Speaker
Description
Introduction
Tissue engineering aims to develop functional tissues for regenerative medicine. To achieve this, vascularization is essential, particularly in thick constructs where diffusion alone is insufficient. Neural tissues are especially challenging due to their high metabolic needs and reliance on dense vascular networks1. Although recent strategies have attempted to recreate vascularized environments in vitro, conventional bioprinting techniques still lack precise spatial control and multi-material integration. Microfluidic bioprinting addresses these limitations by enabling real-time control of material flow and composition, allowing the fabrication of tailored fibers.
To overcome these limitations, we developed a dual-innovation strategy combining (i) core–shell hydrogel fiber bioprinting using separate biomaterial formulations optimized for neural and endothelial compartments, and (ii) a vessel-inspired structural design integrated into a custom perfusable bioreactor. This system enables the fabrication of compact, brain-like tissues incorporating a vessel, paving the way towards the development of a blood-brain barrier (BBB) model.
Methods
Two distinct hydrogel inks were formulated: a soft bioink for neural tissue and a stiffer endothelial bioink composed of gelatin and human placenta-derived decellularized extracellular matrix (dECM). A custom microfluidic printhead enabled continuous extrusion of core–shell fibers where the softer neural compartment was surrounded by a stiffer endothelial ring. By adjusting the inner and outer flow rates, we achieved controlled fiber architecture and stable long-term culture despite the softness of the neural ink, generating microarchitectures that improved cellular organization and compactness2.
The printed fibers were arranged in a computer-aided compact vessel and integrated into a custom bioreactor for dynamic perfusion. Varying perfusion rates were applied to generate different shear stress levels on the inner surface of the printed compact vessel to promote endothelial alignment on the shell of each fiber. Structural integrity, compartmentalization, barrier function, and cell viability and morphology were assessed by fluorescence imaging.
Results
The microfluidic printhead enabled the fabrication of two distinct fiber architectures: core–shell and sandwich. In core–shell fibers, the neural ink was encapsulated by the endothelial shell, while in sandwich fibers the two materials were layered side by side. Adjusting flow rates allowed control over geometry and neural-to-endothelial area ratios.
Both structures maintained integrity during perfusion and supported endothelial alignment and barrier-like formation under flow. Neural cells preserved viability and morphology. These results show that 3D microfluidic bioprinting offers a valuable platform to engineer a neurovascular unit.
Discussion
This platform enables the bioprinting of compact, perfusable vessel surrounded by neural tissue. Microfluidic tuning of fiber architecture allowed optimization of both form and function, while shear stress promoted endothelial organization. The approach offers a versatile foundation for generating dynamic neurovascular models.
Future work will aim to validate long-term tissue maturation under flow and extend the platform for BBB modeling by incorporating microvascular endothelial cells, astrocytes, and pericytes. This strategy addresses the limitations of static culture systems and advances the development of physiologically relevant models for disease research and drug testing, aligning with the conference’s vision for transformative biofabrication.
References
[1] Haase K. et al., Nat. Biomed. Eng., 2023.
[2] Serpe F. et al., Int. J. Bioprint., 2024.
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