Optical solutions for large size-high resolution scaffolds fabrication

Bioprinting has emerged as a fabrication technique with wide acceptance in the field of tissue engineering due to its flexible 3D fabrication frame-work, high resolution and variety of available biocompatible materials.These capabilities have facilitated tissue engineering in the study and development of regenerative tissue models, through the fabrication of engineered scaffolds with complex pores patterning, pore’s interconnectivity and high repeatability.

However, bioprinting methods are typically limited by their printing speeds and sizes. These drawbacks clearly affect their range of application in practical medical care. One highly relevant example is the fabrication of tailored skin substitutes. With more than 60 commercial skin substitutes in the market and a still growing research interest, skin substitutes become an important target application for bioprinting technologies. The characteristics that make skin substitutes challenging to manufacture include: i) large areas (skin wounds can readily surpass 800cm2). ii)Flexible thicknesses (skin substitutes should be adapted into the different morphology of each wound). iii) High vascularization and porosity to promote cell’s migration, differentiation and proliferation. However, with building areas that barely exceed 4cm2, current bioprinting devices do not meet all the requirements of common regenerative medicine applications.

This thesis investigates and proposes alternative optical solutions beyond commonly used digital light processing (DLP) and stereolithography (SLA) technologies. The aim is to demonstrate precise voxel shaping while producing large-area exposures in a short time. This large-area constructs can be accomplished with the proposed light-sheet stereolithography (LS-SLA) method based on vat-photopolymerization (VP), experimentally validated through a built prototype using only off-the-shelf optical components. The LS-SLA prototype proves that the fabrication of centimeter-sized scaffolds with micrometer constructs are technically viable. In addition, LS-SLA provides the framework to print tailored skin substitutes with high vascularization and porosity as required in targeted regenerative medicine applications.

The work on the first prototype has triggered two research activities:(1) freeform optical design to tap the full potential of beam shaping optics. In LS-SLA, the optimization of freeform optics led to low energy losses and tailored uniform irradiances that enhance the accuracy and resolution of the structures. Moreover, the simulations showed that the propose ddesign method applies to many other state-of-the-art illumination and laser beam shaping problems. (2) Stock lenses finding for scan lenses generation. Off-the-shelf optical singlets reduce optical system cost,leading to wider accessibility of VP technologies in a future of tailored tissue fabrication. The combinatorial optimization to generate high-throughput low-cost scan lenses using off-the-shelf singlets is solved with an evolution strategy. The proposed meta-heuristic method proves an efficient solution for an unresolved optical design problem.

In summary, the main contributions of this thesis are (1) developing two computational design solutions for two challenging optical design problems, and (2) demonstrating the principles and technical viability of LS-SLA with a prototype for tissue engineering applications.