Hyaluronic Acid and Bioactive Peptides

Hyaluronic acid: Definition and function

Hyaluronic acid is a polysaccharide glycosaminoglycan (GAG) produced by fibroblasts and found in the extracellular matrix (ECM). Researchers of hyaluronic acid found HA to consist of a vast number of configurations and shapes depending upon its molecular size, sodium concentration, and pH level. (1) It is produced by specific enzymes found in the inner surface of cell membranes called hyaluronic synthases (HAS). This is also the site that synthesizes hyaluronic acid and extracts it through the structure and finally into the extracellular space. (3)

In the dermis, the fibroblast cells produce collagen, glycosaminoglycans (GAGs), reticular and elastic fiber. Hyaluronic acid is considered to be a type of GAG that promotes collagen synthesis, repair, and hydration. GAGs provide the structural integrity in the extra-cellular matrix (ECM) which is an interwoven mesh of fibrous proteins and glycosaminoglycans. Water is attracted and binds to GAGs and contains 1,000-fold more volume of water facilitating ECM space and tissue hydration. (2)

According to one research finding, fifty percent of the body’s hyaluronic acid is found primarily in the skin. Hyaluronic acid is also found in joints (synovial fluid), portions of the eye, umbilical cord, lungs, heart valves and all tissues and fluids of the body. HA is also present on the inner surface of the cell’s membrane and is able to be transferred out of the cell during biosynthesis. However, the predominant component of the ECM is hyaluronic acid. The average 154-pound person has 15 grams of hyaluronic acid in the body, one-third of which is recycled and synthesized every day. (2) Another study states that HA provides cellular “cues” or signals through receptors to regulate inflammation and tissue repair. (3)

Understanding molecular weight in HA

Molecular weight has become one of the most confusing components regarding HA. While different weights are functional within the skin, it is important to ascertain how the skin, as an organ, utilizes or functions when present.

One important function of HA is to provide both structure and regulation. (3) Controlling the integrity of tissues, cellular inflammatory responses as well as recognizing smaller fragmented HA is part of the cell’s regulatory role. This regulatory component is constantly working towards homeostasis. When inflammation occurs, cells are immediately triggered to respond. The production of increased HA has to keep pace with the degradation and turnover; otherwise, unwanted skin conditions occur. (4)

Low molecular weight HA is considered to be 20 kDa. Research has shown that this weight inhibits lipid peroxidation and has superior radical scavenging activity. It is also found to be pro-inflammatory and is associated with premature aging. Other research reports that low molecular weight HA has the ability to increase fibrosis and is found to cause cancer cells to hijack other cells for the purpose of growth, invasion and metastatic spread. (3) However, the low molecular weight HA of 50 kDa is considered to be safe (2).

High molecular weight HA is considered to be over 800 kDa and is shown to be space filling. It is hydrating and inhibits the production of new blood vessels (anti-angiogenic) and can mediate tumor resistance. (2)

The degradation of HA into smaller fragments is called fragmented HA. This event usually occurs after an injury where reactive oxygen damage is present or when low levels of pH occur on the skin (chemical peels with micro-needling). (3)
According to one study, HA is able to penetrate regardless of its molecular weight. (2)

The findings of this study suggest that HA has the ability to penetrate through the epidermis passively, but may be facilitated by active transport.

Practitioners may have implemented modalities to assist with the transport of HA without fully knowing the molecular weight and the conditions it causes within the skin. Another study reports that dermal absorption can occur based on carriers, penetration enhancers and molecular size. (3)

According to Dr. Lance Setterfield, HA is used in fillers to add volume. The HA used in this treatment is more expensive because a stabilizing component through crosslinking has been added. It is important to note that cosmeceuticals do not add this component to their products, resulting in HA lasting less than a day in the skin. (4) Therefore, some professionals are resorting to micro-needling modalities to apply topical HA into the skin to provide increased trans-dermal delivery. However, this modality produces yet another problem.

During micro-needling, according the Setterfield, HA is degraded by the needles and the natural enzymes within a day or two because it triggers an enzyme called hyaluronidase. This enzyme breaks down hyaluronic acid. (4) In addition to this trigger, large molecular weight HA promotes cellular signals through their receptors to then regulate inflammation and tissue repair.

Bioactive peptides as a natural solution to HA

Bioavailable peptides are a viable solution to produce HA naturally. Peptides, if bioavailable, are able to encourage HA production in the ECM through hyaladherins. Hyaladherins are proteins or peptides that function as cell communicators. These hyaladherins are capable of binding to hyaluronic acid, providing cellular adhesion. (3) In the article, “Signaling Peptides and Skin Strength,” the term adherins was referred to as structures essential for the development of connective tissue. This connective tissue provides structure and strength to the skin. Hyaladherins are similar to adherins because they provide structure and hydration to the skin. Additionally, bioavailable peptides have the ability to attach to the cell’s receptor site. As natural cell communicators, peptides can signal the cell to perform a very particular function. In this case, the signal or message would be to synthesize hyaluronic acid. During the biofeedback loop, homeostasis involves, recognizing the smaller hyaluronic acid fragments (byproducts of degradation of the large native molecules) as distress signals and the need to create more normal hyaluronic acid.

According to the authors of “Hyaluronic Acid,” the most dramatic change in aging skin is the marked disappearance of epidermal hyaluronic acid. This provides a significant opportunity for the use of bioactive peptides without disrupting the homeostasis, the cellular structure and regulation.