Research Article: Optimization of TGF-β1-transduced chondrocytes for cartilage regeneration in a 3D printed knee joint model

Date Published: May 23, 2019

Publisher: Public Library of Science

Author(s): Jiyong Ahn, Seon Ae Kim, Ki Won Kim, Joon Hyuck Oh, Seok Jung Kim, Dong-Gyu Jo.

http://doi.org/10.1371/journal.pone.0217601

Abstract

A cell therapy product of transforming growth factor (TGF)-β1-transduced chondrocytes has been commercialized to treat osteoarthritis of the knee via intra-articular injection. The need for arthroscopic application of the cells to simultaneously treat intra-articular pathologies of knee osteoarthritis is increasingly urgent. The purpose of this study was to optimize TGF-β1-transduced chondrocytes for arthroscopic application. The optimal composition of chondrocytes and thrombin was initially determined by measuring the consolidation time of a diverse ratio of chondrocytes and thrombin mixed with 1 ml of fibrinogen. The consolidation time of the diverse ratio of fibrinogen and atelocollagen mixed with the determined optimal ratio of chondrocytes and thrombin was evaluated. The mixture of the determined optimal ratio of TGF-β1-transduced chondrocytes, atelocollagen, fibrinogen, and thrombin was applied to the cartilage defect of the 3D printed knee joint model arthroscopically. The status of the mixture in the defect was then evaluated. Chondrogenic activities of TGF-β1-transduced chondrocytes mixed with atelocollagen were evaluated. The determined ratio of TGF-β1-transduced chondrocytes to thrombin was 8:2 and that of fibrin to atelocollagen was also 8:2. Excellent maintenance of conformation of the mixture of TGF-β1-transduced chondrocytes, atelocollagen, fibrinogen, and thrombin in the cartilage defect of the 3D printed knee joint model was observed arthroscopically. Increased chondrogenic activities were observed in the group of TGF-β1-transduced chondrocytes mixed with atelocollagen. TGF-β1-transduced chondrocytes can be applied arthroscopically to treat cartilage defects of the knee at an optimized mixing ratio of atelocollagen, fibrinogen, and thrombin.

Partial Text

Articular cartilage is a hyaline cartilage that does not possess blood vessels, nerves, or lymphatics.[1] Damage or degeneration of articular cartilage can contribute to the development and progression of osteoarthritis.[2] Treatments for damaged articular cartilage includes microfracture, osteochondral autograft transplantation, and autologous chondrocyte implantation. Among these treatment options, autologous chondrocyte implantation has been considered the most effective.[3–6] However, such treatments focus on focal cartilage defects and are not effective for arthritis treatment.[7,8] Moreover, autologous chondrocyte implantation requires two successive operations, including tissue biopsy and implantation after cell culture.[9] Therefore, autologous chondrocyte implantation is a burdensome treatment for both doctors and patients due to its numerous potential problems.[10]

This study was performed to demonstrate the advantages of TGF-β1-transduced chondrocytes, atelocollagen, fibrin, and thrombin injections for maximizing the efficacy of the cartilage regeneration procedure. The optimized ratio of TGF-β1-transduced chondrocytes, atelocollagen, fibrin, and thrombin was determined by carrying out several theoretically possible combination experiments using the materials used for arthroscopic surgery.

Our study provides an appropriate mixing ratio of TGF-β1-transduced chondrocytes, atelocollagen, fibrin, and thrombin. The results also present preliminary data on the surgical application of TGF-β1-transduced chondrocytes based on clinical simulation using 3D-printed joint models. TGF-β1-transduced chondrocytes can be applied arthroscopically to treat cartilage defects of the knee at an optimized mixing ratio of atelocollagen, fibrinogen, and thrombin.

 

Source:

http://doi.org/10.1371/journal.pone.0217601