A 3D-printed PRP-GelMA hydrogel promotes osteochondral regeneration through M2 macrophage polarization in a rabbit model

Guangyao Jiang; Sihao Li; Kang Yu; Bin He; Jianqiao Hong; Tengjing Xu; Jiahong Meng; Chenyi Ye; Yazhou Chen; Zhongli Shi; Gang Feng; Weishan Chen; Shigui Yan; Yong He; Ruijian Yan

doi:10.1016/j.actbio.2021.04.010

A 3D-printed PRP-GelMA hydrogel promotes osteochondral regeneration through M2 macrophage polarization in a rabbit model

Acta Biomater. 2021 Jul 1:128:150-162. doi: 10.1016/j.actbio.2021.04.010. Epub 2021 Apr 22.

Authors

Guangyao Jiang¹, Sihao Li¹, Kang Yu², Bin He¹, Jianqiao Hong¹, Tengjing Xu¹, Jiahong Meng¹, Chenyi Ye¹, Yazhou Chen¹, Zhongli Shi¹, Gang Feng¹, Weishan Chen¹, Shigui Yan³, Yong He⁴, Ruijian Yan⁵

Affiliations

¹ Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jie Fang Road, Hangzhou 310009, China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejinag Province, Hangzhou 310009, China.
² State Key Laboratory of Fluid Power and Mechatronic Systems, College of Mechanical Engineering, Zhejiang University, Hangzhou 310027, China.
³ Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jie Fang Road, Hangzhou 310009, China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejinag Province, Hangzhou 310009, China. Electronic address: zrjwsj@zju.edu.cn.
⁴ State Key Laboratory of Fluid Power and Mechatronic Systems, College of Mechanical Engineering, Zhejiang University, Hangzhou 310027, China. Electronic address: yonghe@zju.edu.cn.
⁵ Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jie Fang Road, Hangzhou 310009, China. Electronic address: yanruijian@zju.edu.cn.

PMID: 33894346
DOI: 10.1016/j.actbio.2021.04.010

Abstract

Osteochondral regeneration is an orchestrated process of inflammatory immunity, host cell response, and implant degradation in tissue engineering. Here, the effects of a platelet-rich plasma (PRP)-gelatin methacryloyl (GelMA) hydrogel scaffold fabricated using the digital micro-mirror device (DMD) technique for osteochondral repair were investigated in a rabbit model. GelMA hydrogels with different PRP concentrations were fabricated, and their roles in bone marrow mesenchymal stem cells (BMSCs) and macrophage polarization in vitro were investigated. The incorporation of 20% PRP into the hydrogel showed optimal effects on the proliferation, migration, and osteogenic and chondrogenic differentiation of BMSCs. The 20% PRP-GelMA (v/v) hydrogel also promoted M2 polarization with high expression of Arg1 and CD206. Compared to the 20% PRP group, the 50% PRP group showed similar biological roles in BMSCs but less extent of osteogenesis. In the vivo study, the 20% PRP-GelMA composite was used for osteochondral reconstruction and showed more cartilage and subchondral bone regeneration than that observed using the pure GelMA hydrogel. The PRP-GelMA group exhibited more M2 macrophage infiltration and less M1 macrophage presentation at three time points as compared to the nontreatment group. The expression of Arg1 in the PRP-GelMA group increased significantly at 6 weeks but decreased to a lower level at 12 weeks, while CD163 showed sustained high expression until 18 weeks. Our findings demonstrated that the 3D-printed PRP-GelMA composite could promote osteochondral repair through immune regulation by M2 polarization and could be a potential candidate for osteochondral tissue engineering. STATEMENT OF SIGNIFICANCE: PRP-GelMA hydrogels promoted the migration and osteogenic and chondrogenic differentiation of BMSCs. PRP-GelMA hydrogels participated in immune regulation and M1-to-M2 transition of macrophages. PRP-GelMA hydrogels coordinated and promoted several overlapping osteochondral repair events, including dynamic immune regulation, chemotaxis of MSCs, and osteochondral differentiation. PRP-GelMA hydrogels showed superior cartilage and subchondral bone repair properties.

Keywords: Gelatin methacrylate; Hydrogel; Macrophage; Osteochondral defect; Platelet-rich plasma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Gelatin* / pharmacology
Hydrogels / pharmacology
Macrophages
Platelet-Rich Plasma*
Printing, Three-Dimensional
Rabbits
Tissue Engineering
Tissue Scaffolds

Substances

Hydrogels
Gelatin