Progress in the Application of China University of Science and Technology's Femtosecond Laser Processing Technology in the Biomedical Field

Recently, Associate Professor Li Jiawen's research group at the Micro and Nano Engineering Laboratory of the School of Engineering Science, University of Science and Technology of China proposed a femtosecond laser dynamic holographic processing method suitable for efficient construction of three-dimensional capillary scaffolds, which is used to generate a three-dimensional capillary network. This work was published in Advanced Functional Materials under the title "Rapid Construction of 3D Biometric Capital Networks with Complex Morphology Using Dynamic Holographic Processing" and was selected as a journal cover paper. The related technology has been granted a patent.

Femtosecond laser two-photon polymerization has nanoscale processing resolution and three-dimensional manufacturing capability, but traditional processing strategies have low efficiency in printing microvascular networks. Based on the previous work, the research group proposed a local phase modulation method to generate a circular notch light field on the basis of a circular Bessel beam. The rapidly changing notch ring light was exposed inside the photoresist, achieving efficient processing of complex morphology bifurcated microtubule networks and biomimetic multi hole microtubules. The processing speed was increased by more than 30 times compared to traditional point-to-point processing methods. The research team used a porous microtubule network as a scaffold to guide endothelial cell adhesion and growth, achieving the construction of a complex microvascular network with defined morphology. This work will provide a platform for research in the fields of tissue engineering, drug screening, and vascular physiology. Master's student Song Bowen, doctoral student Fan Shengying, and postdoctoral fellow Wang Chaowei from the School of Engineering Sciences are the co first authors of the paper, and Li Jiawen is the corresponding author.

Efficient construction method for microvascular network: (a) Schematic diagram of dynamic holographic efficient processing; (b) Bifurcated microtubules; (c) Endothelial cells on the surface of microtubules

In recent years, Li Jiawen's research group has actively explored the application of femtosecond laser processing technology in the biomedical field, and has made progress in the preparation methods of micro and nano robots. Micro/nano robots have shown great application prospects in the biomedical field. In order to realize the mass preparation and controllable transportation of micro robots in complex environments, the research group proposed an efficient preparation method of environment responsive micro spiral robots based on rotating dynamic holographic light field, which can process thousands of hydrogel micro spiral robots in 0.5 h. The robot achieves intelligent adaptive deformation of its own morphology under pH regulation, and then undergoes multiple motion modes under magnetic field drive, achieving targeted drug transportation (ACS Nano 2021, 1518048; Light: Adv. Manufacturing 2023, 4:29). In order to solve the problem of low magnetic content and small driving force of micro spiral robots, which are difficult to overcome the influence of environmental flow velocity, the research group proposes a pure nickel spiral micro robot prepared based on two-photon polymerization forming and sintering process. The magnetic content of the spiral robot is about 90wt%, and it enhances the magnetic torque under low intensity rotating magnetic field. The maximum speed can reach 12.5 body lengths per second, and it can push objects 200 times heavier than itself, And maintain controlled motion in the fluid (Lab Chip, 2024, DOI: 10.1039/d3lc01084h).

Fig. Micro nano spiral robot: (a) efficient preparation and environmental response characteristics of hydrogel micro nano robot; (b) Micro nano metal robots can overcome the influence of flow velocity.

In addition, Li Jiawen's research group explored the influence of micro nano structures on neuronal growth behavior based on femtosecond laser two-photon processing technology. They collaborated with Professor Bi Guoqiang from the Department of Life Medicine and Associate Professor Ding Weiping from the School of Information Science and Technology to prepare patterned micro column arrays with different spacing and height using femtosecond two-photon technology. They found that neuronal axons tended to grow on equal height micro columns, and by constructing micro column arrangements, they could guide neuronal directional growth and form neural circuits (Adv. Healthcare Mater2021, 102100094). Inspired by the myelin sheath of axons, the joint research team designed and prepared microtubule structures with different diameters, wall thicknesses, and lengths to simulate the myelin sheath of axons. It was found that microtubule structures can accelerate the growth rate of nerve axons (more than 10 times). In addition, the joint research team sputtered magnetic thin films of nickel and biocompatible thin films of titanium on the surface of microtubules. Under external magnetic field manipulation, the magnetic microtubules can be used for precise connection of neurons, thus forming specific biological neural circuits (Nano Lett., 2022, 22:8991). Micro nano structures can achieve directed and accelerated growth of neurons, providing methods and ideas for directed connection of separated neural clusters, neural network construction, and rapid repair of neural damage.

The effect of micro nano structure on neuronal axon growth: (a) neuronal axons grow directionally along micro columns of the same height; (b) Porous microtubules can accelerate the growth of neuronal axons and achieve directional connections of neurons.
The above research work has been supported by the National Natural Science Foundation of China, the Key R&D Program of the Ministry of Science and Technology, and the Anhui Province Science and Technology Major Research Projects.

Source: University of Science and Technology of China