3D GelMA ICC Scaffolds Combined with SW033291 for Bone Regeneration by Modulating Macrophage Polarization
Qian Jiang,
Guo Bai,
Xin Liu,
Yuxiao Chen,
Guangzhou Xu,
Chi Yang,
Zhiyuan Zhang
Affiliations
Qian Jiang
Department of Oral Surgery, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, No 639, Zhizaoju Rd, Shanghai 200011, China
Guo Bai
Department of Oral Surgery, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, No 639, Zhizaoju Rd, Shanghai 200011, China
Xin Liu
Department of Dental Materials, Shanghai Biomaterials Research & Testing Center, Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, No 427, Jumen Rd, Shanghai 200011, China
Yuxiao Chen
Department of Dental Materials, Shanghai Biomaterials Research & Testing Center, Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, No 427, Jumen Rd, Shanghai 200011, China
Guangzhou Xu
Department of Oral Surgery, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, No 639, Zhizaoju Rd, Shanghai 200011, China
Chi Yang
Department of Oral Surgery, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, No 639, Zhizaoju Rd, Shanghai 200011, China
Zhiyuan Zhang
Department of Oral Maxillofacial-Head and Neck Oncology, Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center of Stomatology, No 639, Zhizaoju Rd, Shanghai 200011, China
Despite the interaction between bone marrow mesenchymal stem cells (BMSCs) and macrophages has been found to play a critical role in repairing bone defects, it remains a challenge to develop a desirable tissue engineering scaffold for synchronous regulation of osteogenic differentiation and macrophage polarization. Herein, this study proposed a novel strategy to treat bone defects based on three-dimensional Gelatin Methacryloyl Inverted Colloidal Crystal (3D GelMA ICC) scaffold and an active 15-hydroxyprostaglandin dehydrogenase (15-PGDH) inhibitor SW033291. Specifically, the 3D GelMA ICC scaffolds were firstly prepared by colloidal templating method, which displayed good cell attachment and promoted intercellular interaction among macrophage and BMSCs due to its uniform pore interconnectivity. By combined use of SW033291, the release of Prostaglandin E2 (PGE2) from BMSCs on the GelMA ICC scaffold was significantly upregulated and macrophages M2 polarization was markedly increased. In turn, BMSCs proliferation and osteogenic differentiation was further enhanced by paracrine regulation of M2 macrophage, and thus finally caused more in vivo new bone formation by shaping up a pro-regenerative local immune microenvironment surrounding GelMA ICC scaffold. Our findings demonstrate the potential of 3D GelMA ICC scaffolds combined with SW033291 to become an effective tissue engineering strategy for bone regeneration.
