The topographic features of an implant, which mechanically regulate cell behaviors and functions, are critical for the clinical success in tissue regeneration. How cells sense and respond to the topographical cues, e.g., interfacial roughness, is yet to be fully understood and even debatable. Here, the mechanotransduction and fate determination of human mesenchymal stem cells (MSCs) on surface roughness gradients are systematically studied. The broad range of topographical scales and high‐throughput imaging is achieved based on a catecholic polyglycerol coating fabricated by a one‐step‐tilted dip‐coating approach. It is revealed that the adhesion of MSCs is biphasically regulated by interfacial roughness. The cell mechanotransduction is investigated from focal adhesion to transcriptional activity, which explains that cellular response to interfacial roughness undergoes a direct force‐dependent mechanism. Moreover, the optimized roughness for promoting cell fate specification is explored.

Material surface topographic features have been shown to be crucial for tissue regeneration and surface treatment of implanted devices. Many biomaterials were investigated with respect to the response of cells on surface roughness. However, some conclusions even conflicted with each other due to the unclear interplay of surface topographic features and substrate elastic features as well as the lack of mechanistic studies. Herein, wide-scale surface roughness gradient hydrogels, integrating the surface roughness from nanoscale to microscale with controllable stiffness, were developed via soft lithography with precise surface morphology. Based on this promising platform, we systematically studied the mechanosensitive response of human mesenchymal stem cells (MSCs) to a broad range of roughnesses (200 nm to 1.2 μm for R q) and different substrate stiffnesses. We observed that MSCs responded to surface roughness in a stiffness-dependent manner by reorganizing the surface hierarchical structure. Surprisingly, the cellular mechanoresponse and osteogenesis were obviously enhanced on very soft hydrogels (3.8 kPa) with high surface roughness, which was comparable to or even better than that on smooth stiff substrates. These findings extend our understanding of the interactions between cells and biomaterials, highlighting an effective noninvasive approach to regulate stem cell fate via synergetic physical cues.

Although mussel‐inspired surface chemistry is one of the most utilized strategies for surface functionalization, its practical and/or industrial applications are rather limited, because dip coating can only treat small surface areas and is dependent on the coating vessel. Herein a mussel‐inspired, polymer‐based, multifunctional, and substrate‐independent spray coating strategy for surface modification under extremely mild conditions using mussel‐inspired polyglycerol is described. The postfunctionalization of the obtained surface via spray coating with silver nanoparticles results in a nanoparticle embedded coating with excellent, long‐term antibacterial properties. Furthermore, a simple method for preparing a superhydrophobic, highly water‐repellent coating by coformulation of the mussel‐inspired spray coating with hydrophobic nanoparticles is presented.

Facile approaches for the fabrication of substrate independent superamphiphobic surfaces that can repel both water and organic liquids have been limited. The design of such super-repellent surfaces is still a major challenge of surface chemistry and physics. Herein, we describe a simple and efficient dip-coating approach for the fabrication of highly hierarchical surface coatings with superamphiphobic properties for a broad range of materials based on a mussel-inspired dendritic polymer (MI-dPG). The MI-dPG coating process provides a precise roughness control, and the construction of highly hierarchical structures was achieved either directly by pH-controlled aggregation or in combination with nanoparticles (NP). Moreover, the fabrication of coatings with a thickness and roughness gradient was possible via simple adjustment of the depth of the coating solution. Subsequent postmodification of these highly hierarchical structures with fluorinated molecules yielded a surface with superamphiphobic properties that successfully prevented the wetting of liquids with a low surface tension down to about 30 mN/m. The generated superamphiphobic coatings exhibit impressive repellency to water, surfactant containing solutions, and biological liquids, such as human serum, and are flexible on soft substrates.

Cells reside in a dynamic microenvironment in which adhesive ligand availability, density, and diffusivity are key factors regulating cellular behavior. Here, the cellular response to integrin‐binding ligand dynamics by directly controlling ligand diffusivity via tunable ligand–surface interactions is investigated. Interestingly, cell spread on the surfaces with fast ligand diffusion is independent of myosin‐based force generation. Fast ligand diffusion enhances α5β1 but not αvβ3 integrin activation and initiates Rac and RhoA but not ROCK signaling, resulting in lamellipodium‐based fast cell spreading. Meanwhile, on surfaces with immobile ligands, αvβ3 and α5β1 integrins synergistically initiate intracellular‐force‐based canonical mechanotransduction pathways to enhance cell adhesion and osteogenic differentiation of stem cells. These results indicate the presence of heretofore‐unrecognized pathways, distinct from canonical actomyosin‐driven mechanisms, that are capable of promoting cell adhesion.