Commentary: Rheological Evaluation of the Physical Properties of Hyaluronic Acid Dermal Fillers

When the first hyaluronic acid (HA) soft tissue filler (Restylane, Medicis) was approved by the U.S. Food and Drug Administration almost eight years ago, our focus was on its greater longevity compared to the collagen fillers we had worked with previously. While filler longevity remains a priority for patients and clinicians alike, we could not have predicted then that Restylane and subsequently approved HA products including Juvéderm Ultra and Ultra Plus (Allergan) and Perlane (Medicis) would bring far more than this isolated clinical benefit and ultimately catalyze a paradigm shift in philosophy. We have evolved from wrinkle-chasing to pan-facial volumization as our palette of fillers has expanded to encompass not only a variety of HA products but also calcium hydroxylapatite, poly-L lactic acid and polymethyl methacrylate.

Our early concepts of how to achieve the best results with each filler product stemmed from a process of clinical observation and deduction that brings to mind Albert Einstein's aphorism that the only source of knowledge is experience. It was clinical experience, and the intellectual curiosity this engendered, that led us into the laboratory to explore the physicochemical characteristics of fillers—most notably, the rheologic (flow-related) properties of elasticity and viscosity. HA filler products have much in common, but it became apparent to those using them that they also manifest significant differences in behavior—for example, in their degree of firmness and how much they spread after implantation. The seminal paper that provided a rationale for these differences, by Kablik and Monheit,¹ included an engaging analysis of each product's insoluble and soluble HA concentrations, elastic modulus (G prime) and capacity to absorb water after implantation. Dr. Gary Monheit has subsequently championed the study of rheology and other physicochemical characteristics as the key to furthering our clinical understanding of HA fillers.

The paper that appears in this issue of the Journal of Drugs in Dermatology² confirms that the Restylane/Perlane and Juvéderm families of HA products differ in their rheologic properties of gel elasticity and viscosity. It also demonstrates that all these products have a particulate component and that there is variation in the range and distribution of particle sizes. An understanding of these differences (which are based upon manufacturing methods) and how they can predict the clinical behavior of HA fillers is the foundation of rheologic tailoring—the process by which specific products can be selected to most efficiently achieve specific clinical objectives during facial rejuvenation.

While the level of evidence of in vitro studies is currently classified as lower than that of controlled clinical trials, it is nonetheless essential to appreciate that in vitro data, with the appropriate clinical correlation,are the foundation of an evidence-based approach towards current filler products and can markedly shorten the learning curve with new products. I feel that it is equally important for us to acknowledge, as Einstein did, the value of experience. As we continue to refine our strategies for soft tissue augmentation, science will guide us clinically, but the knowledge derived from our clinical experiences can be of equal utility in guiding our further scientific investigations.

Hema Sundaram, MD, FAAD
Medical Director, Sundaram Dermatology,
Cosmetic & Laser Surgery
Rockville, MD and Fairfax, VA

Disclosures: Dr. Sundaram has served as a consultant for, and has received grants and/or research support from: Medicis Aesthetics Corporation, Scottsdale, AZ; Mentor Worldwide LLC, Santa Barbara, CA; Merz Aesthetics, Inc., San Mateo, CA; Suneva Medical, Inc., San Diego, CA."

I would like to congratulate Mr. David Stocks, Dr. Sundaram, et al. for the excellent evaluation of rheology as a determinant of the physical properties of hyaluronic acid fillers. Though cross-linking is a major determinant in the physical characteristics of fillers, other factors include calibration—or, particle size—and concentration. These factors determine G' but also the unique characteristics found in the different manufactured hyaluronic acid fillers. An understanding of these properties allows us to choose the best particular filler for the clinical treatment site. Cross-linking and concentration can give us the stability and firmness of robust fillers for the tear trough or the softness and malleability best for the lips. The calibration or particle size can fulfill our need for deep lifting or volumizing. Understanding the physical parameters of each filler will help us use their differences for our clinical advantage in customizing our injection procedures.

Gary D. Monheit, MD
Total Skin & Beauty Dermatology Center, P.C.

Associate Clinical Professor
Department of Dermatology
Department of Ophthalmology
University of Alabama at Birmingham