Three-Dimensional Cartilage Regeneration Using Engineered Cartilage Gel With a 3D-Printed Polycaprolactone Framework

Gaoyang Wu; Lixing Lu; Zheng Ci; Yahui Wang; Runjie Shi; Guangdong Zhou; Shengli Li

doi:10.3389/fbioe.2022.871508

Three-Dimensional Cartilage Regeneration Using Engineered Cartilage Gel With a 3D-Printed Polycaprolactone Framework

Front Bioeng Biotechnol. 2022 May 24:10:871508. doi: 10.3389/fbioe.2022.871508. eCollection 2022.

Authors

Gaoyang Wu¹, Lixing Lu², Zheng Ci^{3

4}, Yahui Wang⁴, Runjie Shi^{2

5}, Guangdong Zhou^{1

3

4}, Shengli Li¹

Affiliations

¹ Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ National Tissue Engineering Center of China, Shanghai, China.
⁴ Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Ear Institute Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵ Research Institute of Plastic Surgery, Weifang Medical University, Weifang, China.

Abstract

The feasibility of the three-dimensional (3D) cartilage regeneration technology based on the "steel (framework)-reinforced concrete (engineered cartilage gel, ECG)" concept has been verified in large animals using a decalcified bone matrix (DBM) as the framework. However, the instability of the source, large sample variation, and lack of control over the 3D shape of DBM have greatly hindered clinical translation of this technology. To optimize cartilage regeneration using the ECG-framework model, the current study explores the feasibility of replacing the DBM framework with a 3D-printed polycaprolactone (PCL) framework. The PCL framework showed good biocompatibility with ECG and achieved a high ECG loading efficiency, similar to that of the DBM framework. Furthermore, PCL-ECG constructs caused a milder inflammatory response in vivo than that induced by DBM-ECG constructs, which was further supported by an in vitro macrophage activation experiment. Notably, the PCL-ECG constructs successfully regenerated mature cartilage and essentially maintained their original shape throughout 8 weeks of subcutaneous implantation. Quantitative analysis revealed that the GAG and total collagen contents of the regenerated cartilage in the PCL-ECG group were significantly higher than those in the DBM-ECG group. The results indicated that the 3D-printed PCL framework-a clinically approved biomaterial with multiple advantages including customizable shape design, mechanical strength control, and standardized production-can serve as an excellent framework for supporting the 3D cartilage regeneration of ECG. This provides a feasible novel strategy for the clinical translation of ECG-based 3D cartilage regeneration.

Keywords: 3D cartilage regeneration; Polycaprolactone; engineered cartilage gel; inflammatory response; tissue engineering.