Abstract

AbstractMicro/nano-fabrication technology via two-photon polymerization (TPP) nanolithography is a powerful and useful manufacturing tool that is capable of generating two dimensional (2D) to three dimensional (3D) arbitrary micro/nano-structures of various materials with a high spatial resolution. This technology has received tremendous interest in cell and tissue engineering and medical microdevices because of its remarkable fabrication capability for sophisticated structures from macro- to nano-scale, which are difficult to be achieved by traditional methods with limited microarchitecture controllability. To fabricate precisely designed 3D micro/nano-structures for biomedical applications via TPP nanolithography, the use of photoinitiators (PIs) and photoresists needs to be considered comprehensively and systematically. In this review, widely used commercially available PIs are first discussed, followed by elucidating synthesis strategies of water-soluble initiators for biomedical applications. In addition to the conventional photoresists, the distinctive properties of customized stimulus-responsive photoresists are discussed. Finally, current limitations and challenges in the material and fabrication aspects and an outlook for future prospects of TPP for biomedical applications based on different biocompatible photosensitive composites are discussed comprehensively. In all, this review provides a basic understanding of TPP technology and important roles of PIs and photoresists for fabricating high-precision stimulus-responsive micro/nano-structures for a wide range of biomedical applications.

Highlights

  • Well-defined three-dimensional (3D) structures with micro- or nano-features are of great interest for diverse bioapplications including cell engineering [1], tissue engineering [2,3], biorobots [4]. microfluidic systems [5] and drug delivery [6,7]

  • This review provides a basic understanding of two-photon polymerization (TPP) technology and important roles of PIs and photoresists for fabricating high-precision stimulus-responsive micro/nano-structures for a wide range of biomedical applications

  • Unlike conventional single-photon polymerization induced by an ultraviolet (UV) laser, a photoinitiator (PI) molecule in a polymerizable resist consisting of monomers or oligomers absorbs two photons simultaneously to initiate polymerization in a highly localized region around the center of the focused

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Summary

Introduction

Well-defined three-dimensional (3D) structures with micro- or nano-features are of great interest for diverse bioapplications including cell engineering [1], tissue engineering [2,3], biorobots [4]. microfluidic systems [5] and drug delivery [6,7]. A solid volume pixel, known as a voxel in micro/nano-fabrication, is created [13] Based on this voxel-by-voxel approach, sophisticated design features can be realized in specific areas of structures by a tightly focused laser beam without the need to use photomasks. Well-organized scaffolds fabricated by TPP can mimic the natural microenvironment of human tissue with respect to multi-scale structures They serve as a versatile platform to promote the regulation of cell behavior, including cell attachment, proliferation, differentiation and cell-to-cell interaction [36]. As PIs and photoresists play crucial roles in fabricating stimulus-responsive micro/nano-structures via TPP technology such as spatial resolution of the structures and their manufacturing time, currently widely used PIs and different photoresists are summarized systematically in terms of their properties and two-photon absorption capability. Current limitations and challenges in the material and fabrication aspects as well as the outlook on future prospects of TPP for biomedical applications are described

TPP PIs for biomedical applications
TPP-compatible photoresists
Ready-to-use commercially available photoresists for TPP
Customized smart materials for TPP
Light-responsive photoresists
Electromagnetic field-responsive photoresists
Cell engineering
Tissue engineering
Findings
Biomedical devices
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