Folding nanopatterned flat sheets into complex 3D structures enables the fabrication of meta-biomaterials that combine a rationally designed 3D architecture with nanoscale surface features. Self-folding is an attractive approach for realizing such materials. However, self-folded lattices are generally too compliant as there is an inherent competition between ease-of-folding requirements and final load-bearing characteristics. Inspired by sheet metal forming, an alternative route is proposed for the fabrication of origamilattices. This ‘automated-folding’ approach allows for the introduction of sharp folds into thick metal sheets, thereby enhancing their stiffness. The first time realization of automatically folded origami lattices with bone-mimicking mechanical properties is demonstrated. The proposed approach is highly scalable given that the unit cells making up the meta-biomaterial can be arbitrarily large in number and small in dimensions. To demonstrate the scalability and versatility of the proposed approach, it is fabricated origamilattices with > 100 unit cells, lattices with unit cells as small as 1.25 mm, and auxetic lattices. The nanopatterned the surface of the sheets prior to folding. Protected by a thin coating layer, these nanoscale features remained intact during the folding process. It is found that the nanopatterned folded specimens exhibits significantly increased mineralization as compared to their non-patterned counterparts.

We systematically reviewed the currently available evidence on how the design parameters of surface nanopatterns (e.g. height, diameter, and interspacing) relate to their bactericidal behavior. The systematic search of the literature resulted in 46 studies that satisfied the inclusion criteria of examining the bactericidal behavior of nanopatterns with known design parameters in absence of antibacterial agents. Twelve of the included studies also assessed the cytocompatibility of the nanopatterns. Natural and synthetic nanopatterns with a wide range of design parameters were reported in the included studies to exhibit bactericidal behavior. However, most design parameters were in the following ranges: heights of 100–1000 nm, diameters of 10–300 nm, and interspacings of <500 nm. The most commonly used type of nanopatterns were nanopillars, which could kill bacteria in the following range of design parameters: heights of 100–900 nm, diameters of 20–207 nm, and interspacings of 9–380 nm. The vast majority of the cytocompatibility studies (11 out of 12) showed no adverse effects of bactericidal nanopatterns with the only exception being nanopatterns with extremely high aspect ratios. The paper concludes with a discussion on the evidence available in the literature regarding the killing mechanisms of nanopatterns and the effects of other parameters including surface affinity of bacteria, cell size, and extracellular polymeric substance (EPS) on the killing efficiency. Statement of significance: The use of nanopatterns to kill bacteria without the need for antibiotics represents a rapidly growing area of research. However, the optimum design parameters to maximize the bactericidal behavior of such physical features need to be fully identified. The present manuscript provides a systematic review of the bactericidal nanopatterned surfaces. Identifying the effective range of dimensions in terms of height, diameter, and interspacings, as well as covering their impact on mammalian cells, has enabled a comprehensive discussion including the bactericidal mechanisms and the factors controlling the bactericidal efficiency. Overall, this review helps the readers have a better understanding of the state-of-the-art in the design of bactericidal nanopatterns, serving as a design guideline and contributing to the design of future experimental studies.

Manufacturing high throughput in vitro models resembling the tissue microenvironment is highly demanded for studying bone regeneration. Tissues such as bone have complex multiscale architectures inside which cells reside. To this end, engineering a microfluidic platform incorporated with three-dimensional (3D) microscaffolds and submicron/nanoscale topographies can provide a promising model for 3D cell cultures. There are, however, certain challenges associated with this goal, such as the need to decorate large surfaces area with high-fidelity 3D submicron structures. Here, we succeeded in fabricating a microfluidic platform embedded with a large area (mm range) of reproducible submicron pillar-based topographies. Using the two-photon polymerization (2PP) as a 3D printing technique based on direct laser writing, uniform submicron patterns were created through optimization of the process parameters and writing strategy. To demonstrate the multiscale fabrication capabilities of this approach, submicron pillars of various heights were integrated onto the surfaces of a 3D microscaffold in a single-step 2PP process. The created submicron topography was also found to improve the hydrophilicity of the surface while being able to withstand flow rates of up to 8 mL/min. The material (IP-Dip resin) used for patterning did not have cytotoxic effects against human mesenchymal stromal cells after 3 days of dynamic culture in the microfluidic device. This proof-of-principle study, therefore, marks a significant step forward in manufacturing submicron structure-on-a-chip models for bone regeneration studies.