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Facial aging results from reduced biosynthetic activity of dermal fibroblasts and decreased deposition of extracellular matrix components, such as hyaluronic acid, a glycosaminoglycan responsible for skin hydration and turgidity. Exogenous hyaluronic acid injections provide a safe though short-term solution for facial rejuvenation. Using a rabbit model, the authors investigated residence time and tolerability of ACP gel, a new hyaluronic acid cross-linked derivative, compared with high-molecular-weight native hyaluronic acid currently used for facial rejuvenation (Ial System).ACP gel 1% and 2%, Ial System, and saline were intradermally injected into the backs of 12 New Zealand rabbits: six animals were used to follow volume maintenance and redness up to 10 days and the other six animals were euthanized at days 2, 6, 8, 10, 14, and 21 (one animal per time point) to histologically assess biocompatibility.ACP gel 2% had the longest residence time, showing a significantly better volume maintenance than the other samples, especially in the initial study period (71 percent of original volume versus 23 percent and 21 percent of ACP gel 1% and Ial System, respectively, at day 2). Macroscopically, no adverse events were observed in the treated animals. Histologic examination confirmed the absence of adverse events, persistent inflammation, tissue degeneration, or necrosis. ACP gel macrophage-mediated phagocytosis was more persistent with respect to the Ial System, consistent with its longer residence time.ACP gel 2% is a promising dermal biorevitalizer, characterized by a high safety profile and prolonged residence time in relation to native high-molecular-weight hyaluronic acid.