Autologous Chondrocyte Implantation Research Articles

Limited evidence in support of bone marrow aspirate concentrate as an additive to the bone marrow stimulation for osteochondral lesions of the talus: a systematic review and meta‐analysis

AbstractPurposeBone marrow aspirate concentrate can be used as an additive to surgical treatment of osteochondral lesions of the talus. This systematic literature review aims to study the effect of the additional use of bone marrow aspirate concentrate on top of a surgical treatment for osteochondral lesions of the talus on clinical outcomes compared to surgical treatment alone.MethodsAn online literature search was conducted using PubMed (Medline), Embase (Ovid), and the Cochrane library for all studies comparing a surgical intervention with bone marrow aspirate concentrate, with a surgical intervention without bone marrow aspirate concentrate. The methodological quality was rated according to the methodological index for non‐randomised studies checklist. The primary outcome measure were clinical outcomes. Secondary outcome measures consisted of revision rate, complication rate, radiographic outcome measures and histological analyses. Subgroups were created based on type of surgical intervention used in the studies. If multiple articles were included in a subgroup, a linear random‐effects model was used to compare the bone marrow aspirate concentrate‐augmented group with the control group.ResultsOut of 1006 studies found, eight studies with a total of 718 patients were included. The methodological quality, assessed according to the methodological index for non‐randomised studies checklist, was weak. A significantly better functional outcome measures (p < 0.05) was found in the subgroup treated with bone marrow stimulation + bone marrow aspirate concentrate compared to the group treated with bone marrow stimulation alone, based on three non‐blinded studies. No significant differences regarding clinical outcomes were found in the subgroups comparing matrix‐induced autologous chondrocyte implantation with matrix‐induced bone marrow aspirate concentrate, osteochondral autologous transplantation alone with osteochondral autologous transplantation + bone marrow aspirate concentrate and autologous matrix‐induced chondrogenesis plus peripheral blood concentrate vs. matrix‐associated stem cell transplantation bone marrow aspirate concentrate.ConclusionThere is insufficient evidence to support a positive effect on clinical outcomes of bone marrow aspirate concentrate as an additive to surgical treatment of osteochondral lesions of the talus. However, based on the safety reports and initial results, sufficiently powered, patient‐ and researcher‐blinded, prospective randomised controlled trials are justified and recommended. Until then, we advise not to implement a therapy (addition of bone marrow aspirate concentrate) without clinical evidence that justifies the additional costs involved.Level of evidenceLevel III.

Meniscal Allograft Transplantation Concomitant With Cartilage Repair for Symptomatic Lateral Meniscus-Deficient Knees With Over Two Years of Follow-up.

Background and objective The treatment for symptomatic meniscus-deficient knees with cartilage defects remains challenging on account of insufficient meniscal substitutes. One solution for this might involve combining meniscal allograft transplantation (MAT) and cartilage repair. In this study, we aimed to analyze the effectiveness and safety of MAT concomitant with cartilage repair for symptomatic lateral meniscus-deficient knees in a setting with limited availability of meniscal transplants in Japan. Methods Nine patientswho underwent MAT concomitant with osteochondral transplantation (five) and/or autologous chondrocyte implantations (seven) were followed up for at least two years (mean: 51.2 months, range: 24-84 months). Their demographic data and other characteristics were as follows - mean age: 51.7 years, range: 36-67 years; men/women: 4/5; cause: trauma/discoid meniscus: 8/1; cartilage defect size: mean: 6.7 cm2/knee, range: 1.0-11.3. The effectiveness and safety were evaluated clinically by using the Lysholm Knee Scoring Scale(LKSS) and Japanese Orthopaedic Association (JOA) knee score, physical examination, X-rays, and MRI preoperatively and at one, 12, and 24 months after the implantation. Differences between the variables were analyzed using the Friedman test and Scheffe's multiple comparisons. Results The median LKSS and JOA scores significantly improved from 70 points (range: 21-80) and 35 (25-45) preoperatively to 86.5 (65-98) and 87.5 (80-95) at 24 months after surgery, respectively (p<0.001, p=0.0013). The range of motion (ROM), femorotibial angle, and the lateral joint space showed no significant changes. However, lateral meniscal extrusions (LMEs) increased by 3.0 mm (range: 0-6.3 mm) at one month postoperatively and remained unchanged until two years postoperatively. Treatment failure occurred in one case, which was revised by total knee arthroplasty (TKA) at 18 months postoperatively. Additional surgeries were needed in some cases: lateral meniscal tear (three cases), contracture (two cases), and patellar instability (one case). However, neither infection nor allergic reaction was observed in the blood exams. Conclusions Although MAT concomitant with cartilage repair showed good clinical outcomes, half of the cases needed additional surgeries. Based on our findings, this technique should be adopted only in select cases and performed bya handful of highly experienced surgeons.

Increased risk of reoperation and failure to attain clinically relevant improvement following autologous chondrocyte implantation of the knee in female patients and individuals with previous surgeries: a time-to-event analysis based on the German cartilage registry (KnorpelRegister DGOU)

PurposeThis study aimed to analyze the risk of reoperation following autologous chondrocyte implantation (ACI) of the knee utilizing third-generation ACI products in a time-to-event analysis and report on the associated patient-reported outcome measures (PROM) in case of reoperation.MethodsPatients undergoing ACI were included from a longitudinal database. Patient age, sex, body mass index (BMI), number of previous surgeries, lesion localization, lesion size, symptom duration, as well as time and type of reoperation was extracted. A cox proportional-hazards model was applied to investigate the influence of baseline variables on risk of reoperation. Reoperation was defined as any type of subsequent ipsilateral knee surgery, excluding hardware removal. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was utilized to compare PROM between patients with and without reoperation.ResultsA total of 2039 patients were included with 1359 (66.7%) having a minimum follow-up of 24 months. There were overall 243 reoperations (prevalence 17.9%). Minor arthroscopic procedures (n = 96, 39.5%) and revision cartilage repair procedures (n = 78, 32.1%) were the most common reoperations. Nineteen patients (0.9%) reported conversion arthroplasty at 17.7 (10.4) months after ACI. Female sex (HR 1.5, 95% CI [1.2, 2.0], p = 0.002) and the presence of 1–2 previous surgeries (HR 1.5, 95% CI [1.1, 2.0], p = 0.010), or more than 2 previous surgeries (HR 1.9, 95% CI [1.2, 2.9], p = 0.004) were significantly associated with increased risk of reoperation following ACI. Significantly less patients surpassed the minimal clinically important difference (MCID) in the reoperation group at 24 months regarding the KOOS subscores pain (OR 1.6, 95% CI [1.1, 2.2]), quality of life (OR 2.2, 95% CI [1.6, 3.2]), symptoms (OR 2.0 [1.4, 2.9]), and sports (OR 2.0 [1.4, 2.8]).ConclusionFemale patients and individuals with a history of previous surgeries face an elevated risk of requiring reoperation after undergoing ACI, which is associated with failure to attain clinically relevant improvements. A thorough evaluation of the indications for ACI is paramount, particularly when patients have a history of previous surgeries.Level of evidenceLevel III.

Evidence-based machine learning algorithm to predict failure following cartilage procedures in the knee

IntroductionClinical decision-making is highly based on expert opinion. Machine learning is increasingly used to develop patient-specific risk prediction analysis to improve patient selection prior to surgery. ObjectivesTo develop machine learning algorithms to predict failure of surgical procedures that address cartilage defects of the knee and detect variables associated with failure. MethodsAn institutional database was queried for cartilage procedures performed between 2000 and 2018. Failure was defined as revision cartilage surgery or knee arthroplasty. One hundred and one preoperative and intraoperative features were evaluated as potential predictors. Four machine learning algorithms were trained and internally validated. ResultsOne thousand and ninety-one patients with a minimum follow-up of 2 years were included and underwent chondroplasty (n = 560; 51%), osteochondral allograft transplantation (n = 306; 28%), microfracture (n = 150; 14%), autologous chondrocyte implantation (n = 39; 4%), or osteochondral autograft transplantation (n = 36; 3%). The Random Forest algorithm was the best-performing algorithm, with an area under the curve of 0.765 and a Brier score of 0.135. The most important features for predicting failure were symptom duration, age, body mass index, lesion grade, and total lesion area. Local Interpretable Model-agnostic Explanations analysis provided patient-specific comparisons for the risk of failure of an individual patient being assigned various types of cartilage procedures. ConclusionsMachine learning algorithms were accurate in predicting the risk of failure following cartilage procedures of the knee, with the most important features in descending order being symptom duration, age, body mass index, lesion grade, and total lesion area. Machine learning algorithms may be used to compare the risk of failure of specific patient-procedure combinations in the treatment of cartilage defects of the knee.

Cartilage Biopsy for Autologous Cell–Based Repair of the Knee in the Wide-Awake Setting Using Needle Arthroscopy

Chondral and osteochondral lesions of the knee are a commonly occurring pathology that can pose challenges to the treating surgeon. For the appropriate cartilage injury, autologous cell–based articular cartilage repair techniques have shown promising results. However, these treatments traditionally require 2 separate surgical procedures. Recent advances in needle arthroscopy technology have made it possible to conduct the first stage of autologous chondrocyte implantation surgery in the wide-awake office setting, mitigating cost and resource utilization. The purpose of this technical note is to serve as a proof of concept and describe the process of obtaining a cartilage sample in the wide-awake patient using a needle arthroscope.

Treatment of Articular Cartilage Defects: A Descriptive Analysis of Clinical Characteristics and Global Trends Reported from 2001 to 2020.

To evaluate the clinical characteristics and global trends in the surgical treatment of articular cartilage defects. Studies in English published between January 1, 2001 and December 31, 2020 were retrieved from MEDLINE, WOS, INSPEC, SCIELO, KJD, and RSCI on the "Web of Science." Patient data were extracted, including age, sex, defect location and laterality, duration of follow-up and symptoms, and body mass index (BMI). Data were further stratified according to the surgical method, lesion location, procedural type and geographical area, and time period. A comparative analysis was performed. Overall, 443 studies involving 26,854 patients (mean age, 35.25 years; men, 60.5%) were included. The mean lesion size and patient BMI were 3.51 cm2 and 25.61 kg/m2, respectively. Cartilage defects at the knees, talus, and hips affected 20,850 (77.64%), 3,983 (14.83%), and 1,425 (5.31%) patients, respectively. The numbers of patients who underwent autologous chondrocyte implantation, arthroscopic debridement/chondroplasty, osteochondral allograft (OCA), osteochondral autologous transplantation, and microfracture were 7,114 (26.49%), 5,056 (18.83%), 3,942 (14.68%), 3,766 (14.02%), and 2,835 (10.56%), respectively. European patients were the most numerous and youngest. North American patients had the largest defects. The number of patients increased from 305 in 2001 to 3,017 in 2020. In the last 5 years, the frequency of OCAs showed a greatly increasing trend. Clinical characteristics and global trends in the surgical treatment of articular cartilage defects were revealed. The choice of operation should be based on the patient characteristics and defect location, size, and shape, as well as the patient's preference.

Kinesiophobia and Pain Catastrophizing Leads to Decreased Return to Sport Following Autologous Chondrocyte Implantation but Does Not Affect Return to Work.

To evaluate the effect of fear of reinjury on return to sport (RTS), return to work (RTW), and clinical outcomes following autologous chondrocyte implantation (ACI). A retrospective review of patients who underwent ACI with a minimum of 2 years in clinical follow-up was conducted. Patient-reported outcomes collected included the Visual Analog Scale (VAS) and Knee Injury and Osteoarthritis Outcome Score (KOOS). Kinesiophobia and pain catastrophizing was assessed using the Tampa Scale of Kinesiophobia-11 (TSK-11) and Pain Catastrophizing Scale (PCS), respectively. Patients were surveyed on their RTS and RTW status. Fifty-seven patients (50.9% female) were included in our analysis. Twenty-two (38.6%) patients did not RTS. Of the 35 patients (61.4%) who returned, nearly half (48.6%) returned at a lower level of play. TSK-11 (P = 0.003), PCS (P = 0.001), and VAS pain scores (P < 0.001) were significantly greater in patients that did not RTS than in those who returned. All KOOS subscores analyzed were significantly lower (P < 0.001) in patients that did not RTS than in those who returned at the same level or higher. Of the 44 (77.2%) patients previously employed, 97.7% returned to work. Increasing TSK-11 scores were associated with lower odds of returning to sport (P = 0.003). Fear of reinjury decreases the likelihood that patients will return to sport after ACI. Patients that do not return to sport report significantly greater levels of fear of reinjury and pain catastrophizing and lower clinical knee outcomes. Nearly all patients were able to return to work after surgery. IV case series.

Knee Cartilage Lesion Management-Current Trends in Clinical Practice.

Many patients, particularly those aged above 40, experience knee joint pain, which hampers both sports activities and daily living. Treating isolated chondral and osteochondral defects in the knee poses a significant clinical challenge, particularly in younger patients who are not typically recommended partial or total knee arthroplasty as alternatives. Several surgical approaches have been developed to address focal cartilage defects. The treatment strategies are characterized as palliation (e.g., chondroplasty and debridement), repair (e.g., drilling and microfracture), or restoration (e.g., autologous chondrocyte implantation, osteochondral autograft, and osteochondral allograft). This review offers an overview of the commonly employed clinical methods for treating articular cartilage defects, with a specific focus on the clinical trials conducted in the last decade. Our study reveals that, currently, no single technology fully meets the essential requirements for effective cartilage healing while remaining easily applicable during surgical procedures. Nevertheless, numerous methods are available, and the choice of treatment should consider factors such as the location and size of the cartilage lesion, patient preferences, and whether it is chondral or osteochondral in nature. Promising directions for the future include tissue engineering, stem cell therapies, and the development of pre-formed scaffolds from hyaline cartilage, offering hope for improved outcomes.

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.

Assessment of Cartilage Resected from Osteochondral Lesions of the Talus for Intraoperative Reimplantation

Category: Basic Sciences/Biologics; Arthroscopy Introduction/Purpose: Osteochondral lesions of the talus (OLT) are frequently treated with microfracture and may be augmented with decellularized extracellular matrix or particulated juvenile cartilage. The damaged OLT cartilage is often discarded. Infrequently it is used as a source for autologous chondrocyte expansion and implantation in a subsequent procedure. This resected cartilage has demonstrated variable chondrocyte viability. The influence of cartilage type on chondrocyte viability, whether frayed fibrocartilage from in vivo repair or delaminated hyaline cartilage, remains unknown. Also, little has been reported on the use of the OLT cartilage as a source for immediate cartilage autograft. The purpose of this study is to evaluate chondrocyte quantity and viability from the excised cartilage of OLTs at the time of arthroscopic debridement and microfracture. Methods: Patients aged 18 to 65 undergoing arthroscopic debridement and microfracture of talar OLTs were included. IRB approval of the study protocol was obtained. At the time of ankle arthroscopy, the cartilage from the OLT was collected either by GraftNet™ Autologous tissue collector (GraftNet™ Autologous Tissue Collector, Arthrex; Naples, FL) or manual collection and mincing of the specimen with a scalpel. Chondrocytes were isolated by overnight digestion with 2% collagenase in tissue culture medium at 37°C. The isolated cells were stained with Trypan Blue and counted for total cell number and viability (%), using an automated cell counter. Data collection included patient age, size and location of the OLT, intraoperative surgeon assessment of cartilage type (hyaline cartilage, fibrocartilage, or mixed fibro-hyaline cartilage), histologic determination of cartilage type, weight of the specimen, and chondrocyte cell count and viability. Results: Fourteen OLT specimens were collected. The average size was 0.831 (SD ± 1.10) cm2, and average weight 0.19 (SD ± 0.17) grams. Overall, the average number of chondrocytes was 1.12 x106 (SD ± 1.13 x106) cells/mm2 and 3.99 x106 (SD ± 3.28 x106) cells/gram. The average viability was 72.36% (SD ± 12.25%). Using histologic determination of cartilage type, in hyaline specimens (n = 8, 57.14%) we found 1.08 x106 (SD ± 0.85 x106) chondrocytes/cm2, 70.73% (SD ± 11.73 %) viability. In fibrocartilage specimens (n = 2, 14.29%) we found 0.37 x106 (SD ± 0.10 x106) chondrocytes/cm2, 78.08% (SD ± 22.03%) viability. In mixed cartilage specimens (n = 4, 28.57%) we found 1.58 x106 (SD ± 1.80 x106) cells/cm2, 72.78% (SD ± 11.79%) viability. (Table 1) Conclusion: We found OLT chondrocyte viability of 72.36%, with a trend toward greater chondrocyte concentration and similar viability comparing hyaline and fibro cartilage, respectively. Cartilage type was consistent between intraoperative and histologic assessment in all but four specimens. OLT cartilage has the potential to serve as an immediate intraoperative chondrocyte autograft source for enhancement of talus cartilage repair procedures, eliminating the risk of donor site morbidity and additional surgeries as in culture-based methods. Further study with more patients may shed light on the accuracy of intraoperative cartilage classification, and differences in chondrocyte quantity and viability between cartilage types.

Early Postoperative Complications and Associated Variables After Tibial Tubercle Osteotomy: A 15-Year Experience From a Single Academic Institution.

Tibial tubercle osteotomy (TTO) is a well-established surgical treatment option for patients with patellofemoral disorders. To determine the rate of early (≤90 day) postoperative complications after TTO and variables related to postoperative complications. Case series; Level of evidence, 4. Patients who underwent TTO at a single academic institution within a 15-year period (2008-2022) were identified. All patients with a minimum 90-day follow-up were considered for study inclusion. Exclusion criteria were age younger than 14 years and revision surgery. Patient characteristics, surgical history, and concomitant procedures were identified, and risk factor analysis was performed to identify variables associated with early postoperative complications. A total of 344 knees in 313 patients met eligibility criteria and were included in the final analysis. One intraoperative complication (0.3%), a premature closure of the incision before repair of the vastus medialis, was identified. There were 141 postoperative complications (138 surgical, 3 medical) in 118 patients for a complication rate of 34.3%. The most common complications were stiffness requiring a nonstandard-of-care intervention (16.3%), superficial wound infection/wound dehiscence (8.1%), and hemarthrosis/effusion requiring aspiration (5.8%). Patients experiencing postoperative complications were older (mean difference, 3.49 years; 95% CI, 1.26-5.73 years; P = .002), had a higher mean Charlson Comorbidity Index (mean difference, 0.26; 95% CI, 0.08-0.45; P = .006), and were more likely to be current smokers (P = .015) compared with patients with no complications. Inpatient surgery (defined as surgery in a hospital setting with at least 1 overnight stay) was associated with postoperative complications (odds ratio [OR], 2.29; 95% CI, 1.39-3.77; P = .001); this association remained significant generation of a multivariate model (OR, 2.07; 95% CI, 1.19-3.58; P = .010). Previous surgery on the ipsilateral knee (P < .001) and concomitant autologous chondrocyte implantation (P = .046) were also associated with postoperative complications. The study findings indicated a low intraoperative complication rate (0.3%) and a relatively high early postoperative (≤90 day) complication rate (34.3%) after TTO. Variables associated with postoperative complications included greater age, higher Charlson Comorbidity Index, surgery in an inpatient setting, previous surgery on the ipsilateral knee, and concomitant autologous chondrocyte implantation.

Autologous and Allogeneic Cytotherapies for Large Knee (Osteo)Chondral Defects: Manufacturing Process Benchmarking and Parallel Functional Qualification.

Cytotherapies are often necessary for the management of symptomatic large knee (osteo)-chondral defects. While autologous chondrocyte implantation (ACI) has been clinically used for 30 years, allogeneic cells (clinical-grade FE002 primary chondroprogenitors) have been investigated in translational settings (Swiss progenitor cell transplantation program). The aim of this study was to comparatively assess autologous and allogeneic approaches (quality, safety, functional attributes) to cell-based knee chondrotherapies developed for clinical use. Protocol benchmarking from a manufacturing process and control viewpoint enabled us to highlight the respective advantages and risks. Safety data (telomerase and soft agarose colony formation assays, high passage cell senescence) and risk analyses were reported for the allogeneic FE002 cellular active substance in preparation for an autologous to allogeneic clinical protocol transposition. Validation results on autologous bioengineered grafts (autologous chondrocyte-bearing Chondro-Gide scaffolds) confirmed significant chondrogenic induction (COL2 and ACAN upregulation, extracellular matrix synthesis) after 2 weeks of co-culture. Allogeneic grafts (bearing FE002 primary chondroprogenitors) displayed comparable endpoint quality and functionality attributes. Parameters of translational relevance (transport medium, finished product suturability) were validated for the allogeneic protocol. Notably, the process-based benchmarking of both approaches highlighted the key advantages of allogeneic FE002 cell-bearing grafts (reduced cellular variability, enhanced process standardization, rationalized logistical and clinical pathways). Overall, this study built on our robust knowledge and local experience with ACI (long-term safety and efficacy), setting an appropriate standard for further clinical investigations into allogeneic progenitor cell-based orthopedic protocols.

Costal chondrocyte-derived pellet-type scaffold-free autologous chondrocyte implantation provided acceptable mid-term outcomes in osteochondral defects with up to 10-mm depth.

To evaluate clinical, radiographic, and magnetic resonance (MR) results of costal chondrocyte-derived pellet-type scaffold-free autologous chondrocyte implantation (CCP-ACI) in osteochondral defects (ODs) up to 10-mm depth during 5years of follow-up. Ten patients with CCP-ACI performed in ODs with depth up to 10mm were retrospectively analyzed. The minimum follow-up period was 5years. The median age was 36.5 (range 20-55) years. The median size and the depth of the OD lesion were 4.25 cm2 (range 2-6) and 7.0mm (6-9), respectively. Clinically, the International Knee Documentation Committee, Lysholm, and visual analog scale pain scores were evaluated. Radiographically, the hip‒knee‒ankle (HKA) angle and the Kellgren‒Lawrence (K‒L) grade were assessed. On MR imaging, the magnetic resonance observation of cartilage repair tissue (MOCART) 2.0 score and the defect depth were evaluated. All average clinical scores improved significantly by 1, 2, and 5years postoperatively. The average HKA angle and the proportion of K‒L grade did not change significantly within 5years. The median total MOCART scores were 50 (range 45-65), 50 (35-90), 57.5 (40-90), and 65 (50-85) at 6months, 1year, 2years, and 5years postoperatively, respectively (p = 0.001), with significant improvement at 2years compared to that at 6months postoperatively. The signal intensity of the repair tissue and subchondral change significantly improved from 10 (range 10-10) to 12.5 (10-15) (p = 0.036), and from 10 (10-10) to 17.5 (0-20) (p = 0.017), respectively. Significant improvements were seen at 5years postoperatively for the former and at 2years postoperatively for the latter. The average depths on MR imaging were 6.7, 6.7, 6.8, 6.6, and 6.6mm preoperatively and at 6months, 1year, 2years, and 5years postoperatively with no significant changes (n.s). CCP-ACI provided acceptable mid-term outcomes in ODs up to 10-mm in depth without bone grafting despite of no scaffold. The procedure can be one of minimally invasive treatment options for ODs without scaffold-related problems. IV.

Cartilage Defect Treatment Using High-Density Autologous Chondrocyte Implantation (HD-ACI).

Hyaline cartilage's inability to self-repair can lead to osteoarthritis and joint replacement. Various treatments, including cell therapy, have been developed for cartilage damage. Autologous chondrocyte implantation (ACI) is considered the best option for focal chondral lesions. In this article, we aimed to create a narrative review that highlights the evolution and enhancement of our chondrocyte implantation technique: High-Density-ACI (HD-ACI) Membrane-assisted Autologous Chondrocyte Implantation (MACI) improved ACI using a collagen membrane as a carrier. However, low cell density in MACI resulted in softer regenerated tissue. HD-ACI was developed to improve MACI, implanting 5 million chondrocytes per cm2, providing higher cell density. In animal models, HD-ACI formed hyaline-like cartilage, while other treatments led to fibrocartilage. HD-ACI was further evaluated in patients with knee or ankle defects and expanded to treat hip lesions and bilateral defects. HD-ACI offers a potential solution for cartilage defects, improving outcomes in regenerative medicine and cell therapy. HD-ACI, with its higher cell density, shows promise for treating chondral defects and advancing cartilage repair in regenerative medicine and cell therapy.

Gel-Based Autologous Chondrocyte Implantation (GACI) in the Chondral Defects of the Knee: An Observational Study.

Gel-based autologous chondrocyte implantation (GACI) is known to have superior results when compared to conventional autologous chondrocyte implantation (ACI) in terms of delivery of chondrocytes to the articular cartilage surface with reproducible three-dimensional structural restoration. This study aims to evaluate the short-term outcomes of gel-based autologous chondrocyte implantation (GACI) for the treatment of large focal articular cartilage defects of the knee. This was a prospective observational study among 25 patients who underwent GACI. Primary outcome measures included Lysholm Knee Scoring Scale and IKDC score and secondary outcome measures included MRI assessment of cartilage repair using MOCART. Mean age of the population was 39.8 ± 7.5years. The study found a highly significant improvement in both Lysholm knee score (pre-op: 45.1 to post-op: 72.4) and IKDC score (pre-op: 36.7 to post-op: 78.5) (p < 0.001) at the final follow-up of 24months, even with the mean defect size being 4.5 ± 5.8 cm2. Postoperative MRI showed a mean MOCART score improvement from 39.4 to 67.4 at the final follow-up. No major complications were observed. GACI is an effective and safe treatment option for large focal articular cartilage defects around the knee, with significant improvement in functional scores and low revision rates at medium-term follow-up.

Comparison of Knee Articular Cartilage Defect Size Between Measurements Obtained on Preoperative MRI Versus During Arthrotomy.

Treatment decisions for cartilage defects are often based on lesion size. Magnetic resonance imaging (MRI) is widely used to diagnose cartilage defects noninvasively; however, their size estimated from MRI may differ from defect sizes measured during arthrotomy, especially after debridement to healthy cartilage if undergoing autologous chondrocyte implantation. The purpose of this study was to evaluate the reliability of 2 methods to assess knee cartilage defect size on preoperative MRI and determine their accuracy in predicting postdebridement defect sizes recorded during arthrotomy. It was hypothesized that defect size would be predicted more accurately by the total area of abnormal articular cartilage rather than the area of full-thickness cartilage loss as identified on MRI. Cohort study (diagnosis); Level of evidence, 3. This study included 64 patients (mean age, 41.8 ± 9.6 years) who underwent autologous cell therapy. Each patient received a 3-T MRI at 6.1 ± 3.0 weeks before cell implantation. Three raters, a radiologist, a surgeon, and a scientist, measured (1) the full-thickness cartilage defect area and (2) the total predicted abnormal cartilage area, identified by an abnormal signal on MRI. Interrater reliability was assessed using the intraclass correlation coefficient (ICC). Actual pre- and postdebridement defect sizes were obtained from intraoperative surgical notes. Postdebridement surgical measurements were considered the clinical reference standard and were compared with the radiologist's MRI measurements. Eighty-seven defects were assessed, located on the lateral (n = 8) and medial (n = 26) femoral condyle, trochlea (n = 17), and patella (n = 36). The interrater reliability of the cartilage defect measurements on MRI was good to excellent for the full-thickness cartilage defect area (ICC = 0.74) and the total predicted abnormal cartilage area (ICC = 0.78). The median full-thickness cartilage defect area on MRI underestimated the median postdebridement defect area by 78.3%, whereas the total predicted abnormal cartilage area measurement underestimated the postdebridement defect area by 14.3%. Measuring the full-thickness cartilage defect area on MRI underestimated the area to treat, whereas measuring the total abnormal area provided a better estimate of the actual defect size for treatment.

The AMADEUS score is not a sufficient predictor for functional outcome after autologous chondrocyte implantation (ACI) of the knee: data from the German Cartilage Registry (KnorpelRegister DGOU)

IntroductionThe AMADEUS (Area Measurement And DEpth and Underlying Structures) score has advanced to a commonly used tool for MRI-based chondral defect severity grading prior to cartilage knee surgery. It was the intention of this study to assess the AMADEUS for a potential correlation with clinical data by patient-reported outcome measures (PROMs).MethodsA total of 51 patients undergoing ACI (autologous chondrocyte implantation) between 2016 and 2022 were found eligible and retrospectively analyzed. All patients were registered in the German Cartilage Registry prior to surgery and follow-up data were collected using the Knee Osteoarthritis Outcome score (KOOS), the International Knee Documentation Committee (IKDC) Form and the numeric rating scale (NRS). Pre-operative MRI images were scored by three raters using the AMADEUS classification system, and an overall AMADEUS score was calculated which was subsequently correlated with pre- and post-operative PROMs.ResultsMean patient age was 32.67 ± 8.37 years and mean defect size area 343.04 mm2 ± 139.45 mm2. No correlative capacity of the pre- and postoperative IKDC, KOOS or NRS scores was found with the AMADEUS final score or any of its subscores. From the pre- to postoperative visit, a significant improvement of the PROMs (IKDC: 45.53 ± 21.00 vs. 59.83 ± 17.93, p = 0.04; KOOS Pain: 58.00 ± 16.70 vs. 76.06 ± 19.20, p = 0.03; KOOS ADL: 64.17 ± 18.76 vs. 82.11 ± 16.68, p < 0.01; KOOS Sports: 26.11 ± 18.52 vs. 50.56 ± 23.94, p = 0.01; KOOS QOL: 25.50 ± 14.26 ± 45.28 ± 19.03, p = 0.00) was found. Intraclass correlation coefficients showed an overall good interrater agreement for the AMADEUS total score (ICC = 0.75).ConclusionsStudy results suggest no correlative capacity of the AMADEUS with routinely used PROMs in patients undergoing ACI. Therefore, radiographically assessed cartilage defect characteristics poorly translate to pre- and postoperative patient-reported outcome data.

Early Complication Rates Are Equivalent Between Isolated Cartilage Restoration and Concomitant Cartilage Restoration and Osteotomy of the Knee.

Realignment osteotomy performed concomitantly with cartilage restoration typically requires early restricted weightbearing and can add significant morbidity, potentially leading to an increased risk of early perioperative complications. The purpose of this study was to compare the 30-day complication rates after isolated cartilage restoration (ICR) versus concomitant cartilage restoration and osteotomy (CRO) using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. NSQIP registries between 2006 and 2019 were queried using Current Procedural Terminology codes to identify patients undergoing ICR (autologous chondrocyte implantation, osteochondral autograft transfer, or osteochondral allograft transplantation) and CRO (with concomitant high tibial osteotomy, distal femoral osteotomy, and/or tibial tubercle osteotomy). Complications rates between treatment groups were compared using multivariate logistic regression analyses adjusted for sex, age, steroid use, and respiratory status. A total of 773 ICR and 97 CRO surgical procedures were identified. Mean patient ages were 35.9 years for the ICR group and 31.2 years for the CRO group. Operative time was significantly longer in the CRO group (170.8 min) compared with the ICR group (97.8 min). Multivariate analysis demonstrated no significant differences in rates of PE, VTE, and all-cause readmission between the ICR and CRO groups. No events of wound disruption, SSI and reoperation were found in the CRO group, while the ICR group was characterized by low rates of wound disruption, reoperation, and SSI (<1.1%). These findings further support concomitant osteotomy with cartilage restoration when appropriate and aid surgeons in the preoperative counseling of patients undergoing cartilage restoration treatment.

Revision and Conversion to Arthroplasty Are Low Among Adolescents Undergoing Meniscal Allograft Transplantation Using the Bridge-In-Slot Technique at Midterm Follow-Up

To report midterm outcomes after primary medial and lateral meniscal allograft transplantation (MAT) withfresh-frozen allografts implanted with the bridge-in-slot technique in the adolescent patient population. Adolescent patients less than 18 years old at the time of primary MAT from 1999 to 2016 were retrospectively identified. International Knee Documentation Committee (IKDC) subjective form, Lysholm, and Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales scores were collected before surgery and at 1-year, 2-year, and a minimum 5-year follow-up. Thresholds for achieving clinically significant outcomes were calculated, and the proportion of patients achieving minimal clinically important difference (MCID), patient-acceptable symptomatic state (PASS), and substantial clinical benefit (SCB) was determined. Meniscus reoperation (partial, subtotal, or total meniscectomy, repair, or failure) and failure (revision MAT or conversion to arthroplasty) rates were determined. Forty-four (female n= 33; male n= 11) of 62 identified patients met inclusion criteria and were followed for a mean of 9.5 ± 3.8 years (range, 5.0-17.7). Lateral MAT was performed in most patients (n= 35/44 [80%]). Isolated MAT was performed in 27 (61%) patients. Common concomitant procedures included osteochondral allograft transplantation (32%), autologous chondrocyte implantation (18%), and anterior cruciate ligament reconstruction (14%). MCID, PASS, and SCB were achieved by patients at a minimum 5-year follow-up for IKDC (62%; 76%; 31%), Lysholm (62%; 79%; 23%), and KOOS questionnaires (Pain [65%; 81%; 41%], Symptoms [58%; 81%; 47%], Activities of Daily Living [53%; 77%; 35%], Sport [86%; 75%; 50%], and Quality of Life [59%; 81%; 59%]), respectively. Fourteen patients (32%) underwent reoperation at an average of 5.0±4.3 years (range, 0.8-14.0) after MAT. Three (7%) patients met criteria for failure, requiring revision MAT an average of 3.8 ± 1.1 years (range, 2.8-4.9) after transplantation. No patients underwent arthroplasty. Overall survival free from failure at 1, 2, 5, and 10 years was 100%, 100%, 93%, and 93%, respectively. At the time of final follow-up, 80% of patients reported satisfaction with their current physical status. Primary MAT in adolescent patients resulted in significant and durable functional improvements at mid- to long-term follow-up. At an average of 9.5 years after surgery, meniscal reoperation rate was 32% whereas graft survival free of revision MAT was 93%. Adolescents undergoing MAT demonstrated similar functional outcomes and graft survivability when compared to available adult MAT literature. Level IV, retrospective case series.

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.