BACKGROUND Because articular chondrocyte-based autologous chondrocyte implantations (ACIs) have restrictively restored articular cartilage defects, alternative cell sources as a new therapeutic option for cartilage repair have been introduced. PURPOSE To assess whether implantation of a costal chondrocyte-derived pellet-type (CCP) ACI allows safe, functional, and structural restoration of full-thickness cartilage defects in the knee. STUDY DESIGN Case series; Level of evidence, 4. METHODS In this first-in-human study, 7 patients with symptomatic, full-thickness cartilage lesions were enrolled. The chondrocytes isolated from the patients' costal cartilage were expanded, followed by 3-dimensional pellet culture to prepare the CCP-ACI. Implantation of the pellets was performed via minimal arthrotomy and secured with a fibrin sealant. Clinical scores, including the International Knee Documentation Committee (IKDC) subjective, Lysholm, and Tegner activity scores, were estimated preoperatively and at 1, 2, and 5 years postoperatively. High-resolution magnetic resonance imaging was also performed to evaluate cartilage repair as well as to calculate the MOCART (magnetic resonance observation of cartilage repair tissue) score. RESULTS The costal chondrocytes of all patients formed homogeneous-sized pellets, which showed the characteristics of the hyaline cartilaginous tissue with lacunae-occupied chondrocytes surrounded by glycosaminoglycan and type II collagen-rich extracellular matrix. There were no treatment-related serious adverse events during the 5-year follow-up period. Significant improvements were seen in all clinical scores from preoperative baseline to the 5-year follow-up (IKDC subjective score, 34.67 to 75.86; Lysholm score, 34.00 to 85.33; Tegner activity score, 1.17 to 4.67; and MOCART score, 28.33 to 83.33). Two patients had complete defect filling on magnetic resonance imaging evaluation at 1 year. Moreover, at 5 years postoperatively, complete defect filling was observed in 4 patients, and hypertrophy or incomplete defect filling (50%-100%) was observed in 2 patients. CONCLUSION The overall results of this clinical study suggest that CCP-ACI can emerge as a promising therapeutic option for articular cartilage repair with good clinical outcomes and structural regeneration and with stable results at midterm follow-up. REGISTRATION NCT03517046 ( ClinicalTrials.gov identifier).

中文翻译：

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肋软骨衍生球型自体软骨植入治疗关节软骨缺损。

背景技术由于基于关节软骨细胞的自体软骨细胞植入（ACI）具有限制性地修复了关节软骨缺损，因此已经引入了替代细胞来源作为软骨修复的新治疗选择。目的评估是否植入肋软骨细胞源性颗粒型（CCP）ACI可以安全，功能和结构上恢复膝全层软骨缺损。研究设计案例系列；证据级别，第4级。方法该首次人类研究纳入了7例有症状，全层软骨病变的患者。将从患者肋软骨分离的软骨细胞进行扩增，然后进行3维沉淀培养以制备CCP-ACI。通过最小限度的关节切开术进行小球的植入，并用纤维蛋白密封剂固定。临床评分包括术前，术后1、2和5年，包括国际膝关节文献委员会（IKDC）主观评分，Lysholm和Tegner活动评分。还进行了高分辨率磁共振成像，以评估软骨修复以及计算MOCART（软骨修复组织的磁共振观察）评分。结果所有患者的肋软骨细胞均形成均一大小的颗粒，显示出透明软骨组织的特征，其腔内充满了腔隙性软骨细胞，周围被糖胺聚糖和富含II型胶原的细胞外基质包围。在5年的随访期内，没有与治疗相关的严重不良事件。从术前基线到5年随访的所有临床评分均有明显改善（IKDC主观评分从34.67降低到75.86; Lysholm评分从34.00降低到85.33; Tegner活动评分从1.17降低到4.67; MOCART评分从28.33降低到83.33 ）。1名患者在磁共振成像评估中有2名患者完全缺损。而且，在术后5年，有4例患者观察到完全缺损，并且有2例患者观察到肥大或不完全缺损（50％-100％）。结论该临床研究的总体结果表明，CCP-ACI有望成为关节软骨修复的有前途的治疗选择，其临床效果和结构再生良好，中期随访结果稳定。注册号NCT03517046（ClinicalTrials.gov标识符）。34.67至75.86；Lysholm得分：34.00至85.33；特格纳活动评分，从1.17到4.67；和MOCART得分从28.33降至83.33）。1名患者在磁共振成像评估中有2名患者完全缺损。而且，在术后5年，有4例患者观察到完全缺损，并且有2例患者观察到肥大或不完全缺损（50％-100％）。结论该临床研究的总体结果表明，CCP-ACI有望成为关节软骨修复的有前途的治疗选择，其临床效果和结构再生良好，中期随访结果稳定。注册号NCT03517046（ClinicalTrials.gov标识符）。34.67至75.86；Lysholm得分：34.00至85.33；特格纳活动评分，从1.17到4.67；和MOCART得分从28.33降至83.33）。1名患者在磁共振成像评估中有2名患者完全缺损。而且，在术后5年，有4例患者观察到完全缺损，并且有2例患者观察到肥大或不完全缺损（50％-100％）。结论该临床研究的总体结果表明，CCP-ACI有望成为关节软骨修复的有前途的治疗选择，其临床效果和结构再生良好，中期随访结果稳定。注册号NCT03517046（ClinicalTrials.gov标识符）。1名患者在磁共振成像评估中有2名患者完全缺损。而且，在术后5年，有4例患者观察到完全缺损，并且有2例患者观察到肥大或不完全缺损（50％-100％）。结论该临床研究的总体结果表明，CCP-ACI有望成为关节软骨修复的有前途的治疗选择，其临床效果和结构再生良好，中期随访结果稳定。注册号NCT03517046（ClinicalTrials.gov标识符）。1名患者在磁共振成像评估中有2名患者完全缺损。而且，在术后5年，有4例患者观察到完全缺损，并且有2例患者观察到肥大或不完全缺损（50％-100％）。结论该临床研究的总体结果表明，CCP-ACI有望成为关节软骨修复的有前途的治疗选择，其临床效果和结构再生良好，中期随访结果稳定。注册号NCT03517046（ClinicalTrials.gov标识符）。结论该临床研究的总体结果表明，CCP-ACI有望成为关节软骨修复的有前途的治疗选择，其临床效果和结构再生良好，中期随访结果稳定。注册号NCT03517046（ClinicalTrials.gov标识符）。结论：本临床研究的总体结果表明，CCP-ACI有望成为关节软骨修复的有前途的治疗选择，其临床效果和结构再生良好，中期随访结果稳定。注册号NCT03517046（ClinicalTrials.gov标识符）。