Processing of materials by ultrashort laser pulses has evolved significantly over the last decade and is starting to reveal its scientific, technological and industrial potential. In ultrafast laser manufacturing, optical energy of tightly focused femtosecond or picosecond laser pulses can be delivered to precisely defined positions in the bulk of materials via two-/multi-photon excitation on a timescale much faster than thermal energy exchange between photoexcited electrons and lattice ions. Control of photo-ionization and thermal processes with the highest precision, inducing local photomodification in sub-100-nm-sized regions has been achieved. State-of-the-art ultrashort laser processing techniques exploit high 0.1–1 μm spatial resolution and almost unrestricted three-dimensional structuring capability. Adjustable pulse duration, spatiotemporal chirp, phase front tilt and polarization allow control of photomodification via uniquely wide parameter space. Mature opto-electrical/mechanical technologies have enabled laser processing speeds approaching meters-per-second, leading to a fast lab-to-fab transfer. The key aspects and latest achievements are reviewed with an emphasis on the fundamental relation between spatial resolution and total fabrication throughput. Emerging biomedical applications implementing micrometer feature precision over centimeter-scale scaffolds and photonic wire bonding in telecommunications are highlighted.

/pdf/ultrafast-laser-processing-of-materials-from-science-to-rducz2yjvs.pdf

Ultrafast laser processing of materials: from science to industry

Functional polymer surfaces for controlling cell behaviors

Fabrication technology for three-dimensional microstructures with submicrometer accuracy has been needed in the fields of modern optics, such as micro mechanical system driven with photon pressure[1, 2] and laser-trapping near-filed optical microscopy[3]. However, the present accuracy with stereolithography[4] is not yet satisfactory to this purpose. Moreover, it is not so flexible to make a three- dimensional structure with the present technique. In this paper, we propose a new microfabrication method in which a point in three-dimensional volume of UV photopolymerizing resin is photopolymerized through two-photon absorption process. The microfabrication with two-photon absorption drastically improves the depth resolution due to a nonlinearlity between the power of the irradiation and that of the absorption[5].

Three-dimensional microfabrication with two-photon absorbed photopolymerization

Light-initiated polymerization processes are currently an important tool in various industrial fields. The advancement of technology has resulted in the use of photopolymerization in various biomedical applications, such as the production of 3D hydrogel structures, the encapsulation of cells, and in drug delivery systems. The use of photopolymerization processes requires an appropriate initiating system that, in biomedical applications, must meet additional criteria such as high water solubility, non-toxicity to cells, and compatibility with visible low-power light sources. This article is a literature review on those compounds that act as photoinitiators of photopolymerization processes in biomedical applications. The division of initiators according to the method of photoinitiation was described and the related mechanisms were discussed. Examples from each group of photoinitiators are presented, and their benefits, limitations, and applications are outlined.

https://www.mdpi.com/2073-4360/12/5/1073/pdf

Water-Soluble Photoinitiators in Biomedical Applications.

Advances in biomaterials and the need for patient-specific bone scaffolds require modern manufacturing approaches in addition to a design strategy. Hybrid materials such as those with functionally graded properties are highly needed in tissue replacement and repair. However, their constituents, proportions, sizes, configurations and their connection to each other are a challenge to manufacturing. On the other hand, various bone defect sizes and sites require a cost-effective readily adaptive manufacturing technique to provide components (scaffolds) matching with the anatomical shape of the bone defect. Additive manufacturing or three-dimensional (3D) printing is capable of fabricating functional physical components with or without porosity by depositing the materials layer-by-layer using 3D computer models. Therefore, it facilitates the production of advanced bone scaffolds with the feasibility of making changes to the model. This review paper first discusses the development of a computer-aided-design (CAD) approach for the manufacture of bone scaffolds, from the anatomical data acquisition to the final model. It also provides information on the optimization of scaffold’s internal architecture, advanced materials, and process parameters to achieve the best biomimetic performance. Furthermore, the review paper describes the advantages and limitations of 3D printing technologies applied to the production of bone tissue scaffolds.

/pdf/challenges-on-optimization-of-3d-printed-bone-scaffolds-3n5wzq889a.pdf

Challenges on optimization of 3D-printed bone scaffolds

Acrylate nanoanchors of subdiffraction-limited diameter are written with optical stimulated emission depletion (STED) lithography. After incubation, 98% of all nanoanchors are loaded quickly with fluorescently labeled antibodies. Controlling the size of the nanoanchors allows for limiting the number of the antibodies. Direct stochastic optical reconstruction microscopy (dSTORM) imaging, statistical distribution of fluorescence, quantitative fluorescence readout, and single molecule blinking consistently prove that 80% of the nanoanchors with a 65 nm diameter are carrying only one antibody each, which are functional as confirmed with live erythrocytes.

Nano-anchors with single protein capacity produced with STED lithography.

VUV treatment combined with mechanical strain of stretchable polymer foils resulting in cell alignment

Polymer micro- and nanostructures with various geometries can be written onto a transparent substrate by the technique of two-photon polymerization by a Ti-sapphire femtosecond-laser, which is focused into a liquid acrylate based resin containing a photo-initiator. The microstructures can be employed either as three-dimensional tissue scaffold onto which adherent cells can be seeded or are used as topological substrates for wetting experiments. Due to confinement to the microstructures and/or mechanical interaction with the scaffold, skin derived cells can be stimulated to grow three-dimensionally and to produce calcium binding proteins. The periodic laser-written structures may have other potential applications in the field of bio-inspired microfluidic devices due to their good wettability and water sustainment.

Three-dimensional photonic structures on transparent substrates fabricated by two-photon polymerization for use as cell substrates and for wetting experiments

The main aim of this work was to stimulate bone-forming cells to produce three-dimensional networks of mineralized proteins such as those occurring in bones. This was achieved by a novel approach using a specific type of mesenchymal progenitor cells (i.e., primary fibroblast cells from human hair roots) seeded on to polymer scaffolds. We wrote polymer microstructures with one or more levels of quadratic pores on to a flexible substrate by means of two-photon polymerization using a Ti-sapphire femtosecond laser focused into a liquid acrylate-based resin containing a photoinitiator. Progenitor cells, differentiated into an osteogenic lineage by the use of medium supplemented with biochemical stimuli, can be seeded on to the hydrophilic three-dimensional scaffolds. Due to confinement to the microstructures and/or mechanical interaction with the scaffold, the cells are stimulated to produce high amounts of calcium-binding proteins, such as collagen type I, and show an increased activation of the actin cytoskeleton. The best results were obtained for quadratic pore sizes of 35 µm: the pore volumes become almost filled with both cells in close contact with the walls of the structure and with extracellular matrix material produced by the cells. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 891-899, 2017.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jbm.a.35959

Bone‐forming cells with pronounced spread into the third dimension in polymer scaffolds fabricated by two‐photon polymerization

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Nano-anchors with single protein capacity produced with STED lithography.

VUV treatment combined with mechanical strain of stretchable polymer foils resulting in cell alignment

Three-dimensional photonic structures on transparent substrates fabricated by two-photon polymerization for use as cell substrates and for wetting experiments

Bone‐forming cells with pronounced spread into the third dimension in polymer scaffolds fabricated by two‐photon polymerization