Hydrogels are a class of polymeric soft materials with a three-dimensional (3D) crosslinked hydrophilic network structure, which possess the softness and high water content of natural tissues. They offer advantages over other synthetic biomaterials in simulating natural living tissues. In conventional approaches, ultraviolet (UV)-band single-photon beams are used for mode transitions in hydrogels.

However, these approaches often fall short in terms of penetration depth and resolution, failing to meet the experimental expectations. In emerging methods, two-photon excitation of hydrogel materials using ultrafast lasers in the near-infrared band can improve the spatial and temporal resolution of hydrogels in various response states. However, these methods provide only single results for hydrogels and lack of multimodal processing capabilities, thereby limiting the application scenarios for hydrogels. In this study, we combine femtosecond laser direct-write micro/nano-processing with multiple optical response states of hydrogels. We propose a multimodal processing method for hydrogel materials that realizes the bimodal processing of laser additive?removal for the same hydrogel. This processing scheme can create more diverse hydrogel environments through multimodal manipulation of different states of same hydrogel material, offering considerable potential for applications in simulating various biological tissue constructions and in vitro cell culture.

In this study, a femtosecond laser system with an 800 nm wavelength, 100 fs pulse width, and 80 MHz repetition frequency was used. The laser spot diameter ranged from 1 to 2 μm. This system used multiphoton effects to induce photopolymerization and photoablation in a gelatin methacrylate (GelMA) hydrogel, thereby enabling polymerization and the removal of custom channels during the formation of 3D structures. During the laser addition process, methacrylic anhydride was first introduced into the hydrogel precursor mixture to facilitate light curing. A femtosecond laser was focused within the GelMA hydrogel pre-fluid, triggering photopolymerization. The monomer molecules absorbed two photons, forming multichain polymers. For the laser removal process, the GelMA hydrogel was first cured using UV light. In particular, the femtosecond laser’s high energy density induced photochemical and photothermal reactions in the hydrogel. By optimizing the processing parameters, we controlled the temperature and pressure in the ablation region, generating cavitation bubbles. These bubbles expelled the waste material produced during photoablation and ultimately allowed the creation of the desired microchannel structures.

Results demonstrate that by fine-tuning key parameters, such as laser energy density, spot dwell time, and scanning mode, the photopolymerization and photoablation processes can be precisely controlled. These adjustments have minimal interference with the surrounding environment. As shown in Fig. 3, the GelMA hydrogels formed via femtosecond laser direct-write polymerization have high resolution and cleanliness. This allows for the precise formation of customized 3D structures. By adjusting the crosslink spacing, we can obtain different crosslinking patterns, such as row-resolved crosslinking with high separation, surface-resolved crosslinking with medium aggregation, and smooth-body crosslinking with high aggregation. These different crosslinking arrangements provide flexibility in designing the mechanical properties and spatial organization of the materials. Figure 5 illustrates the successful fabrication of the microchannel structures removed by the laser from a GelMA hydrogel sample that has undergone UV crosslinking curing. These microchannels vary in length, diameter, and shape, illustrating the ability of femtosecond laser processing techniques to enable highly accurate and versatile channel designs. The successful fabrication of the complex customized structures further highlights the broad applicability and potential of this approach.

In this study, we proposed an innovative femtosecond laser-based multimodal processing scheme for the microscale and nanoscale processing of hydrogels. The proposed scheme is highly designable and precise. By modifying the existing mixture of photosensitive hydrogel precursors and photoinitiators, we created a hydrogel processing pre-fluid with a light-curing property. By changing a series of parameters, such as femtosecond laser power, spot residence time, and scanning mode, photocrosslinking additive and photoablation removal modes can be effectively implemented using the proposed femtosecond laser processing scheme. Through careful control of dwell time and scanning line spacing, it is possible to fabricate row-resolved crosslinked, surface-resolved crosslinked, and smooth-body crosslinked hydrogel structures with minimal disturbance to the surrounding material. By integrating computer programs for processing customized structures and exporting processing files, laser additive manufacturing of various 3D structures can be achieved, enhancing fabrication precision. The photoablation removal experiments can also be performed on the hydrogel precured with UV light by flexibly adjusting the laser power and scanning times of the femtosecond laser. The resulting microchannels show excellent adjustability and flexibility in the dimensions of length, diameter, and shape. In summary, the proposed method achieves multimodal processing of a hydrogel and customizes the target structure of the hydrogel under the action of light, opening up considerable possibilities for applications in in vitro cell culture, tissue simulation, and other cutting-edge biomedical fields.