The design of advanced functional devices often requires the use of intrinsically curved geometries that belong to the realm of non‐Euclidean geometry and remain a challenge for traditional engineering approaches. Here, it is shown how the simple deflection of thick meta‐plates based on hexagonal cellular mesostructures can be used to achieve a wide range of intrinsic (i.e., Gaussian) curvatures, including dome‐like and saddle‐like shapes. Depending on the unit cell structure, non‐auxetic (i.e., positive Poisson ratio) or auxetic (i.e., negative Poisson ratio) plates can be obtained, leading to a negative or positive value of the Gaussian curvature upon bending, respectively. It is found that bending such meta‐plates along their longitudinal direction induces a curvature along their transverse direction. Experimentally and numerically, it is shown how the amplitude of this induced curvature is related to the longitudinal bending and the geometry of the meta‐plate. The approach proposed here constitutes a general route for the rational design of advanced functional devices with intrinsically curved geometries. To demonstrate the merits of this approach, a scaling relationship is presented, and its validity is demonstrated by applying it to 3D‐printed microscale meta‐plates. Several applications for adaptive optical devices with adjustable focal length and soft wearable robotics are presented.

The surface topography of implantable devices is of crucial importance for guiding the cascade of events that starts from the initial contact of the cells with the surface and continues until the complete integration of the device in its immediate environment. There is, however, limited quantitative information available regarding the relationships between the different stages of such cascade(s) and how the design of surface topography influences them. We, therefore, used direct laser writing to 3D-print submicron pillars with precisely controlled dimensions and spatial arrangements to perform a systematic study of such relationships. Using single-cell force spectroscopy, we measured the adhesion force and the work of adhesion of the preosteoblast cells residing on the different types of surfaces. Not only the adhesion parameters (after 2–60 s) but also the formation of focal adhesions was strongly dependent on the geometry and arrangement of the pillars: sufficiently tall and dense pillars enhanced both adhesion parameters and the formation of focal adhesions. Our morphological study of the cells (after 24 h) showed that those enhancements were associated with a specific way of cell settlement onto the surface (i.e., “top state”). The cells interacting with tall and dense pillars were also characterized by numerous thick actin stress fibers in the perinuclear region and possibly high internal stresses. Furthermore, living cells with highly organized cytoskeletal networks exhibited greater values of the elastic modulus. The early responses of the cells predicted their late response including matrix mineralization: tall and dense submicron pillars significantly upregulated the expression of osteopontin after 21 days of culture under both osteogenic and nonosteogenic conditions. Our findings paint a detailed picture of at least one possible cascade of events that starts from initial cell adhesion and continues to subsequent cellular functions and eventual matrix mineralization. These observations could inform the future developments of instructive surfaces for medical devices based on physical surface cues and early markers.

The surface topography of engineered extracellular matrices is one of the most important physical cues regulating the phenotypic polarization of macrophages. However, not much is known about the ways through which submicron (i.e., 100–1000 nm) topographies modulate the polarization of macrophages. In the context of bone tissue regeneration, it is well established that this range of topographies stimulates the osteogenic differentiation of stem cells. Since the immune response affects the bone tissue regeneration process, the immunomodulatory consequences of submicron patterns should be studied prior to their clinical application. Here, we 3D printed submicron pillars (using two-photon polymerization technique) with different heights and interspacings to perform the first ever systematic study of such effects. Among the studied patterns, the highest degree of elongation was observed for the cells cultured on those with the tallest and densest pillars. After 3 days of culture with inflammatory stimuli (LPS/IFN-γ), sparsely decorated surfaces inhibited the expression of the pro-inflammatory cellular marker CCR7 as compared to day 1 and to the other patterns. Furthermore, sufficiently tall pillars polarized the M1 macrophages towards a pro-healing (M2) phenotype, as suggested by the expression of CD206 within the first 3 days. As some of the studied patterns are known to be osteogenic, the osteoimmunomodulatory capacity of the patterns should be further studied to optimize their bone tissue regeneration performance.

Fabricating large areas of geometrically complex and precisely controlled topographies is required for the studies of cell behavior on patterned surfaces. Direct laser writing (DLW) is an advanced 3D-fabrication technique, which facilitates the manufacturing of structures within various scales (from a few hundred nanometers to millimeters). However, this method requires improvements in the accuracy and reproducibility of the submicron and nanoscale features that are printed over a large area. Here, we present a scheme to both improve the uniformity of the printed submicron patterns and decrease the printing time. The effects of various processing parameters (e.g., laser power and writing field) on the dimensions and uniformity of submicron pillars as well as on their Young’s modulus and surface wettability were assessed. Decreasing the writing field to 33 × 33 µm2 significantly improved the uniformity of submicron pillars that were printed over an area of 4 mm2 in a single-step process. Preosteoblast cells (MC3T3-E1) were used to assess the cytocompatibility of the used material (IP-L780 resin) with a focus on cell morphology, cell proliferation, cytoskeletal organization, and the elastic modulus of the cells. The cells cultured for two days on the submicron pillars showed a polarized shape and a higher Young’s modulus of the area corresponding to the nucleus relative to those cultured on flat surfaces. Taken together, the results of the current study clearly show that the submicron patterns created using DLW are both cytocompatible and could modulate the morphology and mechanical properties of cells. This work paves the way for direct printing of submicron features with controlled Young’s moduli over large areas in a single-step process, which is necessary for systematically studying how such patterns modulate cellular functions.

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) micro-scaffolds and submicron/nano-scale 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 to fabricate a microfluidic platform embedded with a large area (mm range) of reproducible submicron pillar-based topographies. Using the two photons 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 multi-scale fabrication capabilities of this approach, submicron pillars of various heights were integrated onto the surfaces of a 3D micro-scaffold 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 device. This proof-of-principle study, therefore, marks a significant step forward in manufacturing submicron structure-on-a-chip models for bone regeneration studies.

The treatment of articular cartilage defects remains a significant clinical challenge. This is partially due to current tissue engineering strategies failing to recapitulate native organization. Articular cartilage is a graded tissue with three layers exhibiting different cell densities: the superficial zone having the highest density and the deep zone having the lowest density. However, the introduction of cell gradients for cartilage tissue engineering, which could promote a more biomimetic environment, has not been widely explored. Here, we aimed to bioprint a scaffold with different zonal cell densities to mimic the organization of articular cartilage. The scaffold was bioprinted using an alginate-based bioink containing human articular chondrocytes. The scaffold design included three cell densities, one per zone: 20 × 10⁶ (superficial), 10 × 10⁶ (middle), and 5 × 10⁶ (deep) cells/mL. The scaffold was cultured in a chondrogenic medium for 25 days and analyzed by live/dead assay and histology. The live/dead analysis showed the ability to generate a zonal cell density with high viability. Histological analysis revealed a smooth transition between the zones in terms of cell distribution and a higher sulphated glycosaminoglycan deposition in the highest cell density zone. These findings pave the way toward bioprinting complex zonal cartilage scaffolds as single units, thereby advancing the translation of cartilage tissue engineering into clinical practice.