0.43 cm2, range 2.0 to 3.4 cm2) in the lateral femoral condyle and femoral groove who underwent type I collagen-based MACT between July 2017 and July 2019. KOOS was assessed preoperatively, with periodic clinical follow-up performed preoperatively and then every 3 months for up to 12 months postoperative period, and thereafter at 1-year intervals. During this follow-up, serial magnetic resonance imaging T2 mapping of repair cartilage was used to reflect the quantitative analysis quality of the regenerative cartilage. In one patient, second-look arthroscopy was performed at 12 months after implantation to assess the characteristics of cartilage regeneration.Results: Compared with preoperation, the score of the pain, symptoms, activities of daily living, sports and recreation, and quality of life showed statistically significant improvement with a significant difference at 3, 6, 12, and 24 months after operation(P<0.05). The difference in KOOS subscales scores between every two-time point was statistically significant (P<0.001). HE stains showed the newly formed cartilage was naive chondrocytes. Safranin O-fast green stain manifested in the regenerated tissue comprising predominantly fibroblast-like cells surrounded by glycosaminoglycans. Immunohistochemistry analysis showed that the expression of collagen type II was more clearly and evenly distributed than collagen type I.Conclusion: Type I collagen-based MACT was a clinically effective treatment for functional and pain level improvement, and this method presented histologic evidence of inducing hyaline‐like cartilage in cartilage lesions by biopsy in one case. The quantitative MRI T2-mapping test showed that there was a difference between the transplanted cartilage and the surrounding hyaline cartilage.

Long-term Results of Arthroscopic Matrix-Assisted Autologous Chondrocyte Transplantation: A Prospective Follow-up at 15 Years

Background: Matrix-assisted autologous chondrocyte transplantation (MACT) procedures have been developed to overcome some of the limits of first-generation autologous chondrocyte implantation. However, while good autologous chondrocyte implantation results have been documented over time, data are scarce on the long-term MACT results. Purpose: To evaluate long-term clinical results of a large cohort of patients treated with hyaluronic acid–based MACT for articular cartilage defects of the knee. Study Design: Case series; Level of evidence, 4. Methods: A long-term evaluation of 113 patients was performed (91 men, 22 women; mean ± SD age, 29.0 ± 10.6 years) for 115 knees affected by chondral and osteochondral lesions of the femoral condyles and trochlea. Of these, 61 knees had undergone previous surgery, while other procedures were combined during the same operation in 48 knees. These patients were prospectively evaluated before surgery and at 2, 5, and 10 years after surgery, as well as at a final mean follow-up of 15 years (range, 12-18 years), with various clinical scores: International Knee Documentation Committee (IKDC), EuroQol visual analog scale (EQ-VAS), and Tegner. Both surgical and clinical failures were documented. Results: The IKDC subjective score increased from the basal level of 39.9 ± 14.6 (mean ± SD) to 77.3 ± 20.5 ( P < .0005) at 2 years; results remained stable up to the 15-year follow-up (76.9 ± 20.5). EQ-VAS and Tegner scores showed a statistically significant improvement up to 10 years, with a further significant improvement at the final follow-up. A failure rate of 15.0% was documented, which increased to 21.7% when clinical failures were also considered. A worse outcome was found for older age ( P < .0005), female sex ( P = .002), degenerative lesions ( P < .0005), longer duration of symptoms ( P = .005), and previous surgery ( P < .0005). Conclusion: Arthroscopic MACT offered good and long-lasting results that were stable over time and resulted in a limited number of failures and reinterventions for up to 15 years of follow-up. Several factors were identified as having a prognostic value: a worse outcome could be expected in older patients, female patients, those affected by lesions with a degenerative cause, those having a longer duration of symptoms, and patients who underwent previous surgery.

Three-dimensional, Scaffold-Free, Autologous Chondrocyte Transplantation: A Systematic Review

Background: A 3-dimensional, scaffold-free, and completely autologous form of chondrocyte transplantation (ACT3D) has been developed and applied in clinical practice in the past decade to overcome disadvantages of previous-generation procedures. Purpose: To document and analyze the available literature on the results of ACT3D in the treatment of articular chondral lesions in the knee and hip joints. Study Design: Systematic review; Level of evidence, 4. Methods: All studies published in English addressing ACT3D were identified and included those that fulfilled the following criteria: (1) level 1 through 4 evidence, (2) measures of radiological or functional/clinical outcome, and (3) outcome related to cartilage lesions of the knee and hip joints. Results: A total of 10 studies were selected: 2 randomized controlled trials, 1 cohort study, and 7 case series. The studies revealed significant increases in patients’ subjective quality of life, satisfaction, pain reduction, and improvement in joint function at short- to medium-term follow-up. Magnetic resonance imaging-assisted examination and second-look arthroscopy showed a hyaline-like repair tissue with a high degree of defect filling and integration. Conclusion: ACT3D shows promising results in the therapy of articular cartilage defects in the knee as well as in the hip, but well-designed, long-term studies are lacking. ACT3D might have relevant advantages over common matrix-associated autologous chondrocyte transplantation products, but systematic evaluation and randomized controlled studies are crucial to verify the potential of this tissue-engineered approach.