摘要
水凝胶尤其是蛋白质大分子水凝胶的飞秒激光微纳加工,可以实现真三维、低损伤和多样功能化等特性,在人工微生理环境构建、片上器官及其互连、再生医学等领域具有较大的应用潜力。基于多光子效应,本工作通过引发甲基丙烯酸化胶原蛋白的光交联或光消融双模态物态变化,实现了其水凝胶三维结构的微纳打印及其内部沟道的微纳直写,为体外片上细胞和组织微环境模拟等提供了一种新技术。
Objective Hydrogels are a class of polymeric soft materials with a threedimensional(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 singlephoton 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,twophoton excitation of hydrogel materials using ultrafast lasers in the nearinfrared 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 directwrite micro/nanoprocessing 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.Methods 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 2μm.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 prefluid,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 and Discussions Results demonstrate that by finetuning 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 directwrite 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 rowresolved crosslinking with high separation,surfaceresolved crosslinking with medium aggregation,and smoothbody 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.Conclusions In this study,we proposed an innovative femtosecond laserbased 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 prefluid with a lightcuring 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 rowresolved crosslinked,surfaceresolved crosslinked,and smoothbody 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 cuttingedge biomedical fields.
作者
刘赟
黄瀚轩
肖子峰
闫勇军
郑勋仁
孙允陆
Liu Yun;Huang Hanxuan;Xiao Zifeng;Yan Yongjun;Zheng Xunren;Sun Yunlu(School of Information Science and Technology,Fudan University,Shanghai 200082,China;Department of Mechanical and Automation Engineering,the Chinese University of Hong Kong,Hong Kong 999077,China)
出处
《中国激光》
北大核心
2025年第8期307-313,共7页
Chinese Journal of Lasers
基金
上海市浦江人才计划(22PJD008)
国家自然科学基金(62475046)。
关键词
飞秒激光微纳加工
双光子吸收
光交联
光消融
水凝胶微纳结构
femtosecond laser micro/nanofabrication
twophoton absorption
photocrosslinking
laser ablation
hydrogel micro/nanostructure
