potential in applications such as additive manufacturing, civil engineering, and biomedicine. [1][2][3][4][5][6] Among them, azobenzene-based materials, due to their unique photo-responsive features, have attracted great attention for the remote and flexible control of materials properties via light stimulation. [7,8] The light response is triggered by photoisomerization of the azobenzene units using UV or visible irradiation, [9] providing the basis for a variety of photonic applications such as energy storage, [10,11] holographic recording, [12][13][14] soft robotics, [15,16] dynamic control of surface topology in liquid crystalline elastomers [17] and nonlinear optics [18,19] where, in particular, photoinduced reorientation allows for all-optical poling. [20] As one striking example, by controlling the impinging light configuration, the photoinduced processes in azobenzene-containing thin films invoke material mass migration that leads to the formation of topographic surface patterns, a prominent example being surface-relief grating (SRG) formation upon irradiation with a light interference pattern. [21][22][23][24] SRGs show great promise as diffractive photonic elements, [25,26] biosensing substrates, [27] or as nano-/microfabrication templates. [28][29][30] The micron-scale periodicity of SRGs renders them an excellent fit for biological systems, many of which are composed of cells that are extremely sensitive to mechanical and topographic features of the surrounding microenvironment. [31,32] Hence, there is a growing interest in the use of azobenzene-based materials as smart bio-interfaces for cell culture. [33][34][35] The native extracellular matrix (ECM) of soft tissue is composed of entangled fibrous proteins, [36,37] as reproduced also in many synthetic ECM products. [38] Furthermore, ECM is continuously remodeled by the cells in physiological and pathological conditions. [39] Sinusoidal SRGs and embossed pillars in azobenzene thin films have been used for mimicking the ECM texture and controlling cellular directional migration in single and multiple cells, [40][41][42] directing axonal extension, [43,44] and determining stem cell fate. [45] The most exciting characteristic provided by azobenzenebased systems lies in the reversibility of the photoinduced processes. It is well known that SRGs recorded in thin films can be erased by heating the sample above the glass transition temperature (T g ). [46,47] SRGs can be also efficiently erased and re-inscribed optically by using single-beam irradiation [24,48,49] or Azobenzene-based light-responsive thin films are emerging as appealing candidates for smart cell-culture substrates. Their attraction lies in the fact that they can be reversibly photo-patterned, providing a route for dynamically mimicking the remodeling of the extracellular matrix. However, since the cells need to be cultured in aqueous environment, a key parameter in the layout of any biological application is the stability of the surface underwater. In this work, the authors perform a detail...