Speaker
Description
Introduction:
Replicating physiologically relevant tissue environments in vitro requires both sophisticated biological design and reliable scalable fabrication. Current approaches often rely on complex biofabrication methods such as stereolithography (SLA) and melt electrowriting (MEW), which are time-intensive, laborious, and lack reproducibility at scale [1,2]. To overcome these limitations, we developed a vascularized in vitro platform that integrates microchannel networks with industrial manufacturing methods, enabling reproducibility, scalability, and ease of use.
Methods:
The platform incorporates sacrificial template structures embedded within a biocompatible matrix. The dissolution of the template unveils a fully interconnected, perfusable microchannel network within the matrix for seeding with endothelial cells (ECs). This vascular network supports dynamic perfusion from the onset of cell culture, promoting long-term cell viability and tissue development. We transitioned from SLA and MEW to injection molding and vacuum casting, respectively to facilitate large-scale production. Injection molding was used to fabricate precise housing and structural components, while vacuum casting enabled flexible production of complex sacrificial template geometries using biocompatible materials.
Results:
The manufactured platforms demonstrated high reproducibility in microchannel geometry and structural fidelity across batches. Perfusable vascular networks were successfully formed following template dissolution, allowing for continuous media perfusion throughout the culture period. In preliminary cultures, embedded endothelial cells exhibited sustained viability and functionality throughout the entire culture period as confirmed by immunofluorescence staining and permeability assay, respectively. The perfusion system has the potential to enable controlled delivery of compounds, providing a platform for future physiologically relevant drug testing scenarios. Preliminary throughput assessments showed a significant reduction in production time and cost compared to SLA/MEW-based methods, with consistent device quality and usability.
Discussion:
Transitioning to industrial-grade manufacturing significantly improves the scalability of our in vitro system via enhanced reproducibility and reduced costs without compromising biological performance. The integration of injection molding and vacuum casting enables the creation of a ready-to-use, vascularized platform compatible with standard lab workflows. This approach addresses a critical bottleneck in tissue model development by aligning complex biological function with manufacturability. Future work will expand platform adaptability to other tissue types and perfusion modalities, further enhancing its value for pharmaceutical and academic research.
References:
[1] Mieszczanek, P., Corke, P., Mehanian, C. et al. Towards industry-ready additive manufacturing: AI-enabled closed-loop control for 3D melt electrowriting. Commun Eng 3, 158 (2024).
[2] Z. Wang, S. M. Mithieux, A. S. Weiss, Fabrication Techniques for Vascular and Vascularized Tissue Engineering. Adv. Healthcare Mater. 2019, 8, 1900742.
Acknowledgements:
The authors thank the Horizon EIC Transition project Vasc-on-Demand (project number 101156395) for financial support.
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