**1. Introduction**

Skin, the major portion of the integumentary system, is the human body's largest organ. It spans approximately 2 m<sup>2</sup> and is 0.075–0.15 mm thick in the average adult [1]. It acts as the first line of defense to shield the human body from ultraviolet radiation, infection by pathogens, and chemical irritants [2]. Furthermore, skin plays a key role in thermoregulation, immunological function, and maintaining body water balance.

Schade and Marchionini first introduced the term "acid mantle" to describe the slight acidification of the uppermost layer of human skin [3]. The acid mantle is characterized by a pH value of 4–6, as a result of amino acids, fatty acids, sebum secreted by the sebaceous gland, and lactate excreted from sweat. All of these compounds are acidic and when present together on the human skin, become a barrier that prevents bacterial colonization. Another critical skin barrier is the lipid barrier, the extracellular lipid matrix of the stratum corneum (SC) [4], which is composed of free fatty acids, cholesterol and ceramides and functions as a hydrophobic barrier for human skin [5]. A skin barrier schematic is provided in Figure 1.

**Figure 1.** The scheme of the skin barrier. Lipid barrier sits atop the acid mantle and displays a pH value of 4–6. Pathogens can be various bacteria. Slight acidic environment is a disadvantage for bacterial colonization.

Most human-pathogen bacteria are inhibited by the acidic milieu on the surface of normal human skin, but this shield is disturbed when skin is wounded. The tissue beneath skin has a physiological pH of 7.4 [6], which raises the overall pH value at the wound site and provides advantages for bacterial colonization. Bacterial contaminants in wounds, e.g., *Staphylococcus aureus*, interfere with the normal wound healing process.

There are four phases in normal wound healing [7,8]: hemostasis, inflammation, proliferation, and remodeling. During hemostasis the wound is filled with fibrin and coagulated blood. Clots are formed to stop bleeding and seal the wound site until tissues are repaired. During inflammation, histamine is produced by basophils and mast cells to increase capillary permeability, which allows leukocytes such as neutrophils to migrate to the infected wound site and remove dead cells and pathogens. However, a failure in eliminating pathogens or the remaining high pH environment can be primary reasons for chronic wound development. During proliferation, epithelial cells increase in number, granulation tissue forms, and angiogenesis occurs. Healthy granulation tissues should be pink in color and uneven in texture. The final phase, remodeling, may take years to complete. The wound matrix undergoes degradation by metalloproteinases and new extracellular matrix (ECM) is created during remodeling. Scar tissue can form due to degradation or ECM generation disruption. While the alkaline milieu activates protease, which facilitates the removal of damaged components, excessive amounts of protease eventually destroy newly constructed tissue [9]. Moreover, alkaline pH values are usually found in chronic wounds, and are associated with an increased risk of bacterial colonization [10].

pH value is a critical factor in the wound healing process and could offer important physiological condition information regarding skin status and infection. It assists physicians with clinically relevant diagnosis and patient wounds care. It can be used, for instance, to determine whether wounds are infected, becoming chronic, provide monitored, real-time wound status, and ultimately facilitate proper treatment in a more timely manner.

Recently, multiple innovative and elegant smart wound dressings combined with either pH sensors or drug control-released carriers have been extensively studied [11–15]. With these promising technologies, wound monitoring procedures can be visualized and designed for use in clinics and at home. The first step in clinically managing and in self-managing wounds is to understand wound status. Advances in and implementation of such technologies may alter the course of wound care and improve quality of life.

The role of pH value in evaluating skin and wound status will be systematically discussed in this review. We will emphasize its clinical application and highlight significant research that leverages pH to promote precise diagnoses leading to the development of impactful medical devices. We will also discuss pH-related di fferences in caring for adult skin versus neonatal skin, which is thin and requires more rigorous e fforts for e ffective care.
