Breath figures in tissue engineering and drug delivery: State-of-the-art and future perspectives.

The breath figure (BF) method is an easy, low-cost method to prepare films with a highly organized honeycomb-like porous surface. The particular surface topography and porous nature of these materials makes them valuable substrates for studying the complex effects of topography on cell fate, and to produce biomimetic materials with high performance in tissue engineering. Numerous researchers over the last two decades have studied the effects of the honeycomb topography on a variety of primary and immortalized cell lines, and drew important conclusions that can be translated to the construction of optimal biomaterials for cell culture. The literature also encouragingly shows the potential of honeycomb films to induce differentiation of stem cells down a specific lineage without the need for biochemical stimuli. Here, we review the main studies where BF honeycomb films are used as substrates for tissue engineering applications. Furthermore, we highlight the numerous advantages of the porous nature of the films, such as the enhanced, spatially controlled adsorption of proteins, the topographical cues influencing cellular behavior, and the enhanced permeability which is essential both in vitro and in vivo. Finally, this review highlights the elegant use of honeycomb films as drug-eluting biomaterials or as reservoirs for distinct drug delivery systems. STATEMENT OF SIGNIFICANCE: Combining biocompatible surfaces and 3D nano/microscale topographies, such as pores or grooves, is an effective strategy for manufacturing tissue engineering scaffolds. The breath figure (BF) method is an easy technique to prepare cell culture substrates with an organized, honeycomb-like porous surface. These surface features make these scaffolds valuable for studying how the cells interact with the biomaterials. Their unique surface topography can also resemble the natural environment of the tissues in the human body. For that reason, numerous studies, using different cell types, have shown that honeycomb films can constitute high performance substrates for cell culture. Here, we review those studies, we highlight the advantages of honeycomb films in tissue engineering and we discuss their potential as unique drug-eluting systems.