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

Q1 Engineering
Jin Yang , Changxu Deng , Muhammad Shafiq , Zhihui Li , Qianqian Zhang , Haibo Du , Shikai Li , Xiaojun Zhou , Chuanglong He
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引用次数: 15

Abstract

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.

Abstract Image

3D打印细胞明胶/丝素复合支架的FTY-720局部递送,增强血管化骨再生
三维(3D)打印可以构建具有精确复杂结构的产品。工程骨组织能够促进血管化和调节骨髓间充质干细胞(BMSCs)的定向分化,被认为是骨愈合治疗骨缺损的理想替代品。在此,我们使用甲基丙烯酸明胶和甲基丙烯酸丝素(GelMA/SFMA)为基础的生物墨水,以及小分子药物fingolimod (FTY-720)的局部持续释放,制造了一个3D打印的bmscs负载支架,用于骨修复过程中血管化和成骨的协同相互作用。GelMA/SFMA生物链接具有显著的优势,因为它们具有可调的流变性、快速的热交联和生物打印后提高的形状保真度。体外实验表明,载细胞构建体具有较高的细胞活力,而含fty -720的支架可显著促进人脐静脉内皮细胞(HUVECs)的迁移和诱导管状结构的形成,并表达BMSCs的高成骨相关基因表达。在临界尺寸大鼠颅骨缺损模型中植入fty -720进一步表明,负载fty -720支架可显著促进血管形成和骨再生。此外,携带BMSCs和FTY-720的支架在体内比单独携带BMSCs的支架具有更强的成骨性。因此,构建的bmscs负载和fty -720负载的GelMA/SFMA支架将是具有骨再生血管化所需结构和功能的理想候选材料。
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来源期刊
Smart Materials in Medicine
Smart Materials in Medicine Engineering-Biomedical Engineering
CiteScore
14.00
自引率
0.00%
发文量
41
审稿时长
48 days
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