A low-temperature-printed hierarchical porous sponge-like scaffold that promotes cell-material interaction and modulates paracrine activity of MSCs for vascularized bone regeneration

Meifei Lian; Binbin Sun; Yu Han; Bin Yu; Weiwei Xin; Ruida Xu; Bing Ni; Wenbo Jiang; Yongqiang Hao; Xiuyin Zhang; Yi Shen; Zhiguang Qiao; Kerong Dai

doi:10.1016/j.biomaterials.2021.120841

A low-temperature-printed hierarchical porous sponge-like scaffold that promotes cell-material interaction and modulates paracrine activity of MSCs for vascularized bone regeneration

Biomaterials. 2021 Jul:274:120841. doi: 10.1016/j.biomaterials.2021.120841. Epub 2021 Apr 30.

Authors

Meifei Lian¹, Binbin Sun², Yu Han², Bin Yu³, Weiwei Xin⁴, Ruida Xu⁴, Bing Ni⁵, Wenbo Jiang², Yongqiang Hao², Xiuyin Zhang⁶, Yi Shen⁷, Zhiguang Qiao⁸, Kerong Dai⁹

Affiliations

¹ Clinical and Translational Research Center for 3D Printing Technology, Medical 3D Printing Innovation Research Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200125, China; Department of Prosthodontics, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
² Clinical and Translational Research Center for 3D Printing Technology, Medical 3D Printing Innovation Research Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200125, China; Department of Orthopaedic Surgery, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
³ Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
⁴ Department of Orthopaedic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201112, China.
⁵ School of Life Science, East China Normal University, Shanghai, 200241, China.
⁶ Department of Prosthodontics, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
⁷ Department of Orthopaedic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201112, China. Electronic address: mrshenyi@126.com.
⁸ Clinical and Translational Research Center for 3D Printing Technology, Medical 3D Printing Innovation Research Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200125, China; Department of Orthopaedic Surgery, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Department of Orthopaedic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201112, China. Electronic address: lambert_jo@126.com.
⁹ Clinical and Translational Research Center for 3D Printing Technology, Medical 3D Printing Innovation Research Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200125, China; Department of Orthopaedic Surgery, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. Electronic address: krdai@163.com.

PMID: 33984633
DOI: 10.1016/j.biomaterials.2021.120841

Abstract

Mesenchymal stem cells (MSCs) secrete paracrine trophic factors that are beneficial for tissue regeneration. In this study, a sponge-like scaffold with hierarchical and interconnected pores was developed using low-temperature deposition modeling (LDM) printing. Its effects on the cellular behavior, especially on the paracrine secretion patterns of MSCs, were comprehensively investigated. We found that compared with the scaffolds printed via the fused deposition modeling (FDM) technique, the LDM-printed sponges enhanced the adhesion, retention, survival, and ingrowth of MSCs and promoted cell-material interactions. Moreover, the paracrine functions of the cultured MSCs on the LDM-printed sponges were improved, with significant secretion of upregulated immunomodulatory, angiogenic, and osteogenic factors. MSCs on the LDM-printed sponges exert beneficial paracrine effects on multiple regenerative processes, including macrophage polarization, tube formation, and osteogenesis, verifying the enhanced immunomodulatory, angiogenic, and osteogenic potential. Further protein function assays indicated that focal adhesion kinase (FAK), downstream AKT, and yes-associated-protein (YAP) signaling might participate in the required mechanotransductive pathways, through which the hierarchical porous structures stimulated the paracrine effects of MSCs. In a rat distal femoral defect model, the MSC-laden LDM-printed sponges significantly promoted vascularized bone regeneration. The results of the present study demonstrate that the hierarchical porous biomimetic sponges prepared via LDM printing have potential applications in tissue engineering based on their cell-material interaction promotion and MSC paracrine function modulation effects. Furthermore, our findings suggest that the optimization of biomaterial properties to direct the paracrine signaling of MSCs would enhance tissue regeneration.

Keywords: Angiogenesis; Hierarchical pores; Immunomodulation; Mesenchymal stem cells; Paracrine function; Vascularized bone regeneration.

Publication types

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

MeSH terms

Animals
Bone Regeneration
Cell Differentiation
Mesenchymal Stem Cells*
Osteogenesis
Porosity
Rats
Temperature
Tissue Engineering
Tissue Scaffolds