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Abstract Advances in biofabrication have enabled the generation of freeform perfusable networks mimicking vasculature. However, key challenges remain in the effective endothelialization of these complex, vascular-like networks, including cell uniformity, seeding efficiency, and the ability to pattern multiple cell types. To overcome these challenges, we present an integrated fabrication and endothelialization strategy to directly generate branched, endothelial cell-lined networks using a diffusion-based, embedded 3D bioprinting process. In this strategy, a gelatin microparticle sacrificial ink delivering both cells and crosslinkers is extruded into a crosslinkable gel precursor support bath. A self-supporting, perfusable structure is formed by diffusion-induced crosslinking, after which the sacrificial ink is melted to allow cell release and adhesion to the printed lumen. This approach produces a uniform cell lining throughout networks with complex branching geometries, which are challenging to uniformly and efficiently endothelialize using conventional perfusion-based approaches. Furthermore, the biofabrication process enables high cell viability (>90%) and the formation of a confluent endothelial layer providing vascular-mimetic barrier function and shear stress response. Leveraging this strategy, we demonstrate for the first time the patterning of multiple endothelial cell types, including arterial and venous cells, within a single arterial–venous-like network. Altogether, this strategy enables the fabrication of multi-cellular engineered vasculature with enhanced geometric complexity and phenotypic heterogeneity.
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Gelation of Uniform Interfacial Diffusant in Embedded 3D Printing
Abstract While the human body has many different examples of perfusable structures with complex geometries, biofabrication methods to replicate this complexity are still lacking. Specifically, the fabrication of self‐supporting, branched networks with multiple channel diameters is particularly challenging. Herein, the Gelation of Uniform Interfacial Diffusant in Embedded 3D Printing (GUIDE‐3DP) approach for constructing perfusable networks of interconnected channels with precise control over branching geometries and vessel sizes is presented. To achieve user‐specified channel dimensions, this technique leverages the predictable diffusion of cross‐linking reaction‐initiators released from sacrificial inks printed within a hydrogel precursor. The versatility of GUIDE‐3DP to be adapted for use with diverse physicochemical cross‐linking mechanisms is demonstrated by designing seven printable material systems. Importantly, GUIDE‐3DP allows for the independent tunability of both the inner and outer diameters of the printed channels and the ability to fabricate seamless junctions at branch points. This 3D bioprinting platform is uniquely suited for fabricating lumenized structures with complex shapes characteristic of multiple hollow vessels throughout the body. As an exemplary application, the fabrication of vasculature‐like networks lined with endothelial cells is demonstrated. GUIDE‐3DP represents an important advance toward the fabrication of self‐supporting, physiologically relevant networks with intricate and perfusable geometries.
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- PAR ID:
- 10441385
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Functional Materials
- Volume:
- 33
- Issue:
- 50
- ISSN:
- 1616-301X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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