Serpe Federico, Iafrate Lucia, Bastioli Marco, Marcotulli Martina, Sanchini Caterina, De Turris Valeria, D'Orazio Michele, Palmisano Biagio, Mencattini Arianna, Martinelli Eugenio, Riminucci Mara, Casciola Carlo Massimo, Ruocco Giancarlo, Scognamiglio Chiara, Cidonio Gianluca
Italian Institute of Technology Center for Life Nano- & Neuro-Science, Viale Regina Elena 291, Rome, Rome, RM, 00161, ITALY.
Italian Institute of Technology Center for Life Nano- & Neuro-Science, Viale Regina Elena 291, Rome, Roma, RM, 00161, ITALY.
Biofabrication. 2025 Jul 23. doi: 10.1088/1758-5090/adf35b.
The advent of 3D bioprinting has revolutionised tissue engineering and regenerative medicine (TERM). Today, tissues of single cell type can be fabricated with extreme resolution and printing fidelity. However, the ultimate functionality of the desired tissue is limited, due to the absence of a multicellular population and diversity in micro-environment distribution. Currently, 3D bioprinting technologies are facing challenges in delivering multiple cells and biomaterials in a controlled fashion. The use of interchangeable syringe-based systems has often favoured the delamination between interfaces, greatly limiting the fabrication of interconnected tissue constructs. Microfluidic-assisted 3D bioprinting platforms have been found capable of rescuing the fabrication of tissue interfaces, but often fails to guarantee printing fidelity, cell density control and compartmentalisation. Herein, we present the convergence of microfluidic and 3D bioprinting platforms into a deposition system capable of harnessing a microfluidic printhead for the continuous rapid fabrication of interconnected functional tissues. The use of flow-focusing and passive mixer printhead modules allowed for the rapid and dynamic modulation of fibre diameter and material composition, respectively. Cells were compartmentalised into discrete three-dimensional layers with defined density patterns, confirming the punctual control of the presented microfluidic platform in arranging cells and materials in 3D. In ovo and in vivo studies demonstrated the seminal functionality of 3D bioprinted constructs with patterned vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1), respectively. This, in turn, facilitated the simulation of diverse cellular environments and proliferation pathways within a single construct, which is currently unachievable with conventional 3D bioprinting techniques, offering new opportunities for the fabrication of functionally graded systems and physiologically-relevant skeletal tissue substitutes.
3D生物打印技术的出现彻底改变了组织工程与再生医学（TERM）。如今，单一细胞类型的组织能够以极高的分辨率和打印精度制造出来。然而，由于缺乏多细胞群体以及微环境分布的多样性，所期望组织的最终功能受到限制。目前，3D生物打印技术在以可控方式输送多种细胞和生物材料方面面临挑战。基于可互换注射器的系统的使用常常导致界面之间出现分层，极大地限制了相互连接的组织构建体的制造。已发现微流体辅助的3D生物打印平台能够挽救组织界面的制造，但往往无法保证打印精度、细胞密度控制和分隔。在此，我们展示了微流体和3D生物打印平台融合成一种沉积系统，该系统能够利用微流体打印头连续快速制造相互连接的功能性组织。流动聚焦和被动混合器打印头模块的使用分别实现了纤维直径和材料成分的快速动态调制。细胞被分隔成具有确定密度模式的离散三维层，证实了所展示的微流体平台在三维空间中排列细胞和材料方面的精确控制。卵内和体内研究分别证明了具有图案化血管内皮生长因子（VEGF）和转化生长因子-β1（TGF-β1）的3D生物打印构建体的开创性功能。这反过来又促进了在单个构建体内模拟多种细胞环境和增殖途径，而这是传统3D生物打印技术目前无法实现的，为制造功能梯度系统和生理相关的骨骼组织替代物提供了新机会。
