Autologous Chondrocyte Implantation Research Articles

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.

Favourable clinical outcomes and low revision rate after M-ACI in adolescents with immature cartilage compared to adult controls: Results at 10 years.

The purpose of this study was to evaluate long-term survival, patient-reported outcomes (PROs)and radiographic results of matrix-associated autologous chondrocyte implantation (M-ACI) in adolescents with immature cartilage and compare them to adult controls. A retrospective matched-pair analysis was performed comparing the PRO after M-ACI for focal cartilage defect of the knee in cartilaginous immature adolescents to mature adults. Groups were matched for sex, body mass index, defect site and size, symptom duration and the number of previous knee surgeries. Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART 2.0) scores were assessed at least 60 months postoperatively. Patient acceptable symptomatic state (PASS) and clinical response rate in KOOS and KOOS subscores were calculated. A total of 54 patients were matched. At a mean of 96 months (65-144 months), no surgical complications, graft hypertrophy or reoperations were noted in the cohorts studied. Adolescents showed superior PROs at the final follow-up (76.9 ± 14.1 vs. 66.4 ± 15.0, p = 0.03) and were significantly more likely to achieve PASS (74.1% vs. 55.6%; p = 0.02) compared to the adult cohort. The KOOS subscale analysis showed long-term benefits for adolescents in terms of symptom improvement, pain reduction, activities of daily living, sports and quality of life (p < 0.05). None of the patients in the adolescent group showed graft hypertrophy on magnet resonance imaging or signs of osteoarthritis on radiographs at long-term follow-ups. M-ACI is an effective treatment for chondral defects of the knee in patients with immature cartilage with low revision rates and high patient satisfaction over the long term. Adolescents showed comparable clinical and radiographic results in the short and medium term, with slightly more favourable, clinically relevant functional results in adolescents in the long term. M-ACI can be safely used in adolescents, and consideration should be given to expanding the indication to include these patients. Level III.

The iPSC secretome is beneficial for in vitro propagation of primary osteoarthritic chondrocytes cell lines

BackgroundOne of the obstacles to autologous chondrocyte implantation (ACI) is obtaining a large quantity of chondrocytes without depletion of their properties. The conditioned medium (CM) from different subpopulations of stem cells (mesenchymal stromal cells (MSC) or induced pluripotent stem cells (iPSC)) could be a gamechanger. MSCs' potential is related to the donor's health and age, which could be omitted when, as a source, iPSCs are used. There is a lack of data regarding their use in the chondrocyte culture expansion. Thus, we wanted to verify whether iPSC-CM could be beneficial for the cell culture of primary chondrocyte cells. MethodsWe added the iPSC-CMs from GPCCi001-A and ND 41658*H cells to the culture of primary chondrocyte cell lines isolated from OA patients (n=6) for other two passages. The composition of the CM was evaluated using Luminex technology. Then, we analysed the senescence, proliferation rate and using flow cytometry: viability, distribution of cell cycle phases, production of reactive oxygen species (ROS) and double-strand breaks. The cartilage-related markers were evaluated using western blot and immunofluorescence. Additionally, a three-dimensional cell culture was used to determine the potential to form cartilage particles. ResultsiPSC-CM increased proliferation and diminished cell ROS production and senescence. CM influenced the cartilage-related protein expression and promoted the growth of cartilage particles. The cell exposed to CM did not lose the ECM proteins, suggesting the chondroprotective effect for prolonged culture time. ConclusionOur preliminary results suggest a beneficial effect on maintaining chondrocyte biology during in vitro expansion.

Clinical Applicability of Autologous Chondrocyte Implantation for the Treatment of Osteochondral Defects: A Meta-analysis.

Osteoarthritis and other joint disorders are the leading cause of disability in the elderly and the treatment of joint lesions is challenging. Autologous chondrocyte implantation (ACI) has been reported with variable effects for the treatment of osteochondral and other joint lesions. In this study, we performed a meta-analysis of the recent literature to determine the clinical applicability of ACI for osteochondral defects. A meta-analysis was performed on the recent literature showing the effects of ACI on osteochondral defects. The PUBMED, ScienceDirect and Google Scholar databases were used to identify eligible studies from Jan 2010 to Sep 2022. Both fixed and random models of meta-analysis were applied with all reported scoring systems to quantify the effectiveness of ACI on osteochondral defects. The pool data of 965 patients as a case series after ACI from a fixed model showed a significant improvement in the osteochondral defects (odds ratio = 8.75, 95%CI = 7.127 to 10.743, p = 0.000). These results were further verified by a random model of meta-analysis. The data also showed a substantial heterogeneity among the studies used in the meta-analysis (Q-value = 160.41, I-squared = 87.53, p = 0.000). Furthermore, this meta-analysis also compared different ACI procedures with different scoring systems but the overall outcome remains the same as ACI was found to be useful for the healing of the osteochondral defects. This meta-analysis of 965 case series revealed that the ACI markedly improved the damage osteochondral defects scores but the optimal treatment is still controversial, therefore further studies are needed to validate these findings in a clinical setting.

The Condition of the Meniscus and Cartilage of the Injured Knee on Preoperative Magnetic Resonance Imaging Is a Prognostic Factor Affecting Postoperative Outcomes Following Knee Cartilage Restoration Surgery

PurposeTo evaluate the relationship between preoperative whole-joint imaging evaluation of the knee with patient reported outcome measures after cartilage restoration surgery (mosaicplasty, osteochondral allograft transplantation (OCA), matrix autologous chondrocyte implantation (MACI)). MethodsWe retrospectively evaluated patients who underwent knee articular cartilage restoration at our institution from 2014 to 2020. The patients’ knee MRI was evaluated with the whole joint magnetic resonance imaging score (WORMS) and semi-quantitative synovial inflammation imaging biomarkers of the preoperative MRI. To assess patient-reported outcome (PRO) score, Lysholm score and Knee Osteoarthritis and Injury Outcome Score (KOOS) were completed at minimum 2 years follow-up. Statistical analysis was performed using Spearman rank test to obtain correlation values for WORMS score and PRO score for each survey. ResultsThere were 40 patients who were enrolled in this study. The average age at baseline was 34.5 years. The average BMI was 28.2 kg/m2 and 26 of 40 were men (range, 20-58 years). The maximum preoperative WORMS score was significantly correlated with the post-operative Lysholm score (r = -0.52, p=0.0013). The WORMS Meniscus and Cartilage sub-scales were significantly correlated with the Lysholm score (r = -0.36, p=0.024 and r = -0.37, p=0.021 respectively). The maximum WORMS score was significantly correlated with the KOOS Daily living and Sports/rec sub-scores (r= -0.47, p=0.0023 and r = -0.42, p=0.0077, respectively). Semi-quantitative synovial inflammation imaging biomarkers were not significantly correlated with PRO scores. ConclusionIncreasing preoperative degenerative change in the knee, as evidenced by a higher WORMS on preoperative MRI, was associated with inferior patient-reported outcomes at a minimum of 2 years after cartilage restoration surgery (mosaicplasty, OCA, MACI). Semi-quantitative scoring of the whole joint on preoperative MRI may allow for improved counseling regarding expected benefit for patients after cartilage restoration surgery.

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.

Treatment of Shoulder Cartilage Defects in Athletes.

Articular cartilage defects in the glenohumeral joint may be found in laborers, the elderly, and young athletes, among others. Various factors can contribute to cartilage damage, including prior surgery, trauma, avascular necrosis, inflammatory arthritis, joint instability, and osteoarthritis. There is a wide variety of treatment options, from conservative treatment, injections, and surgical options, including arthroscopic debridement, microfracture, osteochondral autograft transfer, osteochondral graft transplantation, autologous chondrocyte implantation, and the newly emerging techniques such as biologic augmentation. There is a challenge to determine the optimal treatment options, especially for young athletes, due to limited outcomes in the literature. However, there are many options which are viable to address osteochondral defects of the glenohumeral joint.

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.

Cartilage-Specific Gene Expression and Extracellular Matrix Deposition in the Course of Mesenchymal Stromal Cell Chondrogenic Differentiation in 3D Spheroid Culture.

Articular cartilage damage still remains a major problem in orthopedical surgery. The development of tissue engineering techniques such as autologous chondrocyte implantation is a promising way to improve clinical outcomes. On the other hand, the clinical application of autologous chondrocytes has considerable limitations. Mesenchymal stromal cells (MSCs) from various tissues have been shown to possess chondrogenic differentiation potential, although to different degrees. In the present study, we assessed the alterations in chondrogenesis-related gene transcription rates and extracellular matrix deposition levels before and after the chondrogenic differentiation of MSCs in a 3D spheroid culture. MSCs were obtained from three different tissues: umbilical cord Wharton's jelly (WJMSC-Wharton's jelly mesenchymal stromal cells), adipose tissue (ATMSC-adipose tissue mesenchymal stromal cells), and the dental pulp of deciduous teeth (SHEDs-stem cells from human exfoliated deciduous teeth). Monolayer MSC cultures served as baseline controls. Newly formed 3D spheroids composed of MSCs previously grown in 2D cultures were precultured for 2 days in growth medium, and then, chondrogenic differentiation was induced by maintaining them in the TGF-β1-containing medium for 21 days. Among the MSC types studied, WJMSCs showed the most similarities with primary chondrocytes in terms of the upregulation of cartilage-specific gene expression. Interestingly, such upregulation occurred to some extent in all 3D spheroids, even prior to the addition of TGF-β1. These results confirm that the potential of Wharton's jelly is on par with adipose tissue as a valuable cell source for cartilage engineering applications as well as for the treatment of osteoarthritis. The 3D spheroid environment on its own acts as a trigger for the chondrogenic differentiation of MSCs.

Hydrogel-based and spheroid-based autologous chondrocyte implantation of the knee show similar 2-year functional outcomes: An analysis based on the German Cartilage Registry (KnorpelRegister DGOU).

To compare short-term patient-reported outcomes (PRO) of two contemporary matrix-associated autologous chondrocyte implantation (M-ACI) products for the treatment of large articular cartilage defects of the knee. A retrospective, registry-based, matched-pair analysis was performed, comparing PRO ofpatients undergoing isolated M-ACI with either Spherox™, a spheroid-based ACI (Sb-ACI), or NOVOCART™Inject, a hydrogel-based ACI product (Hb-ACI), for a focal full-thickness cartilage defect of the knee ≥4 cm2. Matching parameters included age, sex, body mass index, defect size, defect localization, symptom duration and previous surgeries. The Knee Injury and Osteoarthritis Outcome Score (KOOS) and the International Knee Documentation Committee (IKDC) score were obtained up to the 24-month follow-up. The total KOOS response rate and percentage of patients attaining a substantial clinical benefit (SCB) in KOOS subscores were calculated. A total of 45 patients per group were matched. The response rate after 24 months was not significantly different between the groups (Sb-ACI 64.4% vs. Hb-ACI 82.2%, p = 0.057). The number of patients with a SCB at 24 months was not significantly different in any KOOS subscore, despite significantly higher improvement of the total KOOS (14.8 ± 16.2 vs. 21.5 ± 15.4, p = 0.047) and KOOS pain in the Hb-ACI group (12.2 ± 18.6 vs. 20.6 ± 19.1, p = 0.037). The IKDC score in the Hb-ACI group was significantly higher at the 12-and 24-month follow-up (60.7 ± 20.2 vs. 70.9 ± 18.0, p = 0.013). The response rate and number of patients achieving an SCB were not significantly different between patients treated with Sb-ACI or Hb-ACI. Both procedures can achieve favourable 2-year PRO. Hb-ACI was associated with better PRO between 1 and 2 years postoperatively;however, the clinical relevance of this benefit is yet to be proven. III, Retrospective comparative study.

Neutral to slightly undercorrected mechanical leg alignment provides superior long-term results in patients undergoing matrix-associated autologous chondrocyte implantation.

The aim of this study was to evaluate the role of leg alignment on long-term clinical outcomeafter matrix-associated autologous chondrocyte implantation (M-ACI) and to define an individualized target range to optimize clinical outcome. The present study examined patients who underwent M-ACI of the femoral condyle. The Knee Injury and Osteoarthritis Outcome Score (KOOS) and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) were used to assess the results. Clinical outcomes were related to Patient Acceptable Symptomatic State (PASS). For intra- and interobserver reliability of mechanical tibiofemoral angle, mechanical medial proximal tibial angleand mechanical lateral distal femoral angle, we calculated intraclass correlation coefficientsusing a two-way mixed model with absolute agreement. A regression model and receiver-operating characteristics curve were used to identify an individual range of alignment where a favourable clinical outcome could be expected in the long term. Additional osteotomy was performed in 50% of patients with similar clinical outcomes as physiologically aligned patients (p > 0.05). The curve-fitting regression model identified a target range of -2.5° valgus to 4.5° varus for ideal postoperative alignment (R2 = 0.12, p = 0.01). Patients within this range were more likely to achieve PASS (70% vs. 27%, p = 0.001). In medially treated defects, a refined range of -2.5° valgus to 4° varus alignment was found (R2 = 0.15, p = 0.01). These patients were more likely to achieve PASS (67% vs. 30%, p = 0.01) and showed favourable postoperative KOOS and MOCART scores (p = 0.02). Patients with lateral defects were more likely to achieve PASS within a range of -2° valgus and 0.5° varus (90% vs. 45%, p = 0.03) and showed favourable postoperative KOOS and MOCART scores (p = not significant). An individual range of leg alignment-whether achieved by osteotomy or physiologic alignment-should be respected in M-ACI treatment. A neutral to slightly undercorrected alignment favours the postoperative outcome after M-ACI. When planning surgery for patients with focal cartilage defects of the femoral condyle, these ranges should be recognized as critical factors. Level III.

Collagen and Alginate Hydrogels Support Chondrocytes Redifferentiation In Vitro without Supplementation of Exogenous Growth Factors.

Focal cartilage defects are a prevalent knee problem affecting people of all ages. Articular cartilage (AC) possesses limited healing potential, and osteochondral defects can lead to pain and long-term complications such as osteoarthritis. Autologous chondrocyte implantation (ACI) has been a successful surgical approach for repairing osteochondral defects over the past two decades. However, a major drawback of ACI is the dedifferentiation of chondrocytes during their in vitro expansion. In this study, we isolated ovine chondrocytes and cultured them in a two-dimensional environment for ACI procedures. We hypothesized that 3D scaffolds would support the cells' redifferentiation without the need for growth factors so we encapsulated them into soft collagen and alginate (col/alg) hydrogels. Chondrocytes embedded into the hydrogels were viable and proliferated. After 7 days, they regained their original rounded morphology (aspect ratio 1.08) and started to aggregate. Gene expression studies showed an upregulation of COL2A1, FOXO3A, FOXO1, ACAN, and COL6A1 (37, 1.13, 22, 1123, and 1.08-fold change expression, respectively) as early as day one. At 21 days, chondrocytes had extensively colonized the hydrogel, forming large cell clusters. They started to replace the degrading scaffold by depositing collagen II and aggrecan, but with limited collagen type I deposition. This approach allows us to overcome the limitations of current approaches such as the dedifferentiation occurring in 2D in vitro expansion and the necrotic formation in spheroids. Further studies are warranted to assess long-term ECM deposition and integration with native cartilage. Though limitations exist, this study suggests a promising avenue for cartilage repair with col/alg hydrogel scaffolds.

Arthroscopic Measurements Predict Knee Chondral Lesion Size More Accurately Than Magnetic Resonance Imaging, and Mechanism of Injury Influences Ability of Either Technique to Predict Graft Size

PurposeTo compare osteochondral defect size measurements and characteristics across magnetic resonance imaging (MRI), arthroscopy, and at the time of implantation with osteochondral allograft (OCA) transplantation or autologous chondrocyte implantation (ACI). MethodsPatients who underwent ACI and OCA transplantation at a single institution between 2015 and 2019 were retrospectively identified. Patients were excluded if they had severe osteoarthritis, if MRIs were not available for review, if surgical records did not include defect sizing necessary for analysis, and if operative reports were not available. Osteochondral lesion characteristics including size were collected preoperatively from MRI and arthroscopy and at the time of definitive open surgical intervention. Subgroup analysis was performed comparing measurement techniques depending on the corrective surgical approach used as well as depending on the mechanism of chondral injury to determine if these had any effect on the ability of arthroscopy or MRI to predict graft size. ResultsOverall, 136 chondral lesions were addressed with restoration procedures in 117 patients (mean age 32.5 years). Average difference between final graft size and lesion area measured with index arthroscopy was 116 mm2, while average difference between final graft size and lesion size measured with preoperative MRI was 182 mm2 (P < .001). Depending on surgical technique, measurements with MRI were more similar to final graft size when a patient underwent OCA transplantation versus ACI (P = .007). Depending on mechanism of injury, MRI measurements of lesions were closer to graft area when lesions resulted from trauma (P = .047). ConclusionChondral lesion size determined by preoperative MRI imaging is less accurate than arthroscopic measurements. The mechanism injury leading to chondral damage and degree of damage may influence the ability of MRI and arthroscopy to accurately measure chondral lesions and predict the final graft size used in surgical correction. Level of EvidenceRetrospective Cohort Study (Level III)

A RANDOMIZED CONTROLLED TRIAL EVALUATING AN ACCELERATED WEIGHT-BEARING REHABILITATION PATHWAY AFTER MATRIX-INDUCED AUTOLOGOUS CHONDROCYTE IMPLANTATION FOR SYMPTOMATIC KNEE CARTILAGE DEFECTS

INTRODUCTION &amp; AIMS Matrix-induced autologous chondrocyte implantation (MACI) has demonstrated encouraging outcomes in treating symptomatic knee cartilage lesions which, if untreated, can progress toward early osteoarthritis. Rehabilitation is imperative to optimize outcome, though has been traditionally conservative. This study investigated the long-term outcomes of an accelerated return to full weight bearing (WB) after MACI. METHODS This prospective randomized controlled trial (RCT) allocated 35 patients (37 knees) to a 6-week (n=18) or 8-week (n=19) return to full WB after MACI. Patients were evaluated pre-operatively and at 1, 2, 5 and ≥10 years, via patient-reported outcome measures (PROMs) including the Knee Osteoarthritis Outcome Score (KOOS). Single limb hop capacity and peak knee extensor and flexor torque were assessed, with limb symmetry indices (LSIs) calculated. Magnetic resonance imaging (MRI) evaluated repair tissue, while a validated MRI composite graft score was calculated. RESULTS While the 6-week WB group reported significantly better 1-year KOOS Quality of Life scores, no other differences (p&amp;gt;0.05) in PROMs existed. The peak knee extensor torque LSI significantly improved (p&amp;lt;0.0001) over time, with mean LSIs of 100.8 (6-week) and 99.1 (8-week) at ≥10 years. No group differences (p&amp;gt;0.05) were observed in hop LSIs. A non-significant decline (p&amp;gt;0.05) was observed for the MRI composite score from 1-year to final ≥10-year review and, apart from a significant group effect (p=0.028) for graft tissue intensity in favor of the 6-week group suggesting repair tissue more reflective of native cartilage, no other MRI-based differences (p&amp;gt;0.05) existed. At ≥10-years, no grafts on MRI had failed, though 3 patients (6-week n=1, 8-week n=2) had progressed toward knee arthroplasty. CONCLUSION The 6-week accelerated rehabilitation program provided comparable clinical and MRI-based outcomes beyond 10 years post-surgery, without jeopardizing the graft.

Do reconstructive techniques for osteochondritis dissecans of the skeletally mature knee work?A systematic review and meta-analysis.

Osteochondritis dissecans (OCD) is a common cause of knee pain. Management for adult-onset OCD (AOCD) usually involves surgery. Surgical treatments include palliative, reparative and reconstructive techniques. The aim of this systematic review and meta-analysis is to evaluate the efficacy of reconstructive techniques for the treatment of OCD in skeletally mature knees. A systematic search was carried out on four databases up to November 2023 (Medline, Embase, Cochrane Library, Web of Science). The study was registered on international prospective register of systematic reviews and performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Clinical studies on skeletally mature patients were included, which utilised reconstructive techniques such as autologous chondrocyte implantation (ACI), matrix-induced autologous chondrocyte implantation, osteochondral allograft transplantation surgeryor bone marrow-derived cellular transplantation. Demographical data, patient-reported outcome measures and postoperative complications were recorded. Quantitative outcome measures that were comparable across studies were pooled for meta-analysis. A random effects model was used. Heterogeneity was assessed using the I2 statistic and Cochran's Q test. Statistical significance was set at p < 0.05. Risk of bias was assessed using the risk of bias in non-randomised studies - of interventions tool for nonrandomised studies. Sixteen studies were included with 458 OCD lesions in 432 patients. The average age was 24.9, and 62.6% were male. The mean follow-up time was 61.5 months. At 36 months follow-up, International Knee Documentation Committee (IKDC) subjective, Tegner and EuroQol-visual analogue scale (EQ-VAS) scores improved from 42.4 to 78.6 (standard mean difference [SMD]: 2.47; p < 0.001), 2.27-4.99 (SMD: 2.363; p = 0.002) and 30.4-57.5 (SMD: 2.390; p < 0.001), respectively. Overall complication rate was 8.9%. Smaller OCD lesion sizes resulted in a greater improvement in IKDC subjective (SMD: 2.64 vs. 2.01; p = 0.038), EQ-VAS (SMD: 3.16 vs. 0.95; p = 0.046) and Tegner scores (SMD: 3.13 vs. 1.05; p = 0.007) and had a lower complication rate (p = 0.008). Males showed a larger improvement in IKDC subjective scores than females (SMD: 2.56 vs. 1.56; p = 0.029), while younger patients had a larger improvement in IKDC subjective scores (SMD: 2.71 vs. 2.12; p = 0.045) and fewer complications than older patients (p = 0.003). There were no significant differences between cohorts treated with ACI and those treated with non-ACI reconstructive techniques. Publication bias was not detected (n.s.). Reconstructive techniques used to treat OCD in the skeletally mature knee resulted in significant improvements in clinical and functional outcomes, with a low overall complication rate. Since a younger age leads to a greater improvement in IKDC subjective score and a lower complication rate, surgical intervention should not be delayed, especially in AOCD lesions which are more likely to follow a progressive and unremitting clinical course. Level III.

Comparative study on clinical outcomes in autologous chondrocyte implantation using three-dimensional cultured JACC® with collagen versus periosteum coverings.

This study investigates the efficacy of a collagen membrane as a substitute for autologous periosteum in atelocollagen-assisted autologous chondrocyte implantation (ACI) using J-TEC autologous cultured cartilage (JACC®). Sixty-nine patients with knee joint chondral defects underwent ACI using JACC®-34 with periosteum-covered ACI (P-ACIs) and 35 with collagen-covered ACI (C-ACIs). Clinical outcomes were compared through patient-reported measures, International Cartilage Repair Society (ICRS) Cartilage Repair Assessment (CRA) scores at second-look arthroscopy one year postoperatively, and adverse event incidence. Postoperative subjective scores significantly improved up to two years, with no significant differences between P-ACI and C-ACI groups. However, C-ACI exhibited a lower adverse event rate (p = 0.034) and significantly higher ICRS CRA scores (p = 0.0001). Notably, C-ACI outperformed P-ACI in both femoral condyle and trochlea assessments (p = 0.0157 and 0.0005, respectively). While clinical outcomes were comparable, the use of a collagen membrane demonstrated superiority in ICRS CRA during second-look arthroscopy and adverse event occurrence.

Knee Cartilage Injuries in Football Players: Clinical Outcomes and Return to Sport After Surgical Treatment: A Systematic Review of the Literature.

To systematically review the literature and analyze clinical outcomes and return-to-sport after surgical management of cartilage injuries in football players. A systematic literature review was performed in August 2023 on PubMed, WebOfScience, and Cochrane Library to collect studies on surgical strategies for cartilage lesions in football players. Methodological quality and risk of bias were assessed with the modified Coleman Methodology score and RoB2 and RoBANS2 tools. Fifteen studies on 409 football players (86% men, 14% women) were included: nine prospective and two retrospective case series, one randomized controlled trial, one prospective comparative study, one case report, and one survey. Bone marrow stimulation (BMS) techniques were the most documented. The lesion size influenced the treatment choice: debridement was used for small lesions (1.1 cm2), BMS, osteochondral autograft transplantation (OAT), matrix-assisted autologous chondrocytes transplantation (MACT), and scaffold-augmented BMS for small/mid-size lesions (2.2-3.0 cm2), and autologous chondrocytes implantation (ACI) for larger lesions (5.8 cm2). The surgical options yielded different results in terms of clinical outcome and return-to-sport, with fastest recovery for debridement and scaffold-augmented BMS. The current evidence is limited with large methodological quality variation (modified Coleman Methodology score 43.5/100) and a high risk of bias. Decision-making in cartilage injuries seems to privilege early return-to-sport, making debridement and microfractures the most used techniques. The lesion size influences the treatment choice. However, the current evidence is limited. Further studies are needed to confirm these findings and establish a case-based approach to treat cartilage injuries in football players based on the specific patient and lesion characteristics and the treatments' potential in terms of both return-to-sport and long-term results. Systematic review, level IV.

Intermediate-Term Clinical Outcomes of High-Density Autologous Chondrocyte Implantation in Patients with Concomitant Anterior Cruciate Ligament Reconstruction and Focal Chondral Lesions.

To investigate intermediate-term clinical results in patients with concomitant anterior cruciate ligament (ACL) reconstruction and chondral defect treated with high-density autologous chondrocyte implantation (HD-ACI) compared to patients without ACL tear but with a chondral lesion and HD-ACI treatment. Forty-eight patients with focal chondral lesions underwent HD-ACI (24 with ACL reconstruction after an ACL injury and 24 with an intact ACL). Follow-up assessments occurred at 6, 12, and 24 months. Patient-reported knee function and symptoms were assessed using the International Knee Documentation Committee (IKDC) questionnaire, pain was measured using the Visual Analog Scale (VAS), and adverse events were monitored. Physical activity was assessed using the Tegner Activity Level Scale, and cartilage healing was evaluated with the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. No significant adverse events occurred during follow-up. Both groups showed significant improvements at 2 years compared to baseline (VAS: 8.0 ± 1.3 to 1.4 ± 2.0 [normal ACL]; 7.4 ± 2.3 to 2.1 ± 2.3 [ACL reconstruction]; IKDC: 39.2 ± 10.6 to 76.1 ± 22.0 [intact ACL]; 35.6 ± 12.1 to 74.6 ± 20.9 [ACL reconstruction]). Patients in both groups exceeded the minimal clinically important difference (MCID) for IKDC scores. The Tegner Activity Level Scale decreased immediately after surgery and increased after 2 years, with 70.6% (normal ACL) and 89.5% (ACL reconstruction) returning to their preinjury activity levels. No significant differences in the MOCART score were observed between the groups. ACL reconstruction does not appear to reduce the outcomes (at 2 years) of HD-ACI.

Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) Scores > 55 at 6 Months Postoperative Predict Ability to Achieve Patient Acceptable Symptomatic State at Minimum 1 Year Postoperative Following Autologous Chondrocyte Implantation for Grade IV Chondral Defects About the Patellofemoral Joint.

The primary aim is to evaluate the relationship between MOCART scores and patient satisfaction, as evaluated by achievement of (1) the Patient Acceptable Symptomatic State (PASS) and (2) the minimal clinically important difference (MCID) for Knee Injury and Osteoarthritis Score Quality of Life (KOOS QoL), for patients undergoing autologous chondrocyte implantation (ACI) for focal Grade IV patellofemoral chondral defects. The secondary aim is to determine the threshold MOCART score which predicts the ability to meet the PASS and the MCID for KOOS QoL. Patients undergoing ACI for grade IV patellofemoral chondral defects by a single surgeon from 2017 to 2020 were identified by search of the EMR. To determine PASS status, patients were asked, "Do you consider your current level of symptoms to be acceptable?" KOOS QoL scores were also collected. Patients with 6-month postoperative knee MRI, PASS scores, and minimum 2-year follow-up data were included. Paired t tests and Wilcoxon Rank-Sum tests were used to evaluate the relationship between MOCART scores and (1) PASS achievement and (2) achievement of the MCID for KOOS QoL (12.8). Thirty-four patients were included, with a median age of 35.1 years [IQR: 24.6, 37.1], and BMI of 24.0 kg/m2 [IQR: 21.5, 28.1]. The median time to postoperative MRI was 6.7 months [IQR: 5.8, 7.9], and average follow-up time was 3.7 ± 1.2 years. Twenty-five patients (74%) achieved PASS, and 18 patients (out of 27 who had postop KOOS QoL Scores, 67%) achieved the MCID for KOOS QoL. Patients who achieved PASS had higher average MOCART scores (61.8 ± 16.0) than those who did not achieve PASS (45.0 ± 12.8, p=0.011), whereas patients who achieved the MCID for KOOS QoL did not have higher MOCART scores than those who did not achieve the MCID (61.9 ± 18.3 versus 53.3 ± 17.1, P = 0.25). There was no relationship between age, sex, lesion size, and lesion location and ability to achieve PASS or MCID for KOOS QoL (p>0.05). A threshold MOCART value of 55 was associated with the highest AUC on ROC analysis for likelihood of achieving PASS (0.778) and MCID for KOOS QoL (0.667). Higher MOCART scores are associated with an increased likelihood of achieving PASS following patellofemoral ACI. Moreover, MOCART scores > 55 predict the ability to achieve PASS and the MCID for KOOS QoL following patellofemoral ACI. IV.

Autologous Chondrocyte Implantation for the Treatment of Osteochondral Lesions of the Talus: What Happens after 20 Years?

The purpose of this study was to assess the long-term clinical efficacy of first-generation autologous chondrocyte implantation (ACI) technique for osteochondral lesions of the ankle joint. Eleven patients with symptomatic OLTs underwent ACI from December 1997 to October 2002. A total of 9 patients (5 men, 4 women, age 25.2±6.3) were evaluated at baseline and at 1, 3, 10 years, and at final follow-up of minimum 20 years with AOFAS ankle-hindfoot score, NRS for pain, and with the Tegner score. The AOFAS score improved significantly from the baseline value of 40.4±19.8 to 82.7±12.9 at the final follow-up (p<0.0005). The NRS for pain improved significantly from 7.8±0.7 at baseline to 4.8±2.1 at the final follow-up (p<0.0005). Moreover, the Tegner score underwent a modification from the pre-operative median value of 1 (range: 1-3) and from a pre-injury value of 5 (range: 3-7) to 3 (range: 2-4) at the final follow-up (p<0.0005). ACI has proven to be an effective treatment option for patients suffering from OLTs, leading to a long-lasting clinical improvement even beyond 20 years of follow-up. Level IV.