Skin is the tissue dedicated to the protection of the inner part of the body. It acts as a sensor for most of our sensations, such as the sense of temperature and pressure. This tissue can often undergo injuries, infections, or stresses, constantly being exposed to external agents and events [1].

Skin disorders and damages are emerging as one of the most troubling and challenging conditions for the healthcare systems in terms of rising cases, management, and correlated costs [2,3,4]. Acute and chronic wounds, diabetic ulcers, burns, psoriasis, and atopic dermatitis (AD) are the most diffused and alarming impairs of the skin tissue involving thousands of millions of people worldwide [5,6,7]. These conditions are connected with either genetic factors, metabolic alterations, environmental factors and lifestyle, injuries, or a combination thereof. Antimicrobial resistance is also playing a significant role in the development of secondary effects and in enhancing these alterations, aggravating the patients’ prognosis [8]. The concurrent abuse of soaps and hand disinfectants due to the COVID-19 pandemic might even support the onset of new disorders tightly connected with skin health and homeostasis modification. Indeed, the use of aggressive soaps and disinfectants can alter the equilibrium of the microbial environment, usually present in healthy skin, and modify the local pH, becoming a source of stress and irritation for the skin [9,10].

All these alterations are characterized mainly by the presence of a high concentration of free radicals and/or abnormal inflammatory response. For instance, after a burn event, a massive amount of reactive oxygen species (ROS) is generated. They can propagate the damage not only at the local but also to a systemic level, affecting other tissues and organs. This event recalls inflammatory cells, which can consequently contribute to increasing the ROS local and systemic generation. [11]. A similar scenario can be found in chronic diabetic ulcers, where the wound healing process is profoundly modified by the persistent hyper-glycemia condition. Here, a chronic inflammatory response is present, and an enormous quantity of inflammatory mediators and ROS are constantly released [12]. However, it is difficult to find a single molecular target due to the overlap of several altered molecular and metabolic pathways. Likewise, in dermatitis and psoriasis, the physiological alterations of the skin are attributed to upregulation of the release of pro-inflammatory mediators, such as chemokines and cytokines, requiring the use of anti-inflammatories such as corticosteroids [13,14]. In this scenario, natural compounds are gaining attention in the scientific and industrial communities due to their biocompatibility, anti-oxidant, anti-inflammatory, and antimicrobial properties [15,16,17,18]. Among these compounds, hydroxycinnamic acids and their derivatives have been explored in several fields such as food packing [19], cosmetics [20], pharmaceuticals [21], and nutraceuticals [22].

Biomedical nanotechnologies can offer great help in the improvement of phenolic stability, duration, bioavailability, and delivery at the site of action, to allow efficient exploitation of the compound’s therapeutic properties [23,24]. Currently, eligible biomaterials for this kind of application require several characteristics and should be selected case by case, depending on the different physio-pathological conditions that each skin injury or disorder presents.

Other reviews have already faced the importance of the hydroxycinnamic acids and derivatives for other specific applications such as cosmetics [20], their pharmacodynamics [25], pharmacokinetics [26], and toxicity [27].

This class of compounds is synthetized via the shikimate pathway, a metabolic route used chiefly by plants but also fungi and algae. These molecules are involved in several functions inside the cells, which will be discussed in this section. In this review, we will focus our attention on cinnamic acid (CinAc), ferulic acid (FA), p-coumaric acid (PCA), caffeic acid (CA), vanillic acid (VA), syringic acid (SA), rosmarinic acid (RA), and chlorogenic acid (CGA). The chemical structures of these molecules are shown in Figure 1.