Laser-based subtractive manufacturing for tissue engineering

Jun 30, 2022, 12:20 PM
10m
Room: S1

Room: S1

Speaker

Cruz-Moreira, Daniela (3B’s Research Group, I3BS – Research Institute on Biomaterials, Biodegradables and Biomimetics, ICVS/3B’s - PT Government Associate Laboratory, University of Minho)

Description

"Introduction
linical translation of tissue engineering-based therapies is currently limited by the difficulty in inducing essential vascularisation for tissue viability after transplantation. Thick and metabolically demanding engineered tissues require a defined microvascular network to provide sufficient nutrient and gas exchange. Laser ablation has emerged as a promising technology to fabricate custom-made perfusable microfluidic channels that mimic capillary beds and aid both anastomosis and vascularization of tissue engineered constructs. So far, the proposed laser-driven methods use expensive laser systems or involve heavy in house customization. In this work, we developed a multistep patterning method to precisely create hierarchical vascular trees using a commercial, affordable and widely available 355 nm laser ablation system.

Methodology
n order to design physiologically relevant capillary networks that consider tissue geometry, physical constraints, and structure stability, vascular trees were generated using a constrained constructive optimization-based method [1]. More particularly, vascular trees were generated using Accelerated Constrained Constructive Optimization as arterial/venous matched pairs meeting at simple anastomoses. Batch optimization was used to minimize a combination of network volume and pump work, with post-build bifurcation asymmetry correction. Inter- and intra-network collisions were resolved, including padding to ensure vessel spacing. Vessels were smoothed and new collisions resolved before export. A Zeiss/Rapp-Opto commercially available laser ablation system was then used. A slicing and tiling algorithm was developed to bridge the gap between 3D CAD model and laser software specific formats. Also, an optimization of the working parameters of laser manufacturing tools (e.g., beam intensity, z-step, overlap, etc.) was required to precisely reproduce the 3D CAD model within a diversity of low stiffness hydrogels.

Results
Ablated features were sliced, imaged and measured through light microscopy. Channels were perfused with 2µm fluorescent beads or injected with commercial silicone rubber and were assessed through confocal microscopy or micro computed tomography, respectively. Complete ablation and formation of open lumen were achieved. Networks of different dimensions created through constrained constructive optimization– including networks larger than the objective were successful recreated. Precise control down to 10µm in resolution was also reported.

Conclusions
In conclusion, this work provides an efficient tool to create customized hollow networks within transparent hydrogel scaffolds in an automated manner. The resulting vascular trees can be used to obtain capillary beds for tissue engineering applications and the development method can be adapted to a multitude of other bio- inspired systems.

Acknowledgements
EU Horizon 2020 research and innovation programme under the ERC grant CapBed (805411), IF/00347/2015 and FCT (S. Queirós, CEECIND/03064/2018).

References
1. Guy, A. A. et al., IEEE Trans. Biomed. Eng. 67, 1650-1663 (2019)"
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