Laser-based subtractive manufacturing for tissue engineering

Clinical 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 the vascularization of tissue engineered constructs.

In this work, we developed a multistep patterning method to precisely create hierarchical vascular trees using a commercial 355 nm laser ablation system. In 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]. 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. Subsequently, 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., velocity, beam intensity, z-step, etc.) was required to precisely reproduce the 3D CAD model within a diversity of low stiffness hydrogels.

The resulting vascular trees can be used to obtain capillary beds for tissue engineering applications and the developed method can be adapted to a multitude of other applications exploiting transparent hydrogel scaffolds.

Acknowledgements

EU Horizon 2020 research and innovation programme under the ERC grant CapBed (805411), IF/00347/2015

[1]       A. A. Guy, A. W. Justin, D. M. Aguilar-Garza, and A. E. Markaki, “3D Printable Vascular Networks Generated by Accelerated Constrained Constructive Optimization for Tissue Engineering,” IEEE Trans. Biomed. Eng., pp. 1–1, 2019.