Safety and Efficacy of Kartigen® in Treating Cartilage Defects: A Randomized, Controlled, Phase I Trial.

Yen-Liang Liu,Ming-Chia Yang,Hwa-Chang Liu,Tiffany Ting-Fang Shih,Chih-Hung Chang,Jyh-Horng Wang,Tzu-Shang Thomas Liu,Feng-Huei Lin,Chun-Che Yen

doi:10.3390/polym13183029

Abstract

Here, we aimed to investigate the safety and preliminary efficacy of Kartigen®, a matrix with autologous bone marrow mesenchymal stem cell-derived chondrocyte precursors embedded in atelocollagen. As a surgical graft, Kartigen® was implanted onto the cartilage defects at the weight-bearing site of the medial femoral condyle of the knee. Fifteen patients were enrolled and stratified into two groups, undergoing either Kartigen® implantation (n = 10) or microfracture (control group, n = 5). The primary endpoint was to evaluate the safety of Kartigen® by monitoring the occurrence of adverse events through physician queries, physical examinations, laboratory tests, and radiological analyses for 2 years. There were no infections, inflammations, adhesions, loose body, or tumor formations in the Kartigen®-implanted knees. The preliminary efficacy was assessed using the International Knee Documentation Committee (IKDC) score, visual analog scale, and second-look arthroscopy. The postoperative IKDC scores of the Kartigen® group significantly improved in the 16th week (IKDC = 62.1 ± 12.8, p = 0.025), kept increasing in the first year (IKDC = 78.2 ± 15.4, p < 0.005), and remained satisfactory in the second year (IKDC = 73.6 ± 13.8, p < 0.005), compared to the preoperative condition (IKDC = 47.1 ± 17.0), while the postoperative IKDC scores of the control group also achieved significant improvement in the 28th week (IKDC = 68.5 ± 6.1, p = 0.032) versus preoperative state (IKDC = 54.0 ± 9.1). However, the IKDC scores decreased in the first year (IKDC = 63.5 ± 11.6) as well as in the second year (IKDC = 52.6 ± 16.4). Thirteen patients underwent second-look arthroscopy and biopsy one year after the operation. The Kartigen® group exhibited integration between Kartigen® and host tissue with a smooth appearance at the recipient site, whereas the microfracture group showed fibrillated surfaces. The histological and immunohistochemical analyses of biopsy specimens demonstrated the columnar structure of articular cartilage and existence of collagen type II and glycosaminoglycan mimic hyaline cartilage. This study indicates that Kartigen® is safe and effective in treating cartilage defects.

Highlights

Cartilage defects are highly prevalent joint disorders and leading causes of disability and chronic pain in the world [1]
This study was an open-label, controlled, randomized, single-center, phase I clinical trial to evaluate the clinical safety of Kartigen® and its clinical improvements versus microfracture
The development of Kartigen® was started from our previous study using atelocollagenembedded chondrogenic bone marrow mesenchymal stem cells (BMSCs) to repair the full thickness of cartilage defect in miniature pigs [51]

Summary

Introduction

Cartilage defects are highly prevalent joint disorders and leading causes of disability and chronic pain in the world [1]. Multiple surgical treatments have been developed to promote cartilage healing, such as abrasion arthroplasty [7], microfracture [8,9], and mosaicplasty [10,11]. These surgical approaches are usually associated with fibrocartilage formation [12,13], limited tissue sources [14], and donor-site morbidity [15], and its long-term efficacy remains controversial [16]

Objectives

Methods

Conclusion