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Derm News: 2007.8(9)

In Vivo Stimulation of De Novo Collagen Production Caused by Cross-linked Hyaluronic Acid Dermal Filler Injections in Photodamaged Human Skin

Arch Dermatol 2007;143:155-163
Frank Wang, MD; Luis A. Garza, MD, PhD; Sewon Kang, MD; James Varani, PhD; Jeffrey S. Orringer, MD; Gary J. Fisher, PhD; John J. Voorhees, MD
ABSTRACT

Objectives

To determine whether endogenous synthesis of new extracellular matrix may contribute to the degree and duration of clinical benefits derived from cross-linked hyaluronic acid dermal filler injections.

Design

In vivo biochemical analyses after filler injections.

Setting

Academic referral center.

Participants

Eleven healthy volunteers (mean age, 74 years) with photodamaged forearm skin.

Interventions

Filler and vehicle (isotonic sodium chloride) injected into forearm skin and skin biopsy specimens taken 4 and 13 weeks later.

Main Outcome Measures

De novo synthesis of collagen, the major structural protein of dermal extracellular matrix, was assessed using immunohistochemical analysis, quantitative polymerase chain reaction, and electron microscopy.

Results

Compared with controls, immunostaining in skin receiving cross-linked hyaluronic acid injections revealed increased collagen deposition around the filler. Staining for prolyl-4-hydroxylase and the C-terminal and N-terminal epitopes of type I procollagen was enhanced at 4 and 13 weeks after treatment (P<.05). Gene expression for types I and III procollagen as well as several profibrotic growth factors was also up-regulated at 4 and 13 weeks compared with controls (P<.05). Fibroblasts in filler-injected skin demonstrated a mechanically stretched appearance and a biosynthetic phenotype. In vitro, fibroblasts did not bind the filler, suggesting that cross-linked hyaluronic acid is not directly stimulatory.

Conclusions

Compared with controls, immunostaining in skin receiving cross-linked hyaluronic acid injections revealed increased collagen deposition around the filler. Staining for prolyl-4-hydroxylase and the C-terminal and N-terminal epitopes of type I procollagen was enhanced at 4 and 13 weeks after treatment (P<.05). Gene expression for types I and III procollagen as well as several profibrotic growth factors was also up-regulated at 4 and 13 weeks compared with controls (P<.05). Fibroblasts in filler-injected skin demonstrated a mechanically stretched appearance and a biosynthetic phenotype. In vitro, fibroblasts did not bind the filler, suggesting that cross-linked hyaluronic acid is not directly stimulatory.


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The Derm News service provided by the Editorial Consultants of Skin Therapy Letter© and its founding editor Dr. Stuart Maddin.