Urea is an endogenous metabolite, known to enhance stratum corneum hydration. Urea is not merely a passive metabolite, but a small-molecule regulator of epidermal structure and function. Recent studies show that urea is a small-molecule regulator of epidermal permeability barrier function and antimicrobial peptide expression after transporter uptake, followed by gene regulatory activity in normal epidermis, with therapeutic value to a number of skin diseases and traumatized skin (Grether-Beck et al, 2014).
Aquaporins, the so-called water channels of the skin, form tetramers in the cell membrane, with each monomer acting as a channel. Interestingly, one of the tetramers is a channel called aquaporin 3, which is expressed in skin cells. Aquaporin 3, called an aquaglyceroporin, transports small neutral molecules such as glycerol along with the water to the inside of the cell. Studies show that skin lacking either the aquaporin3 channel, or devoid of glycerol, exhibit dryness and flaking, and impaired healing (Qin et al, 2011).
A major component of the extracellular matrix (ECM), hyaluronic acid contributes significantly to cell proliferation and migration. Hyaluronic acid (HA) is a polysaccharide that belongs to the glycosaminoglycan family and consists of a basic unit of two sugars, glucuronic acid and N-acetyl-glucosamine. Many studies have shown that the topical application of HA is beneficial to healing many types of wounds, including trauma, burns, and diabetic ulcers (Neuman et al, 2015).
Collagen is the major protein of the extracellular matrix (ECM), comprising 25% of the total protein in the body and 70% to 80% of skin (dry weight). Wounds, especially chronic wounds exhibit an elevated level of matrix metalloproteinases (MMPs). Elevated levels of MMPs not only degrade nonviable collagen but also viable collagen. In addition, fibroblasts in a wound may not secrete sufficient levels of MMP inhibitors (TIMPs) to control the degrading activity of MMPs. This disruption of homeostasis may prevent the formation of the scaffold needed for cell migration and ultimately prevent the reformation of the extracellular matrix (ECM) and granulation tissue. Collagen based wound dressings are uniquely suited to address the issue of elevated levels of MMPs by acting as a ‘sacrificial substrate’ in the wound. Thus, the collagen in the dressing acts as a substrate for the over activity of the MMPs. Further, collagen breakdown products are chemotactic for a variety of cell types required for the formation of granulation tissue, and have the ability to absorb wound exudates and maintain a moist wound environment (Chattopadhyay and Raines , 2014).