Hyaluronic acid: It’s not just for the skin

Whenever I think about hyaluronic acid (HA), my skin comes to mind. I’m not sure why, since I have neglected it for about 58 years, but I guess all those skin care commercials have really stuck with me.

HA is the main component of what gives our skin structure. It’s responsible for that plump and hydrated look. We hear so much about collagen, but hyaluronic acid is a part of what gives collagen its flexibility and also has many other benefits.

HA also plays an important role in various biological processes, such as cell signaling, morphogenesis, matrix organization, tissue hydration, lubrication, wound healing, regulating gene expression, and cell proliferation. It’s a naturally occurring glycosaminoglycan found in the connective tissue of all vertebrates and can also be produced by some fermenting-capable bacteria, which may sound gross but speaks to the biological necessity of this remarkable molecule.

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The commercialization of HA has become a booming business due to the ever-growing list of possible uses. A deep dive into the literature can be dizzying due to different names, molecular weights, and source organisms that have been optimized for production.

Key take-homes are that hyaluronan is the same thing as HA, commercial production is primarily from streptococcal species, and the molecular weight (MW) of HA in common topical formulations can vary.

The main differences between MWs are primarily that of skin penetration. HA with larger MW doesn’t penetrate the skin’s surface as deeply but can provide more hydration on the surface. HA with smaller MW can penetrate deeper into the skin, potentially delivering more noticeable results in terms of moisture retention and wrinkle reduction.

As we age, the natural production of collagen, elastin, and—yes—HA slows, causing the dry, thinner, wrinkled skin appearance common to older individuals. HA’s long list of benefits was first noticed in ophthalmology, and then moved to joint and skin diseases. From there, HA has steadily grown into a celebrity molecule in skin care and antiaging products.

More recently, HA has been investigated as a drug delivery device because of its unique hygroscopic properties, which allow it to stick to tissues naturally and deliver drugs or missing nutrients.

Because HA is naturally occurring in our tissues, it is part of the tissue turnover process that undergoes constant remodeling, effectively rendering all HA as a biodegradable product that can be broken down and eliminated from the body over time. It has also been shown to possess anti-inflammatory effects, which may contribute to its ability to reduce pain and swelling in arthritic joints. In addition, it promotes tissue regeneration and repair, making it useful in wound healing and tissue engineering applications.

Wound healing

In the body, hyaluronic acid is involved in every stage of wound healing as it can help regulate inflammation and stimulate tissue growth.¹ Scientists have noted its beneficial effects both immediately after an injury and in long-term wounds as well.

HA treatment has been reported to cause a 70% reduction in the surface area of wounds.² In part it’s done by protecting tissue from oxygen free-radical damage, acting as an antioxidant by scavenging reactive oxygen species.³ Since periodontal disease is essentially a wound and causes an imbalance between oxidant and antioxidants, it sounds like a great area in which to be utilized. When HA is used in conjunction with scaling and root planing, there are significant positive differences over scaling and root planing alone.^4,5

Antibacterial, ­anti-inflammatory, and oral ulcers

HA may have an antibacterial effect by inhibiting the growth and attachment of various microorganisms, including Staphylococcus aureus, Streptococcus mutans, Escherichia coli, and Pseudomonas aeruginosa.⁶

A high concentration of 1.0 mg/ml HA proved to have bacteriostatic effects for Actinobacillus actinomycetemcomitans, Prevotella oris, Staphylococcus aureus, and Propionibacterium acnes strains, which may prove beneficial in minimizing contamination of surgical wounds when used in guided tissue regeneration surgery.⁷

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An antibacterial effect of HA against Porphyromonas gingivalis (Pg) has been demonstrated by multiple laboratory studies in vitro, significantly inhibiting the growth and biofilm formation of Pg.^8,9 Additional research showed a significant reduction in the expression of multiple virulent genes in Pg including fimA, mfa1, hagA, rgpA, and hagA.¹⁰

A recent systematic review did conclude that HA did not demonstrate an additional benefit for lowering Pg in subgingival biofilms as an adjunct to nonsurgical therapy.¹¹ But, of course, more human studies are needed. Treatment with high molecular weight (HMW) HA may counteract the effects of Pg by altering cytokine production and help reduce inflammatory reaction due to Pg.

For treatment strategy, combinations of HMW HA with other agents can increase anti-inflammatory cytokines to balance out the pro-inflammatory cytokines, which may produce even better anti-inflammatory effects than HA alone. HA suppresses the production of some pro-inflammatory mediators such as metalloproteinases and interleukin-1β.¹² A randomized controlled trial not only proved to have positive effects on pocket depths but also in preventing the recolonization of some periodontal pathogens.¹³

A topical 0.2% HA has shown good results for aphthous ulcers, mucositis, and traumatic ulcers.^14-16 In 2002 the FDA approved sachets for the management of HA in oral mucositis associated with chemotherapy. Readily available on the market are gels with 0.2% hyaluronic with xylitol. There is some compelling evidence showing positive results for oral lichen planus.¹⁷

Bone regeneration and dental surgery

Several studies speak to the benefits of HA in implant healing and pain reduction and management of implant pathology.^18,19 HA-based hydrogels and microparticles can bind to metal implant surfaces and release bioactive components, resulting in better osteogenesis and osseointegration.²⁰

Deep periodontal defects treated with esterified HA in packed fibers demonstrated reduced probing depth after one year, and attachment gain was reported.²¹ Overwhelmingly, HA has shown considerable promise in implant recovery, ulcer and wound healing, and reducing periodontal pathogens and infections.

Interestingly, during the aging process in the mouth, the risk of gingivitis grows and with it comes degradation of HA, similar to what is seen in the skin. There are similarities in architecture, function, and cell signaling when comparing the oral mucosa to the skin.

There are many other molecules being investigated in oral care such as vitamin D, arginine, omega 3, and niacinamide, all of which are widely utilized in skin care with great antiaging benefits. The idea of using HA as a delivery system by combining it with other gentle oral antimicrobial agents that will enhance HA’s effectiveness sounds like a great combination to have in toothpastes and rinses. Oral medicine is making progress. I’m looking forward to seeing all of the advances in 2024.

Editor's note: This article appeared in the January/February 2024 print edition of RDH magazine. Dental hygienists in North America are eligible for a complimentary print subscription. Sign up here.

References

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3. Trabucchi E, Pallotta S, Morini M, et al. Low molecular weight hyaluronic acid prevents oxygen free radical damage to granulation tissue during wound healing. Int J Tissue React. 2002;24(2):65-71.
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10. Alharbi MS, Alshehri FA. High molecular weight hyaluronic acid reduces the expression of virulence genes fimA, mfa1, hagA, rgpA, and kgp in the oral pathogen Porphyromonas gingivalis. Pharmaceutics. 2022;14(8):1628. doi:10.3390/pharmaceutics14081628
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16. Lee JH, Jung JY, Bang D. The efficacy of topical 0.2% hyaluronic acid gel on recurrent oral ulcers: comparison between recurrent aphthous ulcers and the oral ulcers of Behçet’s disease. J Eur Acad Dermatol Venereol. 2008;22(5):590-595. doi:10.1111/j.1468-3083.2007.02564.x
17. Waingade M, Medikeri RS, Gaikwad S. Effectiveness of hyaluronic acid in the management of oral lichen planus: a systematic review and meta-analysis. J Dent Anesth Pain Med. 2022;22(6):405-417. doi:10.17245/jdapm.2022.22.6.405
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21. Vanden Bogaerde L. Treatment of infrabony periodontal defects with esterified hyaluronic acid: clinical report of 19 consecutive lesions. Int J Periodontics Restorative Dent. 2009;29(3):315-323.

Anne O. Rice, BS, RDH, CDP, FAAOSH, founded Oral Systemic Seminars after almost 30 years of clinical practice and is passionate about educating the community on modifiable risk factors for dementia and their relationship to dentistry. She is a certified dementia practitioner, a longevity specialist, a fellow with AAOSH, and a consultant for Weill Cornell Alzheimer’s Prevention Clinic, FAU, and Atria Institute. Reach out to Anne at anneorice.com.