Microstructures and nanostructures can be used to reduce the adhesion of the cells on the auxiliary material. Therefore, the aim of our work was to fabricate laser-induced hierarchical microstructures and nanostructures by femtosecond laser-treatment (wavelength 1040 nm, pulse length 350 fs, repetition rates in the kHz range) to reduce the cell adhesion. Additionally, surface chemistry modification by optimized electrochemical anodization was used to further reduce the cell adhesion. For testing, flat plates and bone screws made of Ti-6Al-4V were used. Bone-forming cells (human osteoblasts from the cell line SAOS-2) were grown on the bone implants and additional test samples for two to three weeks. After the growth period, the cells were characterized by scanning electron microscopy (SEM). While earlier experiments with fibroblasts had shown that femtosecond laser-processing followed by electrochemical anodization had a significant impact on cell adhesion reduction, for osteoblasts the same conditions resulted in an activation of the cells with increased production of extracellular matrix material. Significant reduction of cell adhesion for osteoblasts was only obtained at pre-anodized surfaces. It could be demonstrated that this functionalization by means of femtosecond laser-processing can result in bone screws that hinder the adhesion of osteoblasts.

Laser structuring enables modification of sample topography, surface chemistry, and/or physical properties of materials. Examples of these processes are ripple, nap or wall formation, surface oxidation, induction of polymerization reactions, or changes in crystallinity or contact angle. These – most of the time – interrelated modifications are exploited widely for biomedical applications. They range from cell-repellent surfaces for easy-to-replace cardiac pacemakers, control of cell proliferation required in regenerative medicine, to increased cell adhesion for cell arrays. Furthermore, ns-laser-induced nanoripples were used for formation of gold nanowires for future surface plasmon resonance sensors directly integrated into biotechnological devices. Additive nano- and microscale manufacturing by two-photon polymerization allows for considerable progress in cell scaffold formation, paving the path for in vitro–grown organs, bones, and cartilages. The very same fs-laser-based technique was also used for biomimetic microneedles with enhanced liquid spreading on their surface. Microneedles are promising candidates for low-cost, high-throughput drug delivery and vaccination applicable even by nonmedically trained personnel. Microfluidic systems fabricated by fs-lasers have enabled progress in 3D microscopy of single cells and in studies on thrombocyte activation with the help of nanoanchors. Explicating the abovementioned and further biomedical applications, the authors put special focus on the achieved limits pointing out what scientists have accomplished so far in their pursuit of extreme scales.

The adhesion and alignment of osteoblasts and fibroblasts on titanium alloy (Ti-6Al-4V) surfaces can be adjusted over a wide range by femtosecond laser treatment and anodization. The great differences in cell behavior between different experimental conditions raised further questions about the role of cell migration, which will be addressed in this study. For that, Ti-6Al-4V surfaces were laser-structured to obtain a surface covered with ripples, i.e., laser-induced periodic surface structures (LIPSS), or micro-cones superimposed with ripples. Then, cells were seeded either directly onto the non-structured or laser-structured areas on the titanium alloy samples or beside such samples where they can reach the surface by cell migration. After two weeks in culture, the cell coverage of the samples was evaluated by scanning electron microscopy (SEM). The results showed that cells directly seeded onto the non-structured or laser-structured areas covered the surface nearly completely and eventually aligned along the ripple direction for the laser-structured areas. In contrast, for cell-seeding beside the samples, the laser-structured areas remain nearly cell-free while the non-structured areas were covered with cells in a similar non-oriented manner as for direct cell-seeding. These results on reduced osteoblast migration due to laser structuring are in line with the findings in animal experiments. There, the new bone formation of laser-processed samples was 26.1% ± 16.9% lower in comparison to untreated samples of the same type, which can be explained by hindered cell migration on the laser-processed areas of the screws.