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《工程(英文)》 >> 2022年 第17卷 第10期 doi: 10.1016/j.eng.2021.05.018

募集抗原特异性T细胞的3D打印支架促进血管化

a 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
b 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
c 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

# These authors contributed equally to this work.

收稿日期: 2021-04-01 修回日期: 2021-05-25 录用日期: 2021-05-30 发布日期: 2021-08-17

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摘要

3D打印支架植入后激起的免疫反应是组织修复效果的主要决定性因素。因此,巧妙调控免疫反应的支架材料具有高效修复组织的潜能。本研究受抗原特异性免疫反应对血管新生促进作用的启发,通过动态共价键将介孔二氧化硅微棒(MSR)/聚乙烯亚胺(PEI)/卵清蛋白(OVA)自组装疫苗与3D打印自固化磷酸钙骨水泥(CPC)基支架结合,构建了一种具有调控局部体液免疫反应功能的组织修复支架。通过局部释放OVA激活体液免疫反应,支架可有效募集抗原特异性CD4+ 2 型辅助性T细胞(Th2 细胞),从而促进支架植入早期的血管新生;在提供充足和丰富的血供环境的同时,MSR微棒中释放的硅离子还能有效加速骨再生。在室温下稳定成型的自固化磷酸钙基打印浆料能够促进功能性氧化透明质酸在材料中的均匀分布和结构保持,并构建具有均匀连通孔道的支架。将MSR/PEI 作为抗原载体共价结合于富含醛基的支架,可实现OVA的稳定释放。在体外实验中,该疫苗负载支架有效募集并激活了树突细胞使树突细胞呈递抗原,还促进了骨髓间充质干细胞(BMSC)成骨分化。在皮下包埋实验中,疫苗负载支架增加了Th2 细胞在脾脏中的比例,局部募集了抗原特异性T细胞并促进了支架内的血管新生。此外,原位颅骨缺损修复模型结果表明,负载疫苗的支架可促进血管化骨组织再生。总之,该方法为具有促进血管新生功能个性化植入体的设计提供了一种新思路。

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