Cristina Plamadeala

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.

People with injuries to the peripheral nervous system suffer from paralysis of the facial muscles, fingers and hands or toes and feet, often for the rest of their lives, due to its poor functional regeneration. Therefore, to improve patients’ quality of life, there is an urgent need for conduits that effectively support the healing of large defects in nerve pathways through specific guidance of nerve cells. This paper describes two specific methods for achieving directed growth of Schwann cells, a type of glial cells that can support the regeneration of the nerve pathway by guiding the neuronal axons in the direction of their alignment. One method uses aligned polyamide-6 (PA-6) nanofibers produced via electrospinning on a very fast rotating structured collector, which enables easy nanofiber detachment, without additional effort. The other method implies the exposure of a poly(ethylene terephthalate) (PET) foil to a KrF* laser beam, that renders a nanorippled surface topography. Schwann cell growth on these substrates was inspected after one week of cultivation by means of scanning electron microscopy (SEM). For both methods we show that Schwann cells grow in a certain direction, predetermined by nanofiber and nanoripple orientation. In contrast, cells cultivated on randomly oriented nanofibers or unstructured surfaces, show an omnidirectional growth behavior. These two methods can be used to produce nerve conduits for the treatment of injuries to the peripheral nervous system.

People with injuries to the peripheral nervous system, due to its poor functional regeneration, suffer from paralysis of the facial muscles, fingers and hands, or toes and feet, often for the rest of their lives. Therefore, to improve patients' quality of life, there is an urgent need for conduits that effectively support the healing of large defects in nerve pathways through specific guidance of nerve cells. This paper describes two specific methods for achieving directed growth of Schwann cells, a type of glial cells that can support the regeneration of the nerve pathway by guiding the neuronal axons in the direction of their alignment. One method implies the exposure of a poly(ethylene terephthalate) (PET) foil to a KrF* laser beam, that renders a nanorippled surface topography. The other method uses aligned polyamide-6 (PA-6) nanofibers produced via electrospinning on a very fast rotating structured collector, which enables easy nanofiber detachment, without additional effort. Schwann cells growth on these substrates was inspected after one week of cultivation by means of scanning electron microscope (SEM). For both methods we show that Schwann cells grow in a certain direction, predetermined by nanoripples and nanofibers orientation. In contrast, cells cultivated onto unstructured surfaces or randomly oriented nanofibers, show an omnidirectional growth behavior.

In this paper we present polymer surfaces inspired by the calamistrum of cribellate spiders. The calamistrum resembles a micro-comb with a finger-print-like nanorippled topography, which allows cribellate spiders to handle and process nanofibers, without sticking to them. Due to its morphology, the calamistrum has a reduced surface for contact with the nanofibers, which therefore reduces the adhesive forces. Three different types of structured surfaces were prepared: nanostructured surfaces (ripples), microstructured surfaces (lines), and a combination of micro- and nanostructured surfaces (lines superimposed with ripples). Polymer lines were created using UV mask lithography. Nanoripples, i.e., laser-induced periodic surface structures, were fabricated by exposure to a KrF* laser beam. Nanofibers were produced and deposited onto each sample by electrospinning. To quantify each samples’ adhesiveness, a peel-off test was used, and the results were plotted and compared against the control samples–a flat polymer film. Our results indicate that lines have a stronger influence on the adhesion reduction than the nanoripples: nanoripples reduce fiber adhesion by 7%, whereas the lines reduce it by 28%. The highest adhesion reduction of 33% is obtained for the polymer surfaces with a combination of both lines and nanoripples. Our results open new insights in the field of artificial nanofiber adhesion on micro- and nanopatterned surfaces, which are essential when designing tools for nanofiber handling.

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.

Biomimetics is the interdisciplinary scientific field focused on the study and imitation of biological systems, with the aim of solving complex technological problems. In this paper, we present a new bio-inspired design for microneedles (MNs) and MN arrays, intended for rapidly coating the MNs with drug/vaccine. The biomimetic approach consists in ornamenting the lateral sides of pyramidal MNs with structures inspired by the external scent efferent systems of some European true bugs, which facilitate a directional liquid transport. To realize these MNs, two-photon polymerization (TPP) technique was used. Liquid coating capabilities of structured and non-structured MNs were compared. Moreover, both in-vivo and ex-vivo skin tests were performed to prove that MNs pierce the skin. We show that the arrays of MNs can be accurately replicated using a micro-moulding technique. We believe this design will be beneficial for the process of drug/vaccine loading onto the needles’ surfaces, by making it more efficient and by reducing the drug/vaccine wastage during MN coating process.