MR imaging after patellar MACI and MPFL reconstruction: a comparison of isolated versus combined procedures.

OBJECTIVE: To qualitatively and quantitatively evaluate the 2.5-year MRI outcome after Matrix-associated autologous chondrocyte implantation (MACI) at the patella, reconstruction of the medial patellofemoral ligament (MPFL), and combined procedures. METHODS: In 66 consecutive patients (age 22.8 ± 6.4years) with MACI at the patella (n = 16), MPFL reconstruction (MPFL; n = 31), or combined procedures (n = 19) 3T MRI was performed 2.5 years after surgery. For morphological MRI evaluation WORMS and MOCART scores were obtained. In addition quantitative cartilage T2 and T1rho relaxation times were acquired. Several clinical scores were obtained. Statistical analyses included descriptive statistics, Mann-Whitney-U-tests and Pearson correlations. RESULTS: WORMS scores at follow-up (FU) were significantly worse after combined procedures (8.7 ± 4.9) than after isolated MACI (4.3 ± 3.6, P = 0.005) and after isolated MPFL reconstruction (5.3 ± 5.7, P = 0.004). Bone marrow edema at the patella in the combined group was the only (non-significantly) worsening WORMS parameter from pre- to postoperatively. MOCART scores were significantly worse in the combined group than in the isolated MACI group (57 ± 3 vs 88 ± 9, P < 0.001). Perfect defect filling was achieved in 26% and 69% of cases in the combined and MACI group, respectively (P = 0.031). Global and patellar T2 values were higher in the combined group (Global T2: 34.0 ± 2.8ms) and MACI group (35.5 ± 3.1ms) as compared to the MPFL group (31.1 ± 3.2ms, P < 0.05). T2 values correlated significantly with clinical scores (P < 0.005). Clinical Cincinnati scores were significantly worse in the combined group (P < 0.05). CONCLUSION: After combined surgery with patellar MACI and MPFL reconstruction inferior MRI outcomes were observed than after isolated procedures. Therefore, patients with need for combined surgery may be at particular risk for osteoarthritis.

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

PURPOSE: 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. METHODS: 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 surgery or 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. RESULTS: 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.). CONCLUSION: 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 OF EVIDENCE: Level III.

The role of autologous bone grafting in matrix-associated autologous chondrocyte implantation at the knee: Results from the German Cartilage Registry (KnorpelRegister DGOU).

PURPOSE: To investigate whether concomitant autologous bone grafting adversely affects clinical outcome and graft survival after matrix-associated autologous chondrocyte implantation (M-ACI). METHODS: The present study examines registry data of patients who underwent M-ACI with or without autologous bone grafting for large-sized chondral or osteochondral defects. Propensity score matching was performed to exclude potential confounders. A total of 215 patients with similar baseline characteristics were identified. Clinical outcome was assessed at the time of surgery and at 6, 12, 24, 36 and 60 months using the Knee Injury and Osteoarthritis Outcome Score (KOOS). KOOS change, clinical response rate, KOOS subcomponents and failure rate were determined. RESULTS: Patients treated with M-ACI and autologous bone grafting achieved comparable clinical outcomes compared with M-ACI alone. At 24 months postoperatively, the patient-reported outcome (PRO) of patients treated with M-ACI and autologous bone grafting was even significantly better as measured by KOOS (74.9 ± 18.8 vs. 79.2 ± 15.4; p = 0.043). However, the difference did not exceed the minimal clinically important difference (MCID). In patients with M-ACI and autologous bone grafting, a greater change in KOOS relative to baseline was observed at 6 (9.3 ± 14.7 vs. 15.0 ± 14.7; p = 0.004) and 12 months (12.6 ± 17.2 vs. 17.7 ± 14.6; p = 0.035). Overall, a high clinical response rate was observed in both groups at 24 months (75.8% vs. 82.0%; p = n.s.). The estimated survival at the endpoint of reoperation for any reason was 82.1% (SD 2.8) at 8.4 years for isolated M-ACI and 88.7% (SD 2.4) at 8.2 years for M-ACI with autologous bone grafting (p = 0.039). CONCLUSIONS: Even in the challenging cohort of large osteochondral defects, the additional treatment with autologous bone grafting leads to remarkably good clinical outcomes in patients treated with M-ACI. In fact, they tend to benefit more from surgery, have lower revision rates and achieve clinical response rates earlier. Subchondral bone management is critical to the success of M-ACI and should be addressed in the treatment of borderline defects. LEVEL OF EVIDENCE: Level III.

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

PURPOSE: The aim of this study was to evaluate the role of leg alignment on long-term clinical outcome after matrix-associated autologous chondrocyte implantation (M-ACI) and to define an individualized target range to optimize clinical outcome. METHODS: 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 angle and mechanical lateral distal femoral angle, we calculated intraclass correlation coefficients using 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. RESULTS: 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). CONCLUSIONS: 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 OF EVIDENCE: Level III.

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).

PURPOSE: 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. METHODS: A retrospective, registry-based, matched-pair analysis was performed, comparing PRO of patients 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. RESULTS: 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). CONCLUSION: 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. LEVEL OF EVIDENCE: III, Retrospective comparative study.

Sex does not influence the long-term outcome of matrix-assisted autologous chondrocyte transplantation.

PURPOSE: Regenerative techniques for articular cartilage lesions demonstrated heterogeneous clinical results. Several factors may influence the outcome, with sex being one of the most debated. This study aimed at quantifying the long-term influence of sex on the clinical outcome obtained with a regenerative procedure for knee chondral lesions. METHODS: Matrix-assisted autologous chondrocyte transplantation (MACT) was used to treat 235 knees which were prospectively evaluated with the International Knee Documentation Committee (IKDC), EuroQol visual analogue scale, and Tegner scores at 14-year mean follow-up. A multilevel analysis was performed with the IKDC subjective scores standardised according to the age/sex category of each patient and/or the selection of a match-paired subgroup to compare homogeneous men and women patients. RESULTS: At 14 years, men and women showed a failure rate of 10.7% and 28.8%, respectively (p < 0.0005). An overall improvement was observed in both sexes. Women had more patellar lesions and men more condylar lesions (p = 0.001), and the latter also presented a higher preinjury activity level (p < 0.0005). Men had significantly higher IKDC subjective scores at all follow-ups (at 14 years: 77.2 ± 18.9 vs. 62.8 ± 23.1; p < 0.0005). However, the analysis of homogeneous match-paired populations of men and women, with standardised IKDC subjective scores, showed no differences between men and women (at 14 years: -1.6 ± 1.7 vs. -1.9 ± 1.6). CONCLUSION: Men and women treated with MACT for knee chondral lesions presented a significant improvement and stable long-term results. When both sexes are compared with homogeneous match-paired groups, they have similar results over time. However, women present more often unfavourable lesion patterns, which proved more challenging in terms of long-term outcome after MACT. LEVEL OF EVIDENCE: Level II.

Significant improvements in clinical outcome measures and patient satisfaction after combined all-arthroscopic meniscal allograft transplantation and autologous chondrocyte implantation: A single-centre longitudinal study.

PURPOSE: The optimal treatment approach for the complex pathology of meniscal insufficiency and coexisting full-thickness cartilage defects remains unclear. The purpose of this study was to evaluate the viability, safety, and efficacy of this combined surgical approach at medium-term follow-up. METHODS: This is a single-centre longitudinal study with blinded outcome assessment. All consecutive patients treated with combined all-arthroscopic meniscal allograft transplantation (MAT) with bone bridge fixation and ACI using chondrospheres at our institution between 2001 and 2021 were eligible for inclusion. Twenty patients with an average follow-up of 72.6 ± 34.4 months were included in the statistical analysis. Clinical outcomes were assessed pre- and postoperatively using the IKDC Subjective Knee Form, Lysholm Score, Tegner Activity Scale, KOOS, and Visual Analog Scale (VAS) for patient satisfaction. Failure and reoperation rates were assessed, and cartilage regeneration tissue was evaluated on postoperative MRI. RESULTS: IKDC scores significantly improved from 52.1 ± 16.9 to 68.5 ± 16.3 (p = 0.003). Lysholm scores improved from 61.5 ± 21.7 to 78.5 ± 12.9 (p = 0.004). Tegner scores improved from 3.5 (1-4) to 4.0 (2-6) (p = 0.014). KOOS scores improved significantly across all subcategories, except 'symptoms', where improvements did not reach statistical significance. VAS for overall patient satisfaction showed improvements but did not reach statistical significance. The combined procedure was successful in 17 patients (85%). Eight patients had to undergo reoperation (40%), comprising mostly small, arthroscopic procedures. Seven reoperations were directly attributable to meniscal allograft transplantation (46.7%). Postoperative Magnetic Resonance Observation of Cartilage Repair Tissue scores were 68.9 ± 16.8 (n = 14). CONCLUSION: Combined arthroscopic MAT and autologous chondrocyte implantation (ACI) is a viable, safe, and effective treatment approach for younger patients with meniscal insufficiency and coexisting full-thickness cartilage damage, where alternative treatment options are limited. The combined surgical procedure achieved significant improvements in clinical outcome measures and patient satisfaction with acceptable failure and high arthroscopic reoperation rates. MAT is the limiting part of this combined procedure, with most failures and reoperations being attributable to MAT, as opposed to ACI. LEVEL OF EVIDENCE: Level III.

Total meniscus replacement with a 3D printing of network hydrogel composite scaffold in a rabbit model.

PURPOSE: The aim of this study was to evaluate the role of a novel total meniscal implant in promoting meniscal regeneration and protecting articular cartilage in a rabbit model for 3 and 6 months. METHODS: Thirty-six New Zealand rabbits were selected and divided into poly(ɛ-caprolactone) (PG-Pg) scaffold group, meniscectomy group and sham group. In this study, it was investigated whether PG-Pg scaffold can prevent articular cartilage degeneration and promote tissue degeneration, and its mechanical properties at 3 and 6 months after surgery were also explored. RESULT: The degree of articular cartilage degeneration was significantly lower in the PG-Pg scaffold group than in the meniscectomy group. The number of chondrocytes increased in the PG-Pg scaffold at 3 and 6 months, while a gradual increase in the mechanical properties of the PG-Pg stent was observed from 6 months. CONCLUSION: The PG-Pg scaffold slows down the degeneration of articular cartilage, promotes tissue regeneration and improves biomechanical properties after meniscectomy. This novel meniscus scaffold holds promise for enhancing surgical strategies and delivering superior long-term results for individuals with severe meniscus tears. LEVEL OF EVIDENCE: NA.

The regenerative treatment of costal osteochondral graft implantation for partial growth arrest using a rabbit model.

PURPOSE: To investigate the feasibility of cylindrical costal osteochondral graft transplantation as a novel regenerative treatment in growth arrest. METHODS: The medial portion of the proximal tibial growth plate of 6-week-old male New Zealand White rabbits was resected to establish an experimental model of partial growth plate injury. The rabbits were divided into four groups: no-treatment, bone wax transplantation, costal chondral graft, and costal osteochondral graft groups. Radiographic and micro-computed tomography scan results were analyzed to evaluate angular deformity of the tibia and bony bridge formation at the injury site. In addition, repair of the injured growth plate cartilage was assessed histologically at 4, 8, and 12 weeks postoperatively. RESULTS: Radiographic examination revealed that bone wax transplantation continuously decreased the medial proximal tibial angle (MPTA) while the costal chondral graft implantation reduced the decrease of MPTA at 12 weeks postoperatively. The costal osteochondral graft implantation recovered the MPTA, close to the normal. Histologically, the costal osteochondral grafts retained the MPTA in the injured site compared to costal chondral grafts. Additionally, hypertrophic chondrocytes were observed at the graft site in the costal osteochondral graft group at 12 weeks, suggesting that endochondral ossification may occur at the graft site similar to normal ossification. The fluorescence in situ hybridization analysis of osteochondral grafts transplanted from male to female rabbits indicated that they were replaced by cells of host origin. CONCLUSION: The costal osteochondral graft can achieve regeneration without bony bridge formation in partial growth plate injury.

Atelocollagen-associated autologous chondrocyte implantation for the repair of large cartilage defects of the knee: Results at three to seven years.

BACKGROUND: Recently, various types of engineered autologous chondrocyte implantation (ACI) have been developed. Atelocollagen-associated ACI (A-ACI) is the only ACI procedure covered by Japanese Health Insurance since 2013. The indications of the A-ACI are traumatic cartilage defects and osteochondral dissecans (OCD) for knee joints. PURPOSE: To evaluate midterm clinical results after A-ACI for the treatment for full-thickness cartilage defects of the knee. METHODS: Thirteen consecutive patients who underwent A-ACI between 2014 and 2018 had been prospectively enrolled in this study. There were 11 men and 2 women with a mean age of 34 years at the time of surgery. The causes of the cartilage defect were trauma in 10 knees and OCD in 3 knees. The total number of lesions was 15, which were comprised of the medial femoral condyle in 5 knees, the lateral femoral condyle in 5 knees, and the femoral trochlea in 5 knees. The mean size of the lesion was 5.3 cm2. Each knee was clinically and radiologically evaluated preoperatively and postoperatively. RESULTS: The mean Lysholm score improved significantly from 74.0 points to 94.0 points (p = 0.008) and each subscale in Knee injury and Osteoarthritis Outcome Score improved significantly (p < 0.001) at the mean final follow-up period of 51 months (range, 36-84 months). The magnetic resonance observation of cartilage repair tissue 2.0 score at the mean follow-up of 38 months was significantly higher than that at 2 months postoperatively (p = 0.014). According to the International Cartilage Repair Society (ICRS) grading scale, 3 knees were graded as normal, 3 knees as nearly normal, and 1 knee as severely abnormal in second-look arthroscopic evaluation at a mean of 22 months (range, 8-41 months) after A-ACI. CONCLUSION: The present study showed a significant subjective and objective clinical improvement in the A-ACI for large cartilage defects of the knee at a mean follow-up of 51 months (range, 36-84 months).

A regenerative approach for temporomandibular joint repair: An in vitro and ex vivo study.

BACKGROUND: Current clinical approaches to regenerate temporomandibular joint (TMJ) articulating cartilage defects only treat the symptoms (i.e. pain and dysfunction) and do not seek to restore joint integrity for long-term relief. Therefore, we investigated a novel self-assembling tissue-engineered cartilage to overcome this significant clinical issue for TMJ regenerative purposes. OBJECTIVES: Examine the maturation of dynamic self-regenerating cartilage (dSRC) using auricular chondrocytes and evaluate a novel combinatorial approach with fractional laser treatment and dSRC implantation for TMJ cartilage repair. MATERIALS AND METHODS: A suspension of 107 freshly harvested rabbit ear chondrocytes was cultured under a continuous reciprocating motion to form the dSRC. After 2, 4 and 8 weeks of culture, dSRC samples were stained with H&E, Safranin-O and Toluidine Blue. Immunohistochemistry (IHC) was performed for collagens type I and II. Channels (300-500 µm diameter and 1.2-1.5 mm depth) were created in six freshly harvested condyles using a fractional Erbium laser. Two groups were tested: dSRC in a laser-ablated lesion (experimental) and an empty laser-ablated channel (control). TMJ condyles were cultured for up to 8 weeks and analysed as described above. RESULTS: H&E staining showed a high cell density in dSRC compared to native cartilage. All dSRC groups demonstrated intense Safranin-O staining, indicating high glycosaminoglycan (GAG) production and intense Toluidine Blue staining showed high proteoglycan content. IHC confirmed that dSRC consisted predominantly of collagen type II. The experimental group showed improved cartilage repair at both time points compared to the empty channels. CONCLUSION: dSRC viability and successful matrix formation were demonstrated in vitro. The combination of fractional laser ablation and dSRC implantation enhanced cartilage repair.

Autologous chondrocyte implantation for the treatment of osteochondral lesions of the talus: What happens after 20 years?

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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 OF EVIDENCE: Level IV.

A randomized controlled trial demonstrating sustained benefit of autologous matrix-induced chondrogenesis (AMIC®) over microfracture: 10-year follow-up.

PURPOSE: Autologous matrix-induced chondrogenesis (AMIC®) and microfracture are established treatments for focal chondral defects in the knee, but there are little clinical data concerning these procedures over the long term. This study evaluates the outcomes of AMIC® compared to microfracture over 10-year follow-up. METHODS: Forty-seven patients were randomized and treated either with MFx (n = 13), sutured AMIC® (n = 17) or glued AMIC® (n = 17) in a prospective, randomized, controlled multicentre trial. The Modified Cincinnati Knee Score, a visual analogue scale for pain and MOCART score were used to assess outcomes over 10 years post-operatively. RESULTS: All treatment arms improved in the first 2 years, but a progressive and significant deterioration in scores was observed in the MFx group, while both AMIC® groups remained stable. MOCART scores were comparable between groups. CONCLUSION: The AMIC® procedure results in improved patient outcomes in comparison with microfracture up to 10 years following surgery for the repair of focal chondral defects in the knee. CLINICALTRIALS: gov Identifier: NCT02993510.

Particulate cartilage and platelet-rich plasma treatment for knee chondral defects in sheep.

PURPOSE: Articular cartilage is vulnerable to multiple types of damage and it has limited reparative and regenerative capacities due to its absence of vascularity. Although a large number of therapeutic strategies exist to treat chondral defects, they have some limitations, such as fibrocartilage formation. Therefore, the goal of the present study was to evaluate the chondrogenic regenerative properties of an autologous-made matrix of particulated cartilage and platelet-rich plasma (PACI + PRP) implantation for the treatment of full-thickness chondral defects in sheep. METHODS: A full-thickness 8 mm diameter cartilage defect was created in the weight-bearing area of the medial femoral condyle in both knees of 16 sheep. The right knees of all animals were treated with particulated autograft cartilage implantation and platelet-rich plasma, while the left knees were injected with Ringer's lactate solution or hyaluronic acid. The sheep were killed 9 or 18 months after surgery. Macroscopic evaluations were performed using three different scoring systems, and histopathological evaluations were performed using a modified scoring system based on different scoring systems. RESULTS: The PACI + PRP groups showed statistically significant differences in the percentage of defect repair and chondrocytes in the newly formed cartilage tissue at 18 months compared to 9 months. CONCLUSIONS: The results suggest that macroscopic appearance, histological structure and chondrocyte repair were improved when using PACI + PRP treatment for chondral defects, producing an outcome similar to the surrounding healthy cartilage. PACI + PRP is a totally autologous, easy, and unexpensive treatment that can be performed in one-step procedure and is useful as a therapeutic option for knee chondral defects.

Autologous chondrocyte implantation in the knee is effective in skeletally immature patients: a systematic review.

PURPOSE: This systematic review evaluated the efficacy and safety of autologous chondrocyte implantation (ACI) for chondral defects of the knee in skeletally immature patients. Current available data from patients reported outcome measures (PROMs) and complications were collected, analyzed, and discussed. METHODS: This systematic review was conducted according to the PRISMA guidelines. The following databases were accessed in May 2022: PubMed, Google scholar, Embase, and Scopus. All the clinical studies investigating the efficacy of ACI to manage chondral defects of the knee in skeletally immature patients were accessed. Articles treating patients with surgical procedures other than ACI were not eligible, nor were studies with a follow-up shorter than 12 months. RESULTS: Data from 9 studies (251 procedures) were collected. 32% (80 of 251) of patients were females. The mean length of follow-up was 44.2 ± 29.4 (range, 12-115) months. The mean age of the patients was 16.4 ± 0.7 (range, 15-17) years. The Knee injury and Osteoarthritis Outcome Score (KOOS) and International Knee Document Committee (IKDC) increased of + 41.9/100 (P = 0.003) and + 33.2/100 (P = < 0.0001) points, respectively. The Lysholm Knee Score improved of + 20.6/100 (P = 0.02) points. The Visual Analogue Scale (VAS) for pain reduced of - 3.6/10 (P = 0.004) points. The Tegner scale did not show any statistically significant improvement from baseline to follow-up (P = n.s.). The rate of graft hypertrophy was 12.5% (5 of 40 patients), and the rate of failure 5.6% (8 of 142 patients). CONCLUSION: ACI for chondral defects of the knee is effective to improve PROMs in skeletally immature patients. The safety profile of ACI still remains controversial. LEVEL OF EVIDENCE: III.

Autologous chondrocyte implantation provides good long-term clinical results in the treatment of knee osteoarthritis: a systematic review.

PURPOSE: To evaluate the mid- and long-term efficacy of autologous chondrocyte implantation (ACI) and matrix-assisted chondrocyte implantation (MACI) to treat patients with knee cartilage defects in the presence of osteoarthritis (OA). METHODS: PubMed and Cochrane databases were systematically searched for studies describing the treatment of knee OA with ACI or MACI (Kellgren-Lawrence (KL) ≥ 1, minimum follow-up 36 months). Results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines and included Lysholm, Western Ontario McMaster University and International Knee Documentation Committee scores. RESULTS: Of the 127 full-text articles assessed for eligibility, only five studies were selected based on inclusion/exclusion criteria (2 on ACI and 3 on MACI). In both groups, the defects were mainly located at femoral level, size 2.2-15.1 cm2 in the ACI and 2.0-7.6 cm2 in the MACI group. ACI was mostly used for patients affected by KL I, whereas MACI for patients with KL II-IV. The data obtained from 235 patients (161 ACI, 74 MACI) showed that ACI and MACI sustained stable clinical improvements up to 11 and 15 years, respectively, with a failure rate of about 10% up to 11 years. Scarce biological details regarding chondrocyte implantation were reported. CONCLUSIONS: ACI and MACI procedures for the treatment of knee cartilage lesions associated to OA showed long-term success and allowed delaying arthroplasty. Additional trials reporting homogenous data and precise patient characterization are needed to conduct an effective literature meta-analysis and identify the clinical relevance of these procedures. LEVEL OF EVIDENCE: IV.

Sustained superiority in KOOS subscores after matrix-associated chondrocyte implantation using spheroids compared to microfracture.

PURPOSE: To evaluate the safety and efficacy of matrix-associated autologous chondrocyte implantation (ACI) using spheroids in comparison to arthroscopic microfracture for the treatment of symptomatic cartilage defects of the knee. METHODS: In a prospective multicenter-controlled trial, patients aged between 18 and 50 years, with single symptomatic focal cartilage defects between 1 and 4 cm2 (mean 2.6 ± 0.8, median 2.75, range 1.44-5.00) in the knee were randomized to treatment with ACI with spheroids (n = 52) or microfracture (n = 50). Primary clinical outcome was assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS). Analyses were performed in a defined hierarchical manner where outcomes of ACI were first compared to baseline values followed by a comparison to the microfracture group with repeated-measures ANCOVA with a non-inferiority approach. Subgroup analyses were performed to investigate the influence of age and defect size on the overall KOOS. Secondary clinical outcomes were the magnetic resonance observation of cartilage repair tissue (MOCART), modified Lysholm score and International Knee Documentation Committee (IKDC) examination form. Safety data focused on adverse events. Here the 5 years results are presented at which there were 33 observed cases in the ACI group and 30 in the microfracture group. RESULTS: The overall KOOS and its five subscores were significantly improved compared to baseline for both the ACI and microfracture group. Non-inferiority of ACI to microfracture was confirmed for the overall KOOS and the subscores, while for the subscores activities of daily living, quality of life and sports and recreation of the threshold for superiority was passed. In the ACI group, a notably more rapid initial improvement of the KOOS was found at three months for the older age group compared to the younger age group and the microfracture group. No other differences were found based on age or defect size. In addition, clinical improvement was found for the MOCART, modified Lysholm and IKDC examination form both the ACI and microfracture group. No safety concern related to either treatment was observed. CONCLUSION: This study confirms the safety and efficacy of matrix-associated ACI with spheroids at a mid to long-term follow-up. Non-inferiority of ACI to microfracture was confirmed for the overall KOOS and all subscores, while superiority was reached for the subscores activities of daily living, quality of life and sports and recreation in the ACI group. This underlines the importance of ACI for the young and active patients. LEVEL OF EVIDENCE: I.

Chondrocyte Isolation from Loose Bodies-An Option for Reducing Donor Site Morbidity for Autologous Chondrocyte Implantation.

Loose bodies (LBs) from patients with osteochondritis dissecans (OCD) are usually removed and discarded during surgical treatment of the defect. In this study, we address the question of whether these LBs contain sufficient viable and functional chondrocytes that could serve as a source for autologous chondrocyte implantation (ACI) and how the required prolonged in vitro expansion affects their phenotype. Chondrocytes were isolated from LBs of 18 patients and compared with control chondrocyte from non-weight-bearing joint regions (n = 7) and bone marrow mesenchymal stromal cells (BMSCs, n = 6) obtained during primary arthroplasty. No significant differences in the initial cell yield per isolation and the expression of the chondrocyte progenitor cell markers CD44 + /CD146+ were found between chondrocyte populations from LBs (LB-CH) and control patients (Ctrl-CH). During long-term expansion, LB-CH exhibited comparable viability and proliferation rates to control cells and no ultimate cell cycle arrest was observed within 12 passages respectively 15.3 ± 1.1 mean cumulative populations doublings (CPD). The chondrogenic differentiation potential was comparable between LB-CH and Ctrl-CH, but both groups showed a significantly higher ability to form a hyaline cartilage matrix in vitro than BMSC. Our data suggest that LBs are a promising cell source for obtaining qualitatively and quantitatively suitable chondrocytes for therapeutic applications, thereby circumventing donor site morbidity as a consequence of the biopsies required for the current ACI procedure.

Post-Implantation Inflammatory Responses to Xenogeneic Tissue-Engineered Cartilage Implanted in Rabbit Trachea: The Role of Cultured Chondrocytes in the Modification of Inflammation.

Immune responses to tissue-engineered grafts made of xenogeneic materials remain poorly studied. The scope of current investigations is limited by the lack of information on orthotopically implanted grafts. A deeper understanding of these processes is of great importance since innovative surgical approaches include the implantation of xenogeneic decellularized scaffolds seeded by cells. The purpose of our work is to study the immunological features of tracheal repair during the implantation of tissue-engineered constructs based on human xenogeneic scaffolds modified via laser radiation in rabbits. The samples were stained with hematoxylin and Safranin O, and they were immunostained with antibodies against tryptase, collagen II, vimentin, and CD34. Immunological and inflammatory responses were studied by counting immune cells and evaluating blood vessels and collagen. Leukocyte-based inflammation prevailed during the implantation of decellularized unseeded scaffolds; meanwhile, plasma cells were significantly more abundant in tissue-engineered constructs. Mast cells were insignificantly more abundant in tissue-engineered construct samples. Conclusions: The seeding of decellularized xenogeneic cartilage with chondrocytes resulted in a change in immunological reactions upon implantation, and it was associated with plasma cell infiltration. Tissue-engineered grafts widely differed in design, including the type of used cells. The question of immunological response depending on the tissue-engineered graft composition requires further investigation.

Low postoperative complication rate with high survival rate and good clinical outcome 9 years after autologous chondrocyte transplantation of the knee joint.

PURPOSE: To investigate postoperative complications and associated risk factors for failure following autologous chondrocyte transplantation ("ACT") as well as its long-term survival and clinical function. It was hypothesized that ACT is a safe technique for cartilage repair with a low incidence of postoperative complications and rare rates of revision surgery combined with a high long-term survival and good to excellent clinical outcome in long-term-follow-up. METHODS: All patients undergoing ACT-Cs of the knee joint between 2006 and 2012 at the author's institution were included in this retrospective study. Concomitant procedures had been performed if necessary. Early postoperative complications, revision surgeries, failure and risk factors for those events were evaluated 6 months after the surgery. Long-term clinical outcome was assessed using the Lysholm Score, the Tegner Score, a 10-grade scale for satisfaction and the Visual Analogue Scale (VAS) at a minimum follow-up of 9 years postoperatively. Long-term survival was calculated using revision surgeries, clinical failures and conversion procedures to create a Kaplan-Meier analysis. A subgroup analysis for different defect locations was performed. 139 patients were included in this study (27% female/ 73%male; age 26.7 [21.7; 35.2] years). The median defect size was 4.0 [3.0; 6.0] cm2 (40% medial femoral condyle (MFC), 17% lateral femoral condyle (LFC), 36% patella, 19% trochlea). 97 (70%) of the patients had undergone previous surgery and 84 (60%) underwent concomitant procedures. RESULTS: Postoperatively, 8% of patients had complications (4% bleeding, 2% arthrofibrosis, 2% infection), 7% of patients needed revision surgery. 12% of patients had a prolonged deficit in ROM, that did not require revision surgery. No significant difference in terms of complications was found between the patellofemoral and femorotibial group. Patients demonstrated good patient reported long-term outcomes 9-15 years after the index surgery (Tegner: 4.7 ± 1.8; VAS: 2.4 ± 2.1; Lysholm: 80 ± 14; satisfaction with operation: 7.3 ± 1.9). Survival rates were 88% at 9 years, 85% at 11 years, and 85% at 13 years after the index procedure. Reasons for failure included debridement of ACT (n = 4; 5%), revision ACT (n = 3, 3%), conversion to total knee arthroplasty (n = 3, 3%) and conversion to High tibial osteotomy (HTO) (n = 1; 1%)). CONCLUSION: The present study indicates ACT as an effective treatment option for femorotibial- as well as patellofemoral cartilage defects with a high long-term survival and low conversion rate as well as good long-term results regarding knee function and satisfaction. Postoperative complications needing revision surgery are rare. Prolongated deficits of range of motion appear frequently up to six months especially in patellofemoral defects, but can often be successfully addressed by intensified physiotherapy without requiring an arthrolysis. LEVEL OF EVIDENCE: Level III.