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In vivo stimulation of de novo collagen production caused by cross-linked hyaluronic acid dermal filler injections in photodamaged human skin.

by Wang F, Garza LA, Kang S, Varani J, Orringer JS, Fisher GJ, Voorhees JJ
Archives of dermatology.

Article Abstract:

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.

Restylane and procollagen growth

By: Anonymous - Wed 5/16/2007 PM
Here is an interesting bit from the Q4 2006 Medicis Earnings Conference Call - Final:

http://www.paymentprotectioninsurancecover.co...

MARK PRYGOCKI: Obviously Professor Voorhees and his team performed some very elegant experiments, that I think elucidated some of the contributions that Restylane can make in rejuvenation of the skin. Certainly, we do not have a marketing plan around these data. This was a scientific experiment. It was done very elegantly and had statistical significance. It was published in a refereed, in fact, a prestigious medical journal and was the subject of the continuing medical education program from that journal for the month that it was published. So I think we're very, very pleased that professionals will have access to the data, the assumptions that underlie it and the conclusions of the authors really relating to the mechanism of action of Restylane. So I think all that is very positive.

My guess is that they'll be very significant dissemination of those scientific data within the professional community, through continuing medical education, through papers undoubtedly this will stimulate some more research. So it was a very important finding. And as was several clinicians were quoted in the lay press basically making the point that they have believed all along that progressive injections of Restylane can be spaced further apart, in their observation, we're making no claim about this ourselves. And they believe that this provides a basis for the view that something is happening beyond the introduction of Restylane Hyaluronic Acid into the skin. So I think it's very positive. There's undoubtedly a lot more research that will emerge about Restylane and the contributions that it makes, we believe uniquely, to facial rejuvenation.

In terms of other products, I really wouldn't elect to comment on that except to say what the investigators have said. They did this work with Restylane. There are differences among Hyaluronic Acid products as relates to structure, cost linking lift, all those sorts of things which predictably could influence very importantly the outcome of these kinds of studies. There are other materials as well that are used in facial aesthetics. There are no data on any of these products, at least that we're aware of in this connection. So we have data about Restylane. There is no data about these other products. People can speculate as they like. But as Professor Voorhees has said publicly, the only product studied in the study was Restylane. There are significant differences among these products and there's no reason to conclude that the activity and mechanism reported for Restylane would be applicable to any other products.

In vivo stimulation of de novo collagen production caused by cross-linked hyaluronic acid dermal filler injections in photodamaged human skin.

By: Anonymous - Wed 5/16/2007 AM
This article suggests that Restylane induces collagen. Per disclosures, Medesis only donated Restylane for the study... and the authors where not paid for the study. There is "no financial disclosure" for the article. I hope that is true...

In either case, skin reacts to hyaluronic acid by making new collagen via fibroblasts. They look at pro-collagen gene expression, and stain for C-terminal and N-terminal epitopes of type I procollagen.

Is this true? A follow up would be wonderful if photographs could be provided that show that after multiple injections of hyaluronic acid fillers have long lasting results. Secondly, would love to see hyaliform, juvederm, and captique in the same study. Finally, where these parameters examined with other fillers? Do all fillers (even non-Hyaluronic acid) cause these effects due to tissue trauma/stimulation/ stretch? Lasers?

Clinically I have not observed this to be true. I'm sure this will not prevent this article to appear in the Restylane marketing literature.
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