Localized delivery of FTY-720 from 3D printed cell-laden gelatin/silk fibroin composite scaffolds for enhanced vascularized bone regeneration

丝素 脚手架 生物医学工程 化学 明胶 间充质干细胞 再生(生物学) 骨愈合 脐静脉 材料科学 细胞生物学 解剖 丝绸 体外 医学 生物化学 复合材料 生物
作者
Yang Jin,Changxu Deng,Muhammad Shafiq,Zhihui Li,Qianqian Zhang,Haibo Du,Shikai Li,Xiaojun Zhou,Chuanglong He
出处
期刊:Smart materials in medicine [Elsevier BV]
卷期号:3: 217-229 被引量:41
标识
DOI:10.1016/j.smaim.2022.01.007
摘要

Three-dimensional (3D) printing can construct products with accurate complex architecture. Engineered bone tissues that can promote vascularization and regulate directed differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) are considered as an ideal substitute the healing of bone for bone defects treatment. Herein, we fabricated a 3D printed BMSCs-laden scaffold using methacrylated gelatin and methacrylated silk fibroin (GelMA/SFMA) based bioinks along with localized sustained release of a small molecule drug fingolimod (FTY-720) for the synergistic interactions of vascularization and osteogenesis during bone repair. The GelMA/SFMA bioink showed significant advantages due to their tunable rheology, rapid thermal crosslinking, and improved shape fidelity following bioprinting. The in vitro experiments demonstrated that high cell viability of cells-laden constructs, while FTY-720-containing scaffolds significantly promoted migration and induced tube-like structure formation of human umbilical vein endothelial cells (HUVECs) as well as expressed high osteogenic-related genes expression of BMSCs. The implantation in a critical-size rat cranial defect model further revealed that FTY-720-loaded scaffolds significantly promoted vascularization and bone regeneration. Furthermore, scaffolds carrying BMSCs and FTY-720 were more osteogenic in vivo than scaffolds carrying BMSCs alone. Therefore, the constructed BMSCs-laden and FTY-720-loaded GelMA/SFMA scaffolds would be an ideal candidate with required structure and desired function for vascularization of bone regeneration.
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