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用于先进组织工程气管的混合 3D 生物打印:融合熔丝制造(FDM)和自上而下数字光处理(DLP)。

Hybrid 3D bioprinting for advanced tissue-engineered trachea: merging fused deposition modeling (FDM) and top-down digital light processing (DLP).

机构信息

Nano-Bio Regenerative Medical Institute, College of Medicine, Hallym University, Chuncheon, 24252, Republic of Korea.

Institute of New Frontier Research Team, Hallym University, Hallym Clinical and Translation Science Institute, Chuncheon 24252, Republic of Korea.

出版信息

Biofabrication. 2024 Nov 21;17(1). doi: 10.1088/1758-5090/ad92da.

DOI:10.1088/1758-5090/ad92da
PMID:39541729
Abstract

In this present study, we introduce an innovative hybrid 3D bioprinting methodology that integrates fused deposition modeling (FDM) with top-down digital light processing (DLP) for the fabrication of an artificial trachea. Initially, polycaprolactone (PCL) was incorporated using an FDM 3D printer to provide essential mechanical support, replicating the structure of tracheal cartilage. Subsequently, a chondrocyte-laden glycidyl methacrylated silk fibroin hydrogel was introduced via top-down DLP into the PCL scaffold (PCL-Sil scaffold). The mechanical evaluation of PCL-Sil scaffolds showed that they have greater flexibility than PCL scaffolds, with a higher deformation rate (PCL-Sil scaffolds: 140.9% ± 5.37% vs. PCL scaffolds: 124.3% ± 6.25%) and ability to withstand more force before fracturing (3.860 ± 0.140 N for PCL-Sil scaffolds vs. 2.502 ± 0.126 N for PCL scaffolds, ***< 0.001). Both types of scaffolds showed similar axial compressive strengths (PCL-Sil scaffolds: 4.276 ± 0.127 MPa vs. PCL scaffolds: 4.291 ± 0.135 MPa). Additionally, PCL-Sil scaffolds supported fibroblast proliferation, indicating good biocompatibility.testing of PCL-Sil scaffolds in a partial tracheal defect rabbit model demonstrated effective tissue regeneration. The scaffolds were pre-cultured in the omentum for two weeks to promote vascularization before transplantation. Eight weeks after transplantation into the animal, bronchoscopy and histological analysis confirmed that the omentum-cultured PCL-Sil scaffolds facilitated rapid tissue regeneration and maintained the luminal diameter at the anastomosis site without signs of stenosis or inflammation. Validation study to assess the feasibility of our hybrid 3D bioprinting technique showed that structures, not only the trachea but also the vertebral bone-disc and trachea-lung complex, were successfully printed.

摘要

在本研究中,我们介绍了一种创新的混合 3D 生物打印方法,该方法将熔融沉积建模(FDM)与自上而下的数字光处理(DLP)相结合,用于制造人工气管。首先,使用 FDM 3D 打印机将聚己内酯(PCL)掺入其中,以提供必要的机械支撑,复制气管软骨的结构。随后,通过自上而下的 DLP 将载有软骨细胞的甲基丙烯酰化丝素蛋白水凝胶引入到 PCL 支架(PCL-Sil 支架)中。PCL-Sil 支架的机械评估表明,与 PCL 支架相比,它们具有更大的灵活性,变形率更高(PCL-Sil 支架:140.9%±5.37% vs. PCL 支架:124.3%±6.25%),在断裂前能承受更大的力(PCL-Sil 支架:3.860±0.140 N vs. PCL 支架:2.502±0.126 N,***<0.001)。两种类型的支架都具有相似的轴向压缩强度(PCL-Sil 支架:4.276±0.127 MPa vs. PCL 支架:4.291±0.135 MPa)。此外,PCL-Sil 支架支持成纤维细胞增殖,表明具有良好的生物相容性。在兔部分气管缺损模型中对 PCL-Sil 支架进行测试,结果表明其具有有效的组织再生能力。支架在移植前先用网膜预培养两周以促进血管生成。移植后 8 周,支气管镜和组织学分析证实,网膜培养的 PCL-Sil 支架促进了快速的组织再生,并保持吻合部位的管腔直径,没有狭窄或炎症的迹象。验证研究评估了我们的混合 3D 生物打印技术的可行性,结果表明不仅可以打印气管,还可以打印椎体-椎间盘和气管-肺复合体等结构。

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