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To determine whether endogenous synthesis of new extracellular matrix may contribute to the degree and duration of clinical benefits derived from crosslinked 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 re-vealed increased collagen deposition around the filler. Staining for prolyl-4-hydroxylase and the C-terminal and Nterminal epitopes of type I procollagen was enhanced at 4 and 13 weeks after treatment (PϽ.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 (PϽ.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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