Frank Wang

“Rejuvenation”: Injection of Filler into Photoaged Skin Stimulated Fibroblasts to Produce More Collagen Interview with:

Frank Wang

Dr. Frank Wang

Frank Wang MD
William B. Taylor Endowed Professor of Clinical Dermatology
Associate Professor, Dermatology
Associate Chair for Education
Assistant Program Director, Dermatology Residency Program
University of Michigan
Ann Arbor, Michigan What is the background for this study? How is the cross-linked hyaluronic acid obtained? Where was it injected?

Response: As the skin undergoes photoaging due to chronic exposure to ultraviolet light, it loses dermal collagen, which in turn leads to wrinkling, lines, and loss of support. The loss of collagen is, in large part, due to reduced function of the skin’s collagen-producing cells, dermal fibroblasts.

We wanted to investigate whether it was possible to reverse the decreased function of fibroblasts in photodamaged skin, by introducing a space-filling material into the dermis, injected CL-HA dermal filler. The CL-HA filler we used was donated to us for research purposes.

We performed injections of CL-HA into the mid-dermis (as is normally done when injected into the face) of severely photoaged forearm skin of human participants over the age of 60. We then examined skin samples at various time points, including 1, 2, 3 and 4 weeks and 3, 6, 9, and 12 months post-injection. What are the main findings?

Response:  We found that the injected filler is able to stimulate fibroblasts rapidly (by 1 week following injection) and for as long as 6-9 months. The filler was able to do this by “stretching” fibroblasts, which activated their ability to produce collagen. In turn, the collagen produced by fibroblasts accumulated in the dermis in a durable fashion – starting around 1 month and then continuing over at least 1 year (our longest time point in the study). What should readers take away from your report?

Response: Early on, immediately following CL-HA injection, improvement in appearance is mostly due to space-filling, or “volumization” of the skin from the physical presence of the injected filler material. However, as early as 1 month following injection, deposition of collagen in the dermis may begin to play a role, contributing to clinical effects of the filler. Over the course of a year, accumulation of dermal collagen continues and contributes more substantially to the clinical improvement. Based on the known properties of collagen, we would expect the new collagen to last a long time (many years), such that with each CL-HA injection a person receives, the future need for re-treatment may be reduced. Additionally, with continued injections over time, we would expect that less filler material or less frequent injections would achieve the same cosmetic improvement for an individual. What recommendations do you have for future research as a results of this study?

Response: We performed our work in individuals over the age of 60 years with substantially photodamaged skin. As dermal fillers are increasingly being used in younger individuals, we plan to investigate whether the same changes occur in adults ages 30-50 years. Is there anything else you would like to add? Any disclosures?

Response: The changes that we observed following CL-HA injection help to restore reduced dermal collagen and fibroblast function that occur with photoaging, “rejuvenating” skin at the cellular/molecular level. Our results demonstrate that changes that occur in the dermis with photoaging are not irreversible – they can be reversed by “stretching” of fibroblasts. In other words, fibroblasts in photoaged human skin retain their capacity for functional activation, including collagen production.

Any disclosures? For this study and all of our prior work, the manufacturer of the filler donated the CL-HA filler-containing syringes for research purposes, but the company was not involved in the design or conduct of our studies; the collection, management, analysis, and interpretation of any of our data; or in the preparation or review of any of our manuscripts.

Citation: Wang F, Do TT, Smith N, et al. Implications for cumulative and prolonged clinical improvement induced by cross-linked hyaluronic acid: An in vivo biochemical/microscopic study in humans. Exp Dermatol. 2024; 33:e14998. doi:10.1111/exd.14998


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Last Updated on February 19, 2024 by Marie Benz MD FAAD