3D printing technology has attracted much attention due to its high potential in scientific and industrial applications. As an outstanding 3D printing technology, two-photon polymerization (TPP) microfabrication has been applied in the fields of micro/nanophotonics, micro-electromechanical systems, microfluidics, biomedical implants and microdevices. In particular, TPP microfabrication is very useful in tissue engineering and drug delivery due to its powerful fabrication capability for precise microstructures with high spatial resolution on both the microscopic and the nanometric scale. The design and fabrication of 3D hydrogels widely used in tissue engineering and drug delivery has been an important research area of TPP microfabrication. The resolution is a key parameter for 3D hydrogels to simulate the native 3D environment in which the cells reside and the drug is controlled to release with optimal temporal and spatial distribution in vitro and in vivo. The resolution of 3D hydrogels largely depends on the efficiency of TPP initiators. In this paper, we will review the widely used photoresists, the development of TPP photoinitiators, the strategies for improving the resolution and the microfabrication of 3D hydrogels.

Hydrogels with a precise 3D configuration (3D hydrogels) are required for a number of biomedical applications such as tissue engineering and drug delivery. Two-photon polymerization (TPP) is an advanced method to fabricate 3D hydrogels. However, TPP of 3D hydrogels has been challenged by the lack of TPP initiators with high efficiency in aqueous medium. In this study, a water soluble TPP initiator (WI) with high fabrication efficiency was prepared by combining hydrophobic 2,7-bis(2-(4-pentaneoxy-phenyl)-vinyl)anthraquinone (N) with a C_2v symmetrical structure and 2-hydroxypropyl-β-cyclodextrins through host–guest chemical interaction. Both one and two-photon optical properties of WI have been investigated. In aqueous medium, WI showed a two-photon absorption cross-section of around 200 GM at the wavelength of 780 nm which was much higher compared with those of commercial initiators. The threshold energy of TPP for the resin with WI as a photoinitiator (the molar ratio of N in resin is 0.03%) was 8.6 mW. 3D hydrogels with a woodpile microstructure were further fabricated by using an average power of 9.7 mW and a scanning speed of 30 μm s⁻¹.

Hydrogels with precise 3D configuration (3D hydrogels) are crucial for biomedical applications such as tissue engineering and drug delivery, which require the improvement of the spatial resolution on both the microscopic and the nanometric scale. In this study, a water soluble two-photon polymerization (TPP) initiator (WI) with high initiating efficiency was prepared by using a poloxamer (PF127) to encapsulate 2,7-bis(2-(4-pentaneoxy-phenyl)-vinyl)anthraquinone via a hydrophilic–hydrophobic assembly. The threshold energy for WI was 6.29 mW at a linear scanning speed of 10 μm s⁻¹, which was much lower than those reported previously. A lateral spatial resolution of 92 nm was achieved as the resolution breakthrough of 3D hydrogels. Finally, the microstructure with high accuracy simulating the morphology of adenovirus was fabricated at the laser power close to the threshold energy of TPP, further demonstrating the ultrahigh resolution of 3D hydrogels.