Document Detail


In vivo stimulation of de novo collagen production caused by cross-linked hyaluronic acid dermal filler injections in photodamaged human skin.
MedLine Citation:
PMID:  17309996     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: 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: Injection of cross-linked hyaluronic acid stimulates collagen synthesis, partially restoring dermal matrix components that are lost in photodamaged skin. We hypothesize that this stimulatory effect may be induced by mechanical stretching of the dermis, which in turn leads to stretching and activation of dermal fibroblasts. These findings imply that cross-linked hyaluronic acid may be useful for stimulating collagen production therapeutically, particularly in the setting of atrophic skin conditions.
Authors:
Frank Wang; Luis A Garza; Sewon Kang; James Varani; Jeffrey S Orringer; Gary J Fisher; John J Voorhees
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Publication Detail:
Type:  Controlled Clinical Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Archives of dermatology     Volume:  143     ISSN:  0003-987X     ISO Abbreviation:  Arch Dermatol     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-02-20     Completed Date:  2007-03-16     Revised Date:  2008-03-17    
Medline Journal Info:
Nlm Unique ID:  0372433     Medline TA:  Arch Dermatol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  155-63     Citation Subset:  AIM; IM    
Affiliation:
Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. frawang@umich.edu
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MeSH Terms
Descriptor/Qualifier:
Aged
Aged, 80 and over
Arm
Collagen Type I / drug effects*,  metabolism
Dermis / drug effects,  metabolism,  pathology
Female
Fibroblasts / drug effects,  physiology
Humans
Hyaluronic Acid / administration & dosage,  analogs & derivatives*,  pharmacology
Injections, Intradermal
Male
Middle Aged
Skin Aging / drug effects*,  pathology,  physiology
Tissue Inhibitor of Metalloproteinases / metabolism
Transforming Growth Factors / metabolism
Grant Support
ID/Acronym/Agency:
1K24 AR01259/AR/NIAMS NIH HHS; 5T32 AR007197/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Collagen Type I; 0/Restylane; 0/Tissue Inhibitor of Metalloproteinases; 76057-06-2/Transforming Growth Factors; 9004-61-9/Hyaluronic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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