Maggiotto Federico, Bova Lorenzo, Micheli Sara, Pozzer Camilla, Fusco Pina, Sgarbossa Paolo, Billi Fabrizio, Cimetta Elisa
Department of Industrial Engineering (DII), University of Padua, Padova, Italy.
Fondazione Istituto di Ricerca Pediatrica Città della Speranza (IRP), Padova, Italy.
Front Bioeng Biotechnol. 2025 Jan 29;13:1484738. doi: 10.3389/fbioe.2025.1484738. eCollection 2025.
The ever-growing need for improved models of human tissues to study both healthy and diseased states is advancing the use of techniques such as 3D Bioprinting. We here present our results on the development of a vascularized and perfusable 3D tumor mimic for studies of the early steps of Neuroblastoma metastatic spread. We used a multi-material and sacrificial bioprinting approach to fabricate vascularized 3D cell-laden structures and developed a customized perfusion system enabling maintenance of growth and viability of the constructs for up to 3 weeks. Cell phenotypes and densities in co-culture for both the bulk of the construct and the endothelialization of the vascular channels were optimized to better replicate conditions and ideally simulate tumor progression. We proved the formation of an endothelium layer lining the vascular channel after 14 days of perfused culture. Cells in the bulk of the construct reflected Neuroblastoma growth and its tendency to recruit endothelial cells contributing to neovascularization. We also collected preliminary evidence of Neuroblastoma cells migration towards the vascular compartment, recapitulating the first stages of metastatic dissemination.
对用于研究健康和疾病状态的改进型人体组织模型的需求不断增长，这推动了3D生物打印等技术的应用。我们在此展示了关于开发一种血管化且可灌注的3D肿瘤模型的研究结果，该模型用于研究神经母细胞瘤转移扩散的早期步骤。我们采用多材料和牺牲性生物打印方法来制造血管化的3D载细胞结构，并开发了一种定制的灌注系统，使构建体能够维持生长和活力长达3周。对构建体主体和血管通道内皮化的共培养中的细胞表型和密度进行了优化，以更好地复制条件并理想地模拟肿瘤进展。我们证明了在灌注培养14天后，血管通道内衬形成了内皮细胞层。构建体主体中的细胞反映了神经母细胞瘤的生长及其招募内皮细胞促进新血管形成的趋势。我们还收集了神经母细胞瘤细胞向血管腔迁移的初步证据，重现了转移扩散的第一阶段。
