Matrix-induced Autologous Chondrocyte Implantation Research Articles

Autologous chondrocyte implantation, matrix-induced autologous chondrocyte implantation, osteochondral autograft transplantation and osteochondral allograft improve knee function and pain with considerations for patient and cartilage defects characteristics: A systematic review and meta-analysis.

Previous studies have reported on the outcomes of autologous chondrocyte implantation (ACI) versus matrix-induced ACI (MACI) and microfracture. Specific clinical outcomes of ACI, MACI, osteochondral autograft transplantation (OAT) and osteochondral allograft (OCA) have not been well studied. The purpose of this systematic review and meta-analysis was to analyze the outcomes of these regenerative surgical techniques with an emphasis on comparing their effectiveness using the International Knee Documentation Committee (IKDC) subjective score, the Lysholm Knee Scoring Scale, the Tegner Activity Scale and the Visual Analogue Scale (VAS) score for the surgical treatment of tibiofemoral joint cartilage defects. An electronic search of MEDLINE, Embase and Cochrane Library was performed to identify studies that reported clinical outcomes for ACI, MACI, OAT and OCA procedures. The literature review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and only studies involving cartilage defects in the tibiofemoral joint were included. Outcomes were measured with the IKDC evaluation, Lysholm Knee Scoring Scale, Tegner Activity Scale and the VAS. Outcomes were compared to the minimal clinically important difference (MCID) and patient acceptable symptom state (PASS). The methodological quality of the included studies was analyzed by the Methodological Index for Nonrandomized Studies and the Jadad scale. Forty-seven studies were included representing a total of 1993 patients with a mean follow-up time of 57.2 ± 40.3 months (range: 4.0-160.0 months). The location of cartilage defects was reported in 46 studies, with a total of 1922 cartilage defects. There were 1277 medial femoral condyle cartilage defects, 488 lateral femoral condyle cartilage defects, 139 unspecified femoral condyle cartilage defects and 18 tibial plateau cartilage defects. All four procedures reported significant improvements in the Lysholm, IKDC, Tegner and VAS scores with no significant differences between them. The OAT technique surpassed the PASS threshold for the IKDC score while all four techniques surpassed the PASS threshold for Tegner and Lysholm scores. Additionally, all procedures met the MCID for each clinical outcome. This systematic review and meta-analysis indicate that ACI, MACI, OAT and OCA all result in significant improvements in knee function and pain for cartilage defects of the tibiofemoral joint. When selecting a procedure, patient and cartilage defect characteristics should be assessed to determine the best technique for each individual patient. Systematic review and meta-analysis. Level III.

Bone marrow edema-like signal after cartilage repair does not affect outcomes in a five-year follow-up.

Bone marrow edema-like signal (BMELS) after cartilage repair is common, but its clinical significance remains uncertain. This study aimed to investigate the clinical and structural significance of BMELS following microfracturing (MFX) and matrix-induced autologous chondrocyte implantation (MACI). In this multicenter study, MRI examinations were performed over a period of 5 years after cartilage repair surgery (MFX n = 17; MACI n = 28) in 45 patients. Morphological assessments, including the MOCART 2.0 (magnetic resonance observation of cartilage repair tissue), quantitative imaging biomarkers (QIB) with T2 mapping of the repair tissue, and, specifically, assessment of the presence and size of BMELS, were conducted along with patient-reported outcome measures, such as the Knee injury and Osteoarthritis Outcome Score (KOOS) and the International Knee Documentation Committee (IKDC). BMELS structural and clinical assessments were obtained after 3 months, 12 months, and 60 months. Statistical analysis included the Mann-Whitney U-test, Wilcoxon rank test, Shapiro-Wilk test, and simulation-based power analysis. BMELS were a common finding 60 months after cartilage repair. The size of BMELS differed significantly only between MACI and MFX patients after 3 months, with larger BMELS occurring in the MFX group. There were no significant differences in patients with or without BMELS regarding the T2 ratio of the treated area, the MOCART 2.0, or clinical scores. BMELS frequently appeared after cartilage repair procedures. We could show that the postoperative size and change in the size of BMELS after MACI and MFX did not affect clinical scores, morphological MRI results, or biochemical properties of the treated area after 60 months. Question What is the clinical significance of bone marrow edema-like signal (BMELS) appearance after matrix-induced autologous chondrocyte implantation (MACI) or microfracture (MFX)? Finding There were no significant differences in patients with or without BMELS regarding the T2 ratio of the treated area, the MOCART 2.0, or clinical scores. Clinical relevance BMELS frequently appeared after cartilage repair, the appearance or the size dynamic after MACI and MFX did not affect clinical scores, morphological MRI results, or biochemical properties after 60 months.

Factors Influencing Long-term Outcomes After Matrix-Induced Autologous Chondrocyte Implantation: Long-term Results at 10 Years

Background: Matrix-induced autologous chondrocyte implantation (MACI), the third-generation of the technique, is an established procedure for the treatment of focal cartilage defects in the knee. However, the literature lacks long-term results of MACI with good statistical power. Purpose: To determine long-term survival and patient-reported outcomes (PROs) in a representative cohort and to identify patient- and surgery-related parameters that may influence long-term clinical outcomes. Study Design: Case series; Level of evidence, 4. Methods: A total of 103 patients were clinically evaluated at the current follow-up of 8.1 years (range, 5-11.9 years). PRO measures (PROMs) included the Knee injury and Osteoarthritis Outcome Score (KOOS), EQ-5D, visual analog scale for pain, and Tegner Activity Scale. Magnetic resonance imaging results were evaluated by using the AMADEUS (area measurement and depth and underlying structures) and MOCART (magnetic resonance observation of cartilage repair tissue) 2.0 knee score classification systems. Potential factors influencing PROs were first identified univariately and investigated in a multivariate regression model. Results: The defects had a mean size of 4.8 cm2 (range, 1.2-12 cm2) and were predominantly femorotibial (66%). The mean Kaplan-Meier survival rate of revision for any reason was 97.2% ± 1.6% at 10 years. In comparison to preoperative values, all PROMs were significantly improved at the current follow-up (P < .05). The MOCART 2.0 score peaked at 12 months (mean, 80.2 ± 15.3 months) and showed no significant change at 96 months (mean, 76.1 ± 19.5 months; P = .142). The linear multivariate regression model identified an association of body mass index (BMI), MOCART 2.0 score, and number of previous knee surgeries with KOOS (R2 = 0.41; f2 = 0.69). Further analysis of the individual determinants revealed an optimal BMI range of 20 to 29 for favorable PROs at 96 months. Significant correlations of MOCART subscores with the overall KOOS were found for graft surface and structure, bony reaction, and subchondral detectable changes. Only 30% of patients with2 previous surgeries and 20% of patients with 3 previous surgeries achieved a Patient Acceptable Symptom State (χ2 = 10.93; P = .012). Conclusion: The present study shows consistently good long-term clinical outcomes after MACI with a low revision rate and high patient satisfaction. BMI and number of previous knee surgeries may influence clinical outcomes and should be considered in patient selection and education. There is a correlation between graft structure, subchondral bone changes on magnetic resonance imaging, and long-term PROMs.

Analysis of Patients Who Undergo Index Arthroscopy With Biopsy but Not Implantation for Staged Chondrocyte Cell Transplantation.

Autologous chondrocyte implantation (ACI) and matrix-induced autologous chondrocyte implantation (MACI) are 2-stage procedures requiring an index full-thickness cartilage biopsy. Only a portion of patients ultimately undergo second-stage ACI/MACI. To identify patients with articular cartilage defects who underwent arthroscopic debridement with biopsy for ACI/MACI and compare those who did with those who did not proceed with implantation within 2 years after biopsy. Additionally, the authors sought to identify why patients did not proceed with implantation. Case-control study; Level of evidence, 3. Patients who underwent arthroscopy and autologous chondrocyte biopsy from January 1, 2015, to December 31, 2019, and who had minimum 2-year follow-up data were grouped into those who proceeded with second-stage ACI/MACI (implant group; n = 97) and those who did not (biopsy group; n = 63). Demographic factors, cartilage defect characteristics, and preoperative International Knee Documentation Committee (IKDC) scores were analyzed. Patients in both groups were evaluated postoperatively using the IKDC, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Single Assessment Numeric Evaluation (SANE), and visual analog scale (VAS) for pain, and patients who did not undergo implantation were asked for their reasoning. Body mass index (BMI) (P < .001) and Outerbridge grades at index arthroscopy (P = .047) were significantly higher for the implant group than the biopsy group. Both groups had significantly improved IKDC scores from their initial presentation to final follow-up (implant group: 46.4 ± 16.2 preoperative vs 69.6 ± 20.6 postoperative [P < .001]; biopsy group: 47.2 ± 15.9 preoperative vs 70.7 ± 19.1 postoperative [P < .001]); however, the level of improvement did not differ significantly between groups. Postoperative WOMAC, SANE, and VAS pain scores were also similar between groups. In the biopsy group, 23 patients (37%) cited symptom resolution or activity level improvement after initial arthroscopy as the reason for not proceeding with implantation. Patients who proceeded to the second stage of chondrocyte implantation via either ACI or MACI had higher-grade articular defects and higher BMI compared with those who underwent biopsy with concomitant debridement chondroplasty alone. Postoperative outcomes were similar between the groups.

More negative sagittal tibial tuberosity-trochlear groove distances are correlated with larger patellofemoral chondral lesion size.

The purpose of this study is to assess the association between sagittal tibial tuberosity-trochlear groove (sTT-TG) distance and patellofemoral chondral lesion size in patients undergoing cartilage restoration procedures. A retrospective cohort analysis of patients who underwent an osteochondral allograft transplantation or matrix-induced autologous chondrocyte implantation in the patellofemoral compartment, from 2010 to 2020, were included if they had patellofemoral high-grade lesions, magnetic resonance imaging (MRI) and minimum 2-year follow-up. The preoperative sTT-TG distance was measured independently on axial T2-weighted MRI sequences by two authors, each at least two weeks apart. Intraoperative lesion size was reported according to operative report measurements by the attending surgeon. An interclass correlation coefficient (ICC) was calculated to assess intra- and inter-rater reliability, and categorical data analysis and linear regression models were used to assess the relationship between sTT-TG and lesion size. A total of 80 patients (50 females) with a mean age of 31.5 ± 10.4 years, body mass index of 27.0 ± 5.9 kg/m2 and follow-up of 61.5 ± 21.4 months were included. A total of 107 lesions were present: 63 patients with unipolar (patella = 41, trochlea = 22) and 22 with bipolar lesions. The mean MRI defect size was 1.6 ± 1.0 cm2 and the mean intraoperative defect size was 3.8 ± 2.4cm2. Intra- (ICC: 0.99,0.98) and inter-rater reliability (ICC: 0.96) were excellent for both MRI defect size and sTT-TG measurements. The mean sTT-TG was -4.8 ± 4.9 mm and was significantly inversely related to MRI defect size (-0.45, p < 0.01), intraoperative patellar lesion size (-0.32, p = 0.01), total lesion area (-0.22, p = 0.04), but not trochlear lesion size (-0.09, p = 0.56). Multivariable regression demonstrated a more negative sTT-TG remained an independent variable correlated with larger MRI-measured patellofemoral defect sizes and intraoperative patellar lesions. A more negative sTT-TG was an independent variable correlated with larger patellofemoral lesions in patients undergoing patellofemoral cartilage restoration. Level III, Diagnostic.

Management of patellar and trochlear cartilage lesions with matrix-induced autologous chondrocyte implantation in conjunction with patellofemoral realignment procedures improves patient-reported outcomes and magnetic resonance image appearance

ObjectivesThe aim of this study is to evaluate the relationship between the achievement of clinically significant improvement in patient-reported outcome measures (PROMs) and the postoperative magnetic resonance image (MRI) appearance of matrix-associated chondrocyte implantation (MACI), in conjunction with patellofemoral realignment procedures, for the treatment of grade-IV chondral defects about the patellofemoral joint. MethodsA retrospective review of patients undergoing MACI for grade-IV chondral defects of the patella or trochlea by a single sports-medicine-fellowship-trained surgeon from 2017 to 2020 was performed. Concomitant realignment procedures, including tibial tubercle osteotomy and medial patellofemoral ligament reconstruction, were also performed as needed. Patients with preoperative and minimum 1-year postoperative PROMs and postoperative knee MRI were included. MRI scans were obtained at 6.3 (interquartile range: 5.8, 7.5) months postoperatively. A fellowship-trained musculoskeletal radiologist assigned a Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score (range: 0–100, with 100 equating to complete graft healing) to each MRI. Achievement of the minimal clinically important difference (MCID) for International Knee Documentation Committee (IKDC), Knee Injury and Osteoarthritis Score—Quality of Life, and Kujala scores were determined for each patient. Paired t-tests or Wilcoxon rank-sum tests were used to evaluate for an association between achievement of the MCID for each PROM and MOCART score. The average follow-up time and time from surgery to PROMs were 2.7 ​± ​1.5 years and 1.7 ​± ​0.66 years, respectively. ResultsThirty patients were included. There was a significant improvement in all PROMs from preoperative to postoperative (p ​< ​0.001). More than two-thirds of patients achieved the MCID for each PROM. Patients who achieved the MCID for IKDC had significantly higher MOCART scores (66.5 ​± ​16.2) than those who did not meet the MCID for IKDC (50.6 ​± ​23.6, p ​= ​0.043). ConclusionMACI for the treatment of patellofemoral chondral injuries is associated with clinically significant improvement in PROMs at short-term follow-up. Clinically significant improvements in IKDC scores are associated with a more mature MRI appearance of the autologous chondrocyte implantation graft on postoperative MRI, as indicated by higher MOCART scores. Level of evidenceIV—Case Series.

Clinical and Radiological Outcomes at ≥10-Year Follow-up After Matrix-induced Autologous Chondrocyte Implantation in the Patellofemoral Joint

Background: Matrix-induced autologous chondrocyte implantation (MACI) has demonstrated encouraging outcomes in the treatment of knee cartilage defects, although limited research is available on its longer term (≥10 years) sustainability in the patellofemoral joint. Purpose: To report the clinical and radiological outcomes at ≥10 years in a prospectively recruited cohort of patients undergoing MACI in the patellofemoral joint and compare outcomes in patients undergoing MACI on the patella versus the trochlea. Study Design: Case series; Level of evidence, 4. Methods: The current study prospectively enrolled 95 patients who underwent patellofemoral MACI, of whom 29 (13 patella, 16 trochlea) underwent concomitant tibial tubercle osteotomy. Patients were assessed preoperatively and at 2, 5, and ≥10 years using a range of patient-reported outcome measures (PROMs) including the Knee injury and Osteoarthritis Outcome Score, the 36-item Short Form Health Survey, and the frequency and severity of knee pain as well as patient satisfaction, full active knee flexion and extension, and peak isokinetic knee extensor and flexor torques. High-resolution magnetic resonance imaging (MRI) was performed to assess pertinent graft parameters, as well as determine an overall MRI composite score, per the Magnetic Resonance Observation of Cartilage Repair Tissue scoring system. Results were analyzed according to the graft location (patella or trochlea). Results: Of the 95 patients recruited, 82 patients (41 patella, 41 trochlea) were available for a clinical review at ≥10 years after surgery (mean follow-up, 11.9 years [range, 10-15 years]). For the whole patellofemoral MACI cohort, all PROMs significantly improved over time (P < .05), with no significant changes (P > .05) observed in any MRI-based score from 2 to ≥10 years after surgery. At ≥10 years, 90.2% (n = 74) were satisfied with MACI in relieving their knee pain, and 85.4% (n = 70) were satisfied with the improvement in their ability to participate in sports. No differences (P > .05) were observed in PROMs between those undergoing patellar MACI and those undergoing trochlear MACI, although a significant group effect was observed for limb symmetry indices of knee extensor (P = .009) and flexor (P = .041) strength, which were greater in those undergoing patellar (vs trochlear) MACI. No statistically significant differences (P > .05) were observed between patellar and trochlear grafts on any MRI-based measure. In the cohort assessed at ≥10 years after surgery, 4 patients (2 patella, 2 trochlea) demonstrated graft failure on MRI scans, although a further 3 patients (all trochlea) were omitted from the ≥10-year review for having already progressed to total knee arthroplasty. Conclusion: Good clinical scores, high levels of patient satisfaction, and adequate graft survivorship were observed at ≥10 years after MACI on the patella and trochlea.

Optimization of Collagen Scaffold with Cultured Autologous Chondrocytes for Osteochondritis Dissecans of the Knee: A Case Report

The treatment of osteochondritis dissecans of the knee has always been a challenge for orthopedic surgeons. We present a case report of a 38-year-old male with severe right knee pain after suffering from an indirect trauma and axial rotation of the knee, limiting knee functionality and impeding his ability to walk, with a diagnosis of osteochondritis dissecans in the trochlea of the knee, who underwent arthroscopic treatment with matrix-induced autologous chondrocyte implantation (MACI). After the surgery, a physical therapy protocol for MACI was implemented, and magnetic resonance images with cartilage mapping were used to evaluate the recovery of the lesion. A total recovery was observed and evaluated with the modified Cincinnati knee rating system (mCKRS). A discussion is provided with evidence and general recommendations for the use of MACI in the treatment of adult OCD of the knee as a possible alternative to conventional treatments. Our case shows a rapid improvement in pain and functionality 2 months after surgery that progressed to full recovery within 6 months.

Advances in clinical repair techniques for localized knee cartilage lesions

To summarize the classic and latest treatment techniques for localized knee cartilage lesions in clinical practice and create a new comprehensive clinical decision-making process. The advantages and limitations of various treatment methods for localized knee cartilage lesions were summarized by extensive review of relevant literature at home and abroad in recent years. Currently, there are various surgical methods for treating localized knee cartilage injuries in clinical practice, each with its own pros and cons. For patients with cartilage injuries less than 2 cm 2 and 2-4 cm 2 with bone loss are recommended to undergo osteochondral autograft (OAT) and osteochondral allograft (OCA) surgeries. For patients with cartilage injuries less than 2 cm 2 and 2-4 cm 2 without bone loss had treatment options including bone marrow-based techniques (micro-fracture and ogous matrix induced chondrogenesis), autologous chondrocyte implantation (ACI)/matrix-induced ACI, particulated juvenile allograft cartilage (PJAC), OAT, and OCA. For patients with cartilage injuries larger than 4 cm 2 with bone loss were recommended to undergo OCA. For patients with cartilage injuries larger than 4 cm 2 without bone loss, treatment options included ACI/matrix-induced ACI, OAT, and PJAC. There are many treatment techniques available for localized knee cartilage lesions. Treatment strategy selection should be based on the size and location of the lesion, the extent of involvement of the subchondral bone, and the level of evidence supporting each technique in the literature.

Poster 227: Prospective Clinical and Radiological Follow-Up Beyond 10 Years in Patients Undergoing Matrix-Induced Autologous Chondrocyte Implantation (MACI) in the Patellofemoral Joint

Objectives: Matrix-induced autologous chondrocyte implantation (MACI) has demonstrated encouraging outcomes in the treatment of knee cartilage defects, though limited research is available on its longer-term (≥10 years) sustainability in the patellofemoral joint. This prospective study sought to present and report the clinical and radiological outcome beyond 10 years in a prospectively recruited cohort of patients undergoing MACI in the patellofemoral knee joint. Methods: The current study included 82 patients (patella = 41, trochlea = 41) assessed at ≥10 years following patellofemoral MACI. Patients were assessed preoperatively and at 2, 5 and ≥10 years via the Knee Injury and Osteoarthritis Outcome score (KOOS), the 36-item Short Form Health Survey (SF-36), the frequency (VAS-F) and severity (VAS-S) of knee pain, patient satisfaction, active knee range of motion (ROM) and peak isokinetic knee extensor and flexor torque. High-resolution magnetic resonance imaging (MRI) assessed pertinent measures of graft outcome as per the magnetic resonance observation of cartilage repair tissue (MOCART) system, as well as an overall MRI composite score. Results were analyzed according to the graft location (patella or trochlea). Results: While no statistically significant differences (p&gt;0.05) were observed between those undergoing patella or trochlea MACI across the majority of demographic (age, weight, BMI), injury history (duration of symptoms) or surgery (defect size, prior procedures, requirement for concomitant patellofemoral re-alignment) variables, a significantly higher (p=0.013) proportion of males was seen in the trochlea MACI group. All patient-reported outcome measures significantly improved (p&lt;0.05), with no differences observed between those undergoing patella or trochlea MACI. No group differences (p&gt;0.05) were observed in active knee flexion or extension ROM between groups, though those undergoing patella (versus trochlea) MACI demonstrated significantly greater postoperative quadriceps (Figure 1) and hamstring strength limb symmetry indices. No statistically significant decline (p&gt;0.05) was seen from 2 years to final follow-up in any MRI-based measure, with no MRI-based differences observed between patella (Figure 2) and trochlea (Figure 3) grafts. In the cohort assessed at ≥10 years post-surgery, 4 patients (patella n=2, trochlea n=2) demonstrated graft failure on MRI, though a further 3 patients (all trochlea) were omitted from ≥10-year review that had already progressed toward total knee arthroplasty. Conclusions: Good clinical scores, high levels of patient satisfaction and adequate graft survivorship were observed at ≥10 years following MACI to the patella or trochlea.

Paper 38: Comparison of Clinical Outcomes and Return to Sport Rates Between Osteochondral Allograft Transplantation and Autologous Chondrocyte Implantation for Articular Cartilage Lesions in the Patellofemoral Joint

Objectives: The purpose of this study is to compare clinical outcomes and return to sport (RTS) rates between patients that undergo osteochondral allograft (OCA) transplantation and autologous chondrocyte implantation (ACI), or matrix-induced autologous chondrocyte implantation (MACI), for patellofemoral articular cartilage defects. Methods: A retrospective review of patients who underwent an OCA, ACI, and MACI from 2010 to 2020 with a minimum two-year follow-up was conducted. Patient-reported outcomes (PROs) collected included: Visual Analog Scale for pain and satisfaction, Knee Injury and Osteoarthritis Outcome Score (KOOS), and return to sport (RTS) status. Logistic regression controlling for age, sex, BMI, bone marrow edema, mechanism of injury, lesions size and location was used to identify predictors of worse outcomes. Results: A total of 95 patients with a mean age of 32.1 years (± 10.0) and mean BMI of 26.5 (± 5.9) were included. ACI or MACI was performed in 55 cases (57.9%) and OCA in 40 (42.1%). Satisfaction was not significantly different between groups. VAS pain scores were higher in the OCA group, but did not reach significance. Overall, KOOS pain was significantly poorer in the OCA group than the ACI/MACI group, while KOOS symptoms, KOOS sport, and KOOS QOL subscores were non-significantly different. Overall, RTS rate was 54.3.%, with no significant difference in return between OCA or ACI/MACI groups. Increasing age was associated with lower satisfaction in the OCA group and poorer outcomes in the ACI/MACI group, while larger lesion area was associated with lower satisfaction and poorer outcomes scores in the ACI/MACI group. Conclusions: Clinical outcomes and return to sport rates are similar in patients that undergo OCA or ACI/MACI for patellofemoral articular cartilage defects, except in measures of pain, where patients undergoing OCA may experience more symptoms, particularly in the setting of trochlear defects.

Comparable Clinical and Functional Outcomes Between Osteochondral Allograft Transplantation and Autologous Chondrocyte Implantation for Articular Cartilage Lesions in the Patellofemoral Joint at a Mean Follow-up of 5 Years

To assess clinical outcomes and return to sport (RTS) rates among patients who undergo osteochondral allograft (OCA) transplantation and autologous chondrocyte implantation (ACI) or matrix-induced autologous chondrocyte implantation (MACI), for patellofemoral articular cartilage defects. A retrospective review of patients who underwent an OCA or ACI/MACI from 2010 to 2020 was conducted. Patient-reported outcomes collected included visual analog scale for pain/satisfaction, Knee Injury and Osteoarthritis Outcome Score (KOOS), and RTS. The percentage of patients that met the patient acceptable symptom state for KOOS was recorded. Logistic regression was used to identify predictors of worse outcomes. A total of 95 patients were included (78% follow-up) with ACI or MACI performed in 55 cases (57.9%) and OCA in 40 (42.1%). A tibial tubercle osteotomy was the most common concomitant procedure for OCA (66%) and ACI/MACI (98%). Overall, KOOS pain was significantly poorer in OCA than ACI/MACI (74.7, 95% confidence interval 68.1-81.1 vs 83.6, 95% confidence interval 81.3, 88.4, P= .012), whereas the remaining KOOS subscores were nonsignificantly different (all P > .05). Overall, RTS rate was 54%, with no significant difference in return between OCA or ACI/MACI (52% vs 58%, P= .738). There were 26 (27%) reoperations and 5 (5%) graft failures in the entire group. Increasing age was associated with lower satisfaction in OCA and poorer outcomes in ACI/MACI, whereas larger lesion area was associated with lower satisfaction and poorer outcomes in ACI/MACI. Clinical and functional outcomes were similar in patients who underwent OCA or ACI/MACI for patellofemoral articular cartilage defects at a mean follow-up of 5 years. Patients who received OCA had a greater proportion of degenerative cartilage lesions and, among those with trochlear lesions, reported greater pain at final follow-up than their ACI/MACI counterparts. Overall, increasing age and a larger lesion size were associated with worse patient-reported outcomes. Level III, retrospective cohort study.

Rates and predictors of reimplantation of matrix-induced autologous chondrocyte implantation following first stage cartilage harvest: A cohort study

PurposeTo assess the reimplantation rate and predictors of patients requiring second-staged matrix-induced autologous chondrocyte implantation (MACI) reimplantation after initial first stage cartilage biopsy. MethodsA retrospective review was performed from 2018 to 2022 among patients who underwent only phase I MACI biopsy procedure (biopsy group) or both phase I with transition to phase II implantation of chondrocytes (implantation group) at a single tertiary center. Demographic, qualitative, and quantitative measurements were recorded, and univariate and multivariate regression analysis was performed to assess predictors of ultimately requiring second stage MACI implantation. ResultsA total of 71 patients (51% female, age 27.7 ± 10.6 years (range 12–50)) were included in this study. Eventually, 25 of 71 patients (35.2%) experienced persistence of symptoms after initial MACI biopsy and other concomitant procedures, requiring second-stage implantation. Univariate analysis showed the implantation group compared to the biopsy group had a greater lesion size (5.2 cm2 ± 3.3 vs. 3.3 cm2 ± 1.4, p = 0.024), a higher proportion patients ≥ 26 years of age (76% vs. 43%, p = 0.009), a medial femoral condyle lesion more commonly (33% vs 11%, p = 0.005), were more often female (72% vs. 39%, p = 0.008), and had less often soft tissue repair at time of biopsy (32% vs. 61%, p = 0.020). Backward multivariate logistic regression analysis revealed that size of the lesion (OR 1.43, p = 0.031) and age ≥ 26 years old at time of biopsy (OR 3.55, p = 0.042) were independent predictors of not responding to initial surgery and requiring implantation surgery. ConclusionThis study found that 35% of patients undergoing MACI phase I biopsy harvest eventually required autologous implantation. Independent risk factors for progressing to implantation after failed initial surgery were larger defect size and older age.Level of Evidence: III, Cohort Study.

New horizons in cartilage repair: update on treatment trends and outcomes

IntroductionArticular cartilage plays a crucial role in preserving the knee joint's structural integrity. Damage can manifest as focal chondral defects or progressive osteoarthritis. Treatment options for knee cartilage damage are multifaceted, encompassing surgical and nonsurgical interventions to repair defects, alleviate symptoms, restore function, and slow disease progression. ObjectivesGain insight and summarize the latest available evidence of knee joint preservation techniques. MethodsThe indications, outcomes, and biological characteristics of operative and nonoperative knee cartilage repair and joint preservation therapies were summarized. ResultsOsteochondral autologous transplantation and osteochondral allograft transplantation offer durable solutions with excellent long-term outcomes. Autologous chondrocyte implantation and matrix-induced autologous chondrocyte implantation are advanced, cell-based therapies effective for larger defects, especially in younger, active individuals. Non-operative therapies such as hyaluronic acid provide symptomatic relief for knee osteoarthritis. Bone marrow aspirate concentrate and platelet-rich plasma show efficacy in alleviating symptoms and improving joint function, presenting a minimally invasive approach with promising results for knee preservation and cartilage repair. ConclusionThe use of minimally invasive and nonsurgical interventions in addressing focal cartilage defects, osteoarthritis, and overall joint preservation has yielded varied results. Although recent literature has exhibited encouraging findings, the existing body of high-level evidence remains limited. The emerging evidence inspires optimism for the future, as medical practitioners shift focus to the next wave of knee cartilage repair and joint preservation methodologies. However, comprehensive research is essential to establish conclusive insights into outcomes, safety profiles, and comparative effectiveness among the diverse available treatments.

10-Year Prospective Clinical and Radiological Evaluation After Matrix-Induced Autologous Chondrocyte Implantation and Comparison of Tibiofemoral and Patellofemoral Graft Outcomes

Background: Long-term outcomes in larger cohorts after matrix-induced autologous chondrocyte implantation (MACI) are required. Furthermore, little is known about the longer-term clinical and radiological outcomes of MACI performed in the tibiofemoral versus patellofemoral knee joint. Purpose: To present the 10-year clinical and radiological outcomes in patients after MACI and compare outcomes in patients undergoing tibiofemoral versus patellofemoral MACI. Study Design: Case series; Level of evidence, 4. Methods: Between September 2002 and December 2012, 204 patients who underwent MACI were prospectively registered into a research program and assessed preoperatively and at 2, 5, and 10 years postoperatively. Of these patients, 168 were available for clinical review at 10 years, with 151 (of a total of 182) grafts also assessed via magnetic resonance imaging (MRI). Patients were evaluated using the Knee injury and Osteoarthritis Outcome Score, a visual analog scale for pain frequency and severity, satisfaction, and peak isokinetic knee extensor and flexor strength. Limb symmetry indices (LSIs) were calculated for strength measures. Grafts were scored on MRI scans via the MOCART (magnetic resonance observation of cartilage repair tissue) system, with a focus on tissue infill and an overall MRI graft composite score. Results: All patient-reported outcome measures improved (P < .0001) up to 2 years after surgery. Apart from the significant increase (P = .004) in the peak isokinetic knee extensor LSI, no other patient-reported outcome measure or clinical score had changed significantly from 2 to 10 years. At the final follow-up, 92% of patients were satisfied with MACI to provide knee pain relief, with 76% satisfied with their ability to participate in sports. From 2 to 10 years, no significant change was seen for any MRI-based MOCART variable nor the overall MRI composite score. Of the 151 grafts reviewed via MRI at 10 years, 14 (9.3%) had failed, defined by graft delamination or no graft tissue on MRI scan. Furthermore, of the 36 patients (of the prospectively recruited 204) who were not available for longer-term review, 7 had already proceeded to total knee arthroplasty, and 1 patient had undergone secondary MACI at the same medial femoral condylar site because of an earlier graft failure. Therefore, 22 patients (10.8%) essentially had graft failure over the period. At the final follow-up, patients who underwent MACI in the tibiofemoral (vs patellofemoral) joint reported significantly better Knee injury and Osteoarthritis Outcome Score subscale scores for Quality of Life (P = .010) and Sport and Recreation (P < .001), as well as a greater knee extensor strength LSI (P = .002). Even though the tibiofemoral group demonstrated better 10-year MOCART scores for tissue infill (P = .027), there were no other MRI-based differences (P > .05). Conclusion: This study reports the long-term review of a prospective series of patients undergoing MACI, demonstrating good clinical scores, high levels of patient satisfaction, and acceptable graft survivorship at 10 years. Patients undergoing tibiofemoral (vs patellofemoral) MACI reported better long-term clinical outcomes, despite largely similar MRI-based outcomes.

Epigenetic Priming Enhances Chondrogenic Potential of Expanded Chondrocytes.

Expansion of chondrocytes presents a major obstacle in the cartilage regeneration procedure, such as matrix-induced autologous chondrocyte implantation. Dedifferentiation of chondrocytes during the expansion process leads to the emergence of a fibrotic (chondrofibrotic) phenotype that decreases the chondrogenic potential of the implanted cells. We aim to (1) determine the extent that chromatin architecture of H3K27me3 and H3K9me3 remodels during dedifferentiation and persists after the transfer to a three-dimensional (3D) culture; and (2) to prevent this persistent remodeling to enhance the chondrogenic potential of expanded bovine chondrocytes, used as a model system. Chromatin architecture remodeling of H3K27me3 and H3K9me3 was observed at 0 population doublings, 8 population doublings, and 16 population doublings (PD16) in a two-dimensional (2D) culture and after encapsulation of the expanded chondrocytes in a 3D hydrogel culture. Chondrocytes were treated with inhibitors of epigenetic modifiers (epigenetic priming) for PD16 and then encapsulated in 3D hydrogels. Chromatin architecture of chondrocytes and gene expression were evaluated before and after encapsulation. We observed a change in chromatin architecture of epigenetic modifications H3K27me3 and H3K9me3 during chondrocyte dedifferentiation. Although inhibiting enzymes that modify H3K27me3 and H3K9me3 did not alter the dedifferentiation process in 2D culture, applying these treatments during the 2D expansion did increase the expression of select chondrogenic genes and protein deposition of type II collagen when transferred to a 3D environment. Overall, we found that epigenetic priming of expanded bovine chondrocytes alters the cell fate when chondrocytes are later encapsulated into a 3D environment, providing a potential method to enhance the success of cartilage regeneration procedures.

Minimum 10-Year Outcomes of Matrix-Induced Autologous Chondrocyte Implantation in the Knee: A Systematic Review.

Matrix-induced autologous chondrocyte implantation (MACI) is an established cell-based therapy for the treatment of chondral defects of the knee. As long-term outcomes are now being reported in the literature, it is important to systematically review available evidence to better inform clinical practice. To report (1) subjective patient-reported outcomes (PROs) and (2) the rate of graft failure, reoperation, and progression to total knee arthroplasty (TKA) after undergoing MACI of the knee at a minimum 10-year follow-up. Systematic review; Level of evidence, 4. A comprehensive search of Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily; Ovid Embase; Ovid Cochrane Central Register of Controlled Trials; Ovid Cochrane Database of Systematic Reviews; and Scopus from 2008 to September 15, 2022, was conducted in the English language. Study eligibility criteria included (1) full-text articles in the English language, (2) patients undergoing a MACI within the knee, (3) clinical outcomes reported, and (4) a minimum 10-year follow-up. In total, 168 patients (99 male, 69 female; mean age, 37 years [range, 15-63 years]; mean body mass index, 26.2 [range, 18.6-39.4]) representing 188 treated chondral defects at a minimum 10-year follow-up after MACI were included in this review. Significant and durable long-term improvements were observed across multiple PRO measures. Follow-up magnetic resonance imaging (MRI), when performed, also demonstrated satisfactory defect fill and an intact graft in the majority of patients. The all-cause reoperation rate was 9.0%, with an overall 7.4% rate of progression to TKA at 10 to 17 years of follow-up. At a minimum 10-year follow-up, patients undergoing MACI for knee chondral defects demonstrated significant and durable improvements in PROs, satisfactory defect fill on MRI-based assessment, and low rates of reoperation and TKA. These data support the use of MACI as a long-term treatment of focal cartilage defects of the knee.

MACI Sandwich Technique With Autologous Bone Graft

Background: Osteochondral lesions of the knee are difficult to manage. Such lesions can be effectively treated with the matrix-induced autologous chondrocyte implantation (MACI) “sandwich” technique using autologous chondrocytes on porcine collagen membrane in conjuction with autologous cancellous bone grafting (ABG). Few studies have examined this technique to restore the osteochondral unit. Indications: The MACI “Sandwich” procedure is indicated when osteochondral lesions are larger than 2 cm2 in size and deeper than 8 to 10 mm, with symptoms consistent with the location of the lesion. Technique Description: The chondral defect is radically debrided back to healthy bone and cartilage tissue. The base of the bony cavity is drilled to enhance the vascular supply and promote healing. Next, the bony cavity is prepared to slightly undermine the subchondral bone surface around the articular margins, with the depth of the cavity wider than the opening, similar to a dental amalgam. The autologous cancellous bone is subsequently morselized and impacted up to the level of the native subchondral bone plate. The first MACI membrane with the cells facing up is placed directly onto the bone graft site and compressed with a neural patty. The neural patty is removed, and the second MACI membrane is then placed with the cells facing down. The edges are then micro-sutured to ensure stability. Results: The “sandwich” technique has superior survival rates compared with autologous bone grafting alone, with patients reporting decreased pain, improved function, and high satisfaction scores over a mid-term to long-term follow-up. Discussion/Conclusion: The MACI “sandwich” technique is an effective surgical intervention to restore the osteochondral unit and preserve the patient's native knee joint. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Return to Play After Knee Articular Cartilage Restoration: Surgical Options, Rehabilitation Protocols, and Performance Outcomes.

Numerous cartilage restoration techniques have proven to be effective in the treatment of articular cartilage defects. The ultimate goal of these procedures is to improve pain and function, thereby increasing the likelihood of a patient's return to physical activity. Postoperative rehabilitation is a key component for a successful and expedient return to activities. The purpose of this article is to review the current literature regarding common surgical options, rehabilitation protocols, and performance outcomes after operative treatment of articular cartilage defects. Studies have demonstrated improved short- to long-term outcomes in a majority of techniques. However, the clinical benefits of microfracture are short-lived, which has led to the use of alternative procedures. Rehabilitation protocols are not standardized, but emphasis has been placed on bracing, weightbearing, early continuous passive range of motion, and strengthening to improve function. There is growing evidence to suggest that accelerated rehabilitation after matrix-induced autologous chondrocyte implantation may result in superior outcomes compared to delayed rehabilitation. Overall, most techniques result in satisfactory rates of return to play, though existing comparative studies typically include patients with heterogeneous pathology, complicating effective synthesis of outcomes data. In appropriately selected patients, cartilage restoration procedures after articular cartilage injury result in favorable patient-reported clinical outcomes and high rates of return to play. While studies emphasize the critical role that rehabilitation plays with respect to outcomes after surgery, there are substantial inconsistencies in protocols across techniques.

Engineered biochemical cues of regenerative biomaterials to enhance endogenous stem/progenitor cells (ESPCs)-mediated articular cartilage repair.

As a highly specialized shock-absorbing connective tissue, articular cartilage (AC) has very limited self-repair capacity after traumatic injuries, posing a heavy socioeconomic burden. Common clinical therapies for small- to medium-size focal AC defects are well-developed endogenous repair and cell-based strategies, including microfracture, mosaicplasty, autologous chondrocyte implantation (ACI), and matrix-induced ACI (MACI). However, these treatments frequently result in mechanically inferior fibrocartilage, low cost-effectiveness, donor site morbidity, and short-term durability. It prompts an urgent need for innovative approaches to pattern a pro-regenerative microenvironment and yield hyaline-like cartilage with similar biomechanical and biochemical properties as healthy native AC. Acellular regenerative biomaterials can create a favorable local environment for AC repair without causing relevant regulatory and scientific concerns from cell-based treatments. A deeper understanding of the mechanism of endogenous cartilage healing is furthering the (bio)design and application of these scaffolds. Currently, the utilization of regenerative biomaterials to magnify the repairing effect of joint-resident endogenous stem/progenitor cells (ESPCs) presents an evolving improvement for cartilage repair. This review starts by briefly summarizing the current understanding of endogenous AC repair and the vital roles of ESPCs and chemoattractants for cartilage regeneration. Then several intrinsic hurdles for regenerative biomaterials-based AC repair are discussed. The recent advances in novel (bio)design and application regarding regenerative biomaterials with favorable biochemical cues to provide an instructive extracellular microenvironment and to guide the ESPCs (e.g. adhesion, migration, proliferation, differentiation, matrix production, and remodeling) for cartilage repair are summarized. Finally, this review outlines the future directions of engineering the next-generation regenerative biomaterials toward ultimate clinical translation.