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Regenerative medicine is a rapidly developing field with far-reaching potential. To sustain progress in this field, new advanced structures are needed. These include scaffolds for cell growth. Direct laser writing (DLW) based on femtosecond laser multi-photon polymerization (MPP) was shown to be an attractive technology for such structure fabrication as it combines vast selection of materials and the possibility to choose feature size in scaffold to be smaller, bigger, or around the same size as a cell. At the same, there are issues related to throughput which limit the widespread implementation of MPP for scaffold manufacturing. It is further compounded by some material limitations making it difficult to print mechanically flexible scaffolds for soft tissue regeneration. In this paper, we propose printing mechanically flexible scaffolds out of mechanically rigid material SZ2080 by employing chainmail architecture. We explore capabilities to optimize the printing procedure of this kind of scaffold, achieving printing times of less than 10 min for a 1 × 1 mm scaffold while maintaining micro-level precision. The superb biocompatibility of such scaffolds is shown both qualitatively and quantitatively and is proven to be independent of the used photoinitiator. Finally, manipulations of scaffolds with cells are performed with no adverse impact on the cell viability or proliferation after such procedures. Overall, this work proposes a methodology for rapid printing of shape-shifting scaffolds which could be used in regenerative medicine both for cell cultivation and potential direct implantation into soft tissue. [Display omitted] • Mechanically flexible micro-chainmail were 3D printed out of hard material SZ2080. • Smart scanning technique that allowed to increase throughput tenfold was created. • Cells were shown to proliferate up to 30% better on scaffolds than on control samples. • After mechanical manipulation cells showed high viability/proliferation on chainmails. [ABSTRACT FROM AUTHOR]

An approach employing ultrafast laser hybrid subtractive-additive microfabrication, which combines ablation, three-dimensional nanolithography, and welding, is proposed for the realization of a lab-on-chip (LOC) device. A single amplified Yb:KGW femtosecond (fs)-pulsed laser source is shown to be suitable for fabricating microgrooves in glass slabs, polymerization of fine-meshes microfilter out of hybrid organic–inorganic photopolymer SZ2080 inside them, and, finally, sealing the whole chip with cover glass into a single monolithic piece. The created microfluidic device proved its particle sorting function by separating 1- and 10-μm polystyrene spheres in an aqueous mixture. All together, this proves that laser microfabrication based on a single amplified fs laser source is a flexible and versatile approach for the hybrid subtractive-additive manufacturing of functional mesoscale multimaterial LOC devices. [ABSTRACT FROM AUTHOR]

We propose a laser fabrication approach for single monolith structure by varying beam focusing lenses (NA1 = 1.4 and NA2 = 0.45). With this, we show great improvement of the manufacturing throughput while keeping the desired spatial resolution and feature definition. To quantitatively evaluate its efficiency, we theoretically calculate and experimentally measure the polymerized volume using different focusing conditions and show that the augmentation can reach more than sevenfold. Based on this, sample structures of hybrid organic-inorganic SZ2080 and hydrogel polyethylene (glycol) diacrylate photopolymers were successfully manufactured. These three-dimensional structures included prototype scaffolds for cell growth and microfluidic components. Their quality was assessed and possible difficulties as well as limitations that arose were discussed. The new structures were compared to alternative direct laser writing throughput increasing techniques. Finally, we discussed potential applications in manufacturing various elements for regenerative medicine and microfluidics. [ABSTRACT FROM AUTHOR]

Three-dimensional cancer cell cultures have been a valuable research model for developing new drug targets in the preclinical stage. However, there are still limitations to these in vitro models. Scaffold-based systems offer a promising approach to overcoming these challenges in cancer research. In this study, we show that two-photon polymerization (TPP)-assisted printing of scaffolds enhances 3D tumor cell culture formation without additional modifications. TPP is a perfect fit for this task, as it is an advanced 3D-printing technique combining a μm-level resolution with complete freedom in the design of the final structure. Additionally, it can use a wide array of materials, including biocompatible ones. We exploit these capabilities to fabricate scaffolds from two different biocompatible materials—PEGDA and OrmoClear. Cubic spheroid scaffolds with a more complex architecture were produced and tested. The biological evaluation showed that the human ovarian cancer cell lines SKOV3 and A2780 formed 3D cultures on printed scaffolds without a preference for the material. The gene expression evaluation showed that the A2780 cell line exhibited substantial changes in CDH1, CDH2, TWIST, COL1A1, and SMAD3 gene expression, while the SKOV3 cell line had slight changes in said gene expression. Our findings show how the scaffold architecture design impacts tumor cell culture 3D spheroid formation, especially for the A2780 cancer cell line. [ABSTRACT FROM AUTHOR]

Organ-on-a-chip devices are gaining popularity in medical research due to the possibility of performing extremely complex living-body-resembling research in vitro. For this reason, there is a substantial drive in developing technologies capable of producing such structures in a simple and, at the same time, flexible manner. One of the primary challenges in producing organ-on-chip devices from a manufacturing standpoint is the prevalence of layer-by-layer bonding techniques, which result in limitations relating to the applicable materials and geometries and limited repeatability. In this work, we present an improved approach, using three dimensional (3D) laser lithography for the direct integration of a functional part—the membrane—into a closed-channel system. We show that it allows the freely choice of the geometry of the membrane and its integration into a complete organ-on-a-chip system. Considerations relating to sample preparation, the writing process, and the final preparation for operation are given. Overall, we consider that the broader application of 3D laser lithography in organ-on-a-chip fabrication is the next logical step in this field's evolution. [ABSTRACT FROM AUTHOR]

Recent advances in material engineering have shown that renewable raw materials, such as plant oils or glycerol, can be applied for synthesis of polymers due to ready availability, inherent biodegradability, limited toxicity, and existence of modifiable functional groups and eventually resulting to a potentially lower cost. After additional chemical modifications (epoxidation, acrylation, double bonds metathesis, etc.), they can be applied in such high-tech areas as stereolithography, which allows fabrication of three-dimensional (3-D) objects. "Autodesk's" 3-D optical printer "Ember" using 405-nm light was implemented for dynamic projection lithography. It enabled straightforward spatio-selective photopolymerization on demand, which allows development of various photosensitive materials. The bio-based resins' photosensitivity was compared to standard "Autodesk" "PR48" and "Formlabs" "Clear" materials. It turned out that the bioresins need a higher energy dose to be cured (a least 16 J · cm-2 for a single layer varying from 100 to 130 µm). Despite this, submillimeter range 2.5-D structural features were formed, and their morphology was assessed by optical profilometer and scanning electron microscope. It was revealed that a higher exposition dose (up to 26 J · cm-2) results in a linear increase in the formed structures height, proving controllability of the undergoing process. Overall, the provided results show that naturally derived resins are suitable candidates for tabletop gray-tone lithography. [ABSTRACT FROM AUTHOR]

Selective laser etching (SLE) is a technique that allows the fabrication of arbitrarily shaped glass micro-objects. In this work, we show how the capabilities of this technology can be improved in terms of selectivity and etch rate by applying an etchant solution based on a Potassium Hydroxide, water, and isopropanol mixture. By varying the concentrations of these constituents, the wetting properties, as well as the chemical reaction of fused silica etching, can be changed, allowing us to achieve etching rates in modified fused silica up to 820 μm/h and selectivity up to ∼3000. This is used to produce a high aspect ratio (up to 1:1000), straight and spiral microfluidic channels which are embedded inside a volume of glass. Complex 3D glass micro-structures are also demonstrated. [ABSTRACT FROM AUTHOR]

The femtosecond (fs) laser is a well-established tool in material processing. Due to highly nonlinear light–matter interaction in a time frame shorter than heat dissipation from the laser affected zone, fs pulses enable extremely precise "cold processing". Both additive and subtractive structuring can be realized. Here we demonstrate how medical device fabrication can benefit from 3D additive-subtractive fs processing. The produced functional element is a microfluidic macromolecule separator based on integrated nanofilters. The channel system is produced using direct laser ablation and is ∼ cm in overall size with channels with 150-250 μ m cross section. The filters are integrated by 3D laser lithography. Pore sizes—250–1500 nm. Furthermore, various channel sealing solutions are considered, discussing their advantages and disadvantages. A selective multi-photon polymerization-based solution is chosen for channel sealing, finishing the microfluidic system. The overall throughput of the process is considered, showing that it is near-capable for mass production. We demonstrated that the capability of freely choosing between additive and subtractive structuring in one highly automated workstation simplifies the design and fabrication process. [ABSTRACT FROM AUTHOR]