# Hyaluronic Acid-Based Wound Dressing with Antimicrobial Properties for Wound Healing Application
## 1 Introduction  
Skin represents a primary defence barrier of our body, providing protection against a microorganism's infiltration and dehydration [1]. A wound is defined as an injury of living tissue that causes a disruption in the continuity of the epithelial lining of the skin or mucosa resulting from a generically external damage (i.e., physical or thermal, typically one in which the skin is cut or broken). Additionally, wounds can be classified as acute following a skin injury that occurs suddenly due to an accident or surgical injury with healing in 8-12 weeks, while chronic wounds occur when they fail to progress through normal stages of healing and cannot be repaired in an orderly and timely manner (e.g., pressure ulcer, leg ulcer, diabetic ulcer and burns). Wound healing is a normal biological process achieved through four precise and highly programmed phases involving haemostasis, inflammation, proliferation and remodelling [2]. During haemostasis, vascular constriction and platelet aggregation, degranulation, and fibrin formation (thrombus) occur. Subsequently, the inflammation event allows neutrophil and monocyte infiltration, the last one differentiating into macrophage. The proliferation phase consists of the re-epithelialization, with cell migration, followed by the angiogenesis and collagen synthesis with new extracellular matrix (ECM) formation. Finally, the remodelling foresees the collagen remodelling and, subsequently, the vascular maturation and regression [3]. Many factors exist that could interfere with one or more of these phases, delaying or even impairing the wound healing process. Among these, infection is seen as one of the most pervasive causes in woundhealing failure. If skin protection is compromised, bacteria can colonize the wound, possibly leading to a critical state of interference with the healing process, also called infection. The most common bacteria found in wound chronic infections, and therefore often taken into account to test antibacterial properties, are _S. aureus_, _P. aeruginosa_, _Enterococcus faecalis_ and others. The role of infection is then notoriously determined by its ability to delay wound healing by extending the duration of the inflammatory response [4] and worsening tissue damage. Some studies have also attested a role of such bacterial cultures in causing failure in skin re-epithelialisation [5]. It follows that an antimicrobial activity is an essential requirement for an appropriate wound dressing. Wound dressing may be defined as a sterile dressing applied to a wound or incision using an aseptic technique with or without medication. Such a dressing must possess certain characteristics in order to be highly effective. An optimal wound dressing has to control the moisture around the wound, possess great transmission of gases, eliminate extra exudates, protect the wound from infections and microorganisms, decrease surface necrosis of the wound, carry out mechanical protection, be easily changed and removed, be biocompatible, biodegradable, elastic and nontoxic, relive the wound pain and, eventually, be cost acceptable [6]. Different synthetic and natural polymers, such as poly(caprolactone) (PCL), poly(vinyl alcohol) (PVA), collagen (COL), chitosan (CS), alginate (ALG) and hyaluronic acid (HA), have been used for the production of different wound dressings [7]. Among natural polymers, HA is ubiquitous in connective, epithelial and neural tissue, and is a non-sulphated, linear polysaccharide consisting of alternate N-acetyl-D-glucosamine and D-glucuron acid linked by \(\beta\)(1\(\rightarrow\)3) and \(\beta\)(1\(\rightarrow\)4) glycoside bonds, belonging to the glycosaminoglycans (GAGs) family [8; 9; 10] (Figure 1). HA and its derivatives offer long-term safety and a proven ability to reduce bacterial adhesion and biofilm formation. HA is bacteriostatic but not bactericidal, and exhibits dose-dependent effects on different microorganisms in the planktonic phase [11].