An Injectable Platform of Engineered Cartilage Gel and Gelatin Methacrylate to Promote Cartilage Regeneration

Wei Xu; Tao Wang; Yahui Wang; Xiaodi Wu; Yujie Chen; Daiying Song; Zheng Ci; Yilin Cao; Yujie Hua; Guangdong Zhou; Yu Liu

doi:10.3389/fbioe.2022.884036

An Injectable Platform of Engineered Cartilage Gel and Gelatin Methacrylate to Promote Cartilage Regeneration

Front Bioeng Biotechnol. 2022 Apr 14:10:884036. doi: 10.3389/fbioe.2022.884036. eCollection 2022.

Authors

Wei Xu^{1

2

3}, Tao Wang^{1

2

3}, Yahui Wang², Xiaodi Wu^{1

2

3}, Yujie Chen⁴, Daiying Song^{1

2

3}, Zheng Ci⁵, Yilin Cao^{2

3}, Yujie Hua^{2

3}, Guangdong Zhou^{1

2

3}, Yu Liu^{1

2

3

5}

Affiliations

¹ Research Institute of Plastic Surgery, Wei Fang Medical College, Weifang, China.
² National Tissue Engineering Center of China, Shanghai, China.
³ Shanghai Key Laboratory of Tissue Engineering, Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Stem Cell Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, China.
⁵ Shanghai Resthetic Bio CO., LTD, Shanghai, China.

Abstract

Cell-hydrogel constructs are frequently used as injectable platforms for irregular cartilage regeneration. However, cell-hydrogel constructs have obvious disadvantages, such as long culture times, high probability of infection, and poor cartilage formation capacity, significantly limiting their clinical translation. In this study, we aimed to develop a novel injectable platform comprising engineered cartilage gel (ECG) and gelatin methacrylate (GelMA) to improve cartilage regeneration. We first prepared an ECG by cutting the in vitro engineered cartilage sheet into pieces. The chondrocytes and ECG were evenly encapsulated into GelMA to form Cell-GelMA and ECG-GelMA constructs. The ECG-GelMA construct exhibited preferred gel characteristics and superior biocompatibility compared with the Cell-GelMA construct counterpart. After subcutaneous implantation in nude mice and goat, both gross views and histological evaluations showed that the ECG-GelMA construct achieved more homogenous, stable, and mature cartilage regeneration than the Cell-GelMA construct. Immunological evaluations showed that ECG-GelMA had a mitigatory immunologic reaction than the Cell-GelMA construct. Overall, the results suggest that the ECG-GelMA is a promising injectable platform for cartilage regeneration that may advance clinical translation.

Keywords: cartilage regeneration; cell-hydrogel; engineered cartilage gel; immune response; injectable platform.