3D-Printed Scaffolds Promote Angiogenesis by Recruiting Antigen-Specific T Cells
Cuidi Li,
Zhenjiang Ma,
Wentao Li,
Tianyang Jie,
Liping Zhong,
Hongfang Chen,
Wenhao Wang,
Jinwu Wang,
Wenguo Cui,
Yongxiang Zhao
Affiliations
Cuidi Li
Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Zhenjiang Ma
Department of Orthopedic Surgery, Shanghai Key Laboratory of Orthopedic Implants, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
Wentao Li
Department of Orthopedic Surgery, Shanghai Key Laboratory of Orthopedic Implants, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
Tianyang Jie
Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Liping Zhong
National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Theranostics, Guangxi Medical University, Nanning 530021, China
Hongfang Chen
Department of Orthopedic Surgery, Shanghai Key Laboratory of Orthopedic Implants, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
Wenhao Wang
Department of Orthopedic Surgery, Shanghai Key Laboratory of Orthopedic Implants, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
Jinwu Wang
Department of Orthopedic Surgery, Shanghai Key Laboratory of Orthopedic Implants, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; Corresponding authors.
Wenguo Cui
Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Corresponding authors.
Yongxiang Zhao
National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Theranostics, Guangxi Medical University, Nanning 530021, China; Corresponding authors.
The immune response after implantation is a primary determinant of the tissue-repair effects of three-dimensional (3D)-printed scaffolds. Thus, scaffolds that can subtly regulate immune responses may display extraordinary functions. Inspired by the angiogenesis promotion effect of humoral immune response, we covalently combined mesoporous silica microrod (MSR)/polyethyleneimine (PEI)/ovalbumin (OVA) self-assembled vaccines with 3D-printed calcium phosphate cement (CPC) scaffolds for local antigen-specific immune response activation. With the response activated, antigen-specific CD4+ T helper 2 (Th2) cells can be recruited to promote early angiogenesis. The silicon (Si) ions from MSRs can accelerate osteogenesis, with an adequate blood supply being provided. At room temperature, scaffolds with uniformly interconnected macropores were printed using a self-setting CPC-based printing paste, which promoted the uniform dispersion and structural preservation of functional polysaccharides oxidized hyaluronic acid (OHA) inside. Sustained release of OVA was achieved with MSR/PEI covalently attached to scaffolds rich in aldehyde groups as the vaccine carrier. The vaccine-loaded scaffolds effectively recruited and activated dendritic cells (DCs) for antigen presentation and promoted the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. When embedded subcutaneously in vivo, the vaccine-loaded scaffolds increased the proportion of Th2 cells in the spleen and locally recruited antigen-specific T cells to promote angiogenesis in and around the scaffold. Furthermore, the result in a rat skull defect-repair model indicated that the antigen-specific vaccine-loaded scaffolds promoted the regeneration of vascularized bone. This method may provide a novel concept for patient-specific implant design for angiogenesis promotion.
