**1. Introduction**

The design of biomimetic biomaterials as scaffolds for cell culture is a powerful tool for studying and understanding fundamental cell behavior, specific tissue environment, degradation, and reasons for tissue damage [1]. Scaffolding structures should mimic not only biological properties of extracellular matrix (ECM), but also morphological and topographical features [2–4]. The ECM directs and modulates cell behavior, is composed of fibrous proteins (mainly collagens and elastin), glycosaminoglycans (GAGs), proteoglycans, and glycoproteins [5,6].

In order to emulate the natural structure of the ECM, different technologies have been developed. Current techniques for generating topographical features on polymeric scaffolds for cell culture, especially those with nano-scale resolution, are typically complex and expensive. Thus, a simple

and tunable fabrication method for the production of patterned biomimetic scaffold is still pending. By using electrospinning technology, it is possible to obtain micro- and/or nano-fibrous mats that mimic ECM [7,8]. The optimization of different processing parameters and the use of post-processing treatments allow handling dimensions, porosity, morphology, and the spatial arrangement of nanofibers. A huge variety of natural and/or synthetic polymeric solutions has been electrospun. Composition and processing techniques determine the scaffold architecture, mechanical performance, degradation rate, and cell-material interactions. Aligned and randomly oriented electrospun mats have been also developed to study how morphology affects cell behavior. Gao et al. studied the influence of aligned and randomly oriented fibrous gelatin/PLLA scaffolds to guide the growth of corneal stroma cells [9]. The aligned scaffold not only increased cell viability more significantly than that in a randomly oriented scaffold, but it also provided an external stimulus for the orderly arrangement of cells. Similar results were observed by Shalumon et al., who prepared aligned and randomly PLLA/gelatin nanofibrous scaffolds [10]. In these structures, an increase in viability and proliferation of human umbilical vein endothelial cells (HUVECs) and smooth muscle cells (SMCs) was observed.

On the other hand, substrates with various micro- and nano-features such as lines, wells, and holes among others have been explored to introduce significant effects on cell behavior [11]. Most of these reports relate the topographical features with cell orientation, migration, morphology, proliferation, cell gene expression, and differentiation [12–14].

The main goal of this work is to design gelatin-based scaffolds with micro and nano-topographical and morphological features, achieving a high resolution, and performance with low cost. In addition, gelatin, a biocompatible and biofunctional polymer, and benign solvents (Class 3 according to ICH guidelines) [15] are used for scaffold fabrication. Gelatin is an inexpensive biomacromolecule obtained from denatured collagen, and presents integrin cell-binding motifs, such as RGD and matrix metalloproteinases (MMP) degradable sites [16,17]. Compared to native collagen, gelatin has lower antigenicity and less batch-to-batch variation due to the denaturation process, in which tertiary protein structures are removed. Functionalization of amine-containing groups of gelatin with methacrylate groups was used to provide a photopolymerizable biomaterial named GelMA that has been widely investigated for cell-based studies and tissue engineering applications [18–22]. Crosslinking of the methacrylic side groups results in hydrogels with stiffness and density that can be controlled by varying the polymer dry mass, degree of functionalization, photo-initiator concentration, ultraviolet (UV) intensity, and exposure time. In this work, electrospinning and photolithography techniques were used to design 3D scaffolds with novel topographical features in micro- and nanoscale, while UV exposition time was varied. Moreover, the use of micropatterned molds with different sizes as collectors in the electrospinning process is proposed to produce electrospun fibrous mats.
