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Hyaluronic acid (HA) gels have been used as filler material in the aesthetic field. Although the native HA molecule is without specificity of species and organs, synthetic cross-linked gels have differences in chemical composition and three-dimensional structure. Different technologies are employed in cross-linking, and the products have varying rheological properties.To determine whether the gels with differing chemical composition have differing histologic behavior when injected into human skin to determine if the histology changes after 14 days of implantation.Human volunteers consented to having controlled placement of HA intradermally into forearm or buttock skin. The trials were conducted in a single clinic in association with the Hôpitaux Universitaires de Genève, Geneva, Switzerland. The biopsies were taken immediately after implantation of the product and at day 14. Standard paraffin sections were prepared and stained with hematoxylin and eosin and Alcian blue and examined by an independent pathologist.Results show that each type of HA has a predictable histologic behavior in the skin. Biphasic gel has demonstrated deposition in big pools, often deep in the reticular dermis. The pools compress the collagen fibers. The papillary dermis and superficial reticular dermis are free of HA. Monophasic monodensified gels show large pools of hyaluronans throughout all the thickness of the reticular dermis. This material breaks up the collagen fibers of most of the dermal plane. The papillary dermis is free of exogenous hyaluronans. Monophasic polydensified cohesive gel penetrates into the dermis in a diffuse, evenly distributed manner, except in the papillary dermis, which remains free of exogenous material.The different types of cross-linked HA have different behaviors in the dermis immediately after their injection. The patterns are consistent between patients and are predictable. These histologic patterns do not change when biopsies are examined at 2 weeks.Dr. Flynn serves as a researcher for Merz.