Kyoung-Ho Yoon1, Jae-Young Park1, Jin-Yeon Lee2, EunAh Lee3, Jungsun Lee2, Sang-Gyun Kim1,4. 1. Department of Orthopaedics, Kyung-Hee University Hospital, Seoul, Republic of Korea. 2. R&D Institute, Biosolution Co, Ltd, Seoul, Republic of Korea. 3. Impedance Imaging Research Center, Kyung Hee University, Seoul, Republic of Korea. 4. Department of Orthopedic Surgery, Korea University Ansan Hospital, Gyeongki-do, Republic of Korea.
Abstract
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).
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).
Authors: Benjamin J Bielajew; Ryan P Donahue; Elliott K Lamkin; Jerry C Hu; Vincent C Hascall; Kyriacos A Athanasiou Journal: Biomater Res Date: 2022-07-22