# Micro-Structured Patches for Dermal Regeneration Obtained via Electrophoretic Replica Deposition
## 1 Introduction  
The wound management of severe skin damage or loss is a clinical procedure required by a significant number of people who suffer from chronic diseases or have been involved in traumatic events [1]. Cutaneous wound regeneration remains a critical procedure for the treatment of those patients in which injuries compromising the integrity and the protective functions of skin would result in physiologic imbalance, relevant disability, or even death [2]. The healing of a skin wound is a complex phenomenon thatincludes a wide range of molecular, cellular, physiological, and biological processes: a deep understanding of the intricate cascade of events taking place during skin repair [3] offers fundamental guidelines for the design of wound dressings. Many skin substitutes, and a relevant number of solutions, have been developed so far to target wound healing processes by creating a suitable local micro-environment at the site of implant [4]. The ideal goal of a skin substitute is to rapidly produce a construct that provides the complete regeneration of the functional tissue by fulfilling its common functions: barrier formation, defense against UV irradiation, thermoregulation, mechanical, and aesthetic functions [1]. A variety of cutaneous wounds is reported, each one resulting in its own distinctive healing approach: different devices have been developed to address specific clinical needs [5], ranging from passive solutions to tissue grafts. The former solutions support a large number of current medical procedures and are based on simple devices such as gauzes and bandages, whose primary function is to control the local microenvironment by protecting the wound from pathogenic infections. More sophisticated strategies are based on skin grafts: even if they represent the gold standard in large acute and chronic wounds [6], autograft and allograft availability can be scarce and more generally hold several limitations [1]. The use of dermal substitutes represents an effective alternative in improving the quality of wound healing [7] when compared to passive solutions. More advanced wound dressings, further promoting tissue healing via the delivery of biologically active agents or cells [8] from the dressing materials, have hence been proposed [6]. However, a significant degree of complexity is associated with these solutions, being based on fabrication processes with some limitations in scale-up, difficult management of both loading and controlled release of bioactive agents and cells, and significant costs [9]. Electrophoretic deposition (EPD) is a simple yet effective technology largely investigated for the biopolymer processing of a wide variety of coatings for biomedical applications [10], owing to its versatility in fine-tuning the properties of the processed biomaterials with a simple method of fabrication [11]. Such versatility can be further exploited using an innovative two-steps approach, electrophoretic replica deposition (EPrD) [12], in which deposited biopolymers are peeled from the working electrode by replicating the surface and morphology of the patterned substrate. EPrD has been successfully used to tailor both chemical composition and microstructure in several applications [12; 13; 14], showing its potential in manufacturing hierarchical supports for tissue regeneration, mainly made of chitosan. Chitosan (CS) presents unique properties in terms of availability, handling, antibacterial and anti-inflammatory properties [15]. Next generation chitosan wound dressing can enhance wound progression towards healing by facilitating wound re-epithelialization and reducing the patient's pain level [16]. Chitosan's property of binding with red blood cells allows it to rapidly clot blood, making it effective in the treatment of severe hemorrhage [17]. In addition, chitosan modulates the response of inflammatory cells, subsequently promoting granulation and tissue organization [18].