Background: Hyaluronic acid (HA) formulations are used for aesthetic applications. Different cross-linking technologies result in HA dermal fillers with specific characteristic visco-elastic properties. Objective: Bio-integration of three CE-marked HA dermal fillers, a cohesive (monophasic) polydensified, a cohesive (monophasic) monodensified and a non-cohesive (biphasic) filler, was analysed with a follow-up of 114 days after injection. Our aim was to study the tolerability and inflammatory response of these fillers, their patterns of distribution in the dermis, and influence on tissue integrity. Methods: Three HA formulations were injected intradermally into the iliac crest region in 15 subjects. Tissue samples were analysed after 8 and 114 days by histology and immunohistochemistry, and visualized using optical and transmission electron microscopy. Results: Histological results demonstrated that the tested HA fillers showed specific characteristic bio-integration patterns in the reticular dermis. Observations under the optical and electron microscopes revealed morphological conservation of cutaneous structures. Immunohistochemical results confirmed absence of inflammation, immune response and granuloma. Conclusion: The three tested dermal fillers show an excellent tolerability and preservation of the dermal cells and matrix components. Their tissue integration was dependent on their visco-elastic properties. The cohesive polydensified filler showed the most homogeneous integration with an optimal spreading within the reticular dermis, which is achieved by filling even the smallest spaces between collagen bundles and elastin fibrils, while preserving the structural integrity of the latter. Absence of adverse reactions confirms safety of the tested HA dermal fillers.

Stern R, Maibach HI: Hyaluronan in skin: aspects of aging and its pharmacologic modulation. Clin Dermatol 2008;26:106-122.
Stern R: Devising a pathway for hyaluronan catabolism: are we there yet? Glycobiology 2003;13:105R-115R.
Romagnoli M, Belmontesi M: Hyaluronic acid-based fillers: theory and practice. Clin Dermatol 2008;26:123-159.
Richter AW, Ryde EM, Zetterstrom EO: Non-immunogenicity of purified sodium hyaluronic preparation in man. Int Arch Allergy Appl Immunol 1979;59:45-48.
Breithaupt AD, Custis T, Beddingfield F: Next-generation dermal fillers and volumizers. Cosmet Dermatol 2012;25:184-191.
La Gatta A, Schiraldi C, Papa A, De Rosa M: Comparative analysis of commercial dermal fillers based on crosslinked hyaluronan: physical characterization and in vitro enzymatic degradation. Polymer Degrad Stabil 2011;96:630-636.
Preston BN, Davies M, Ogston AG: The composition and physicochemical properties of hyaluronic acids prepared from ox synovial fluid and from a case of mesothelioma. Biochem J 1965;96:449-471.
Kablik J, Monheit GD, Yu LP, et al: Comparative physical properties of hyaluronic acid dermal fillers. Dermatol Surg 2009;35:302-312.
Tezel A, Fredrickson GH: The science of hyaluronic acid dermal fillers. J Cosmet Laser Ther 2008;10:35-42.
Bennett R, Taher M: Restylane persistent for 23 months found during Mohs micrographic surgery: a source of confusion with hyaluronic acid surrounding basal cell carcinoma. Dermatol Surg 2005;31:1366-1369.
Newman J: Review of soft tissue augmentation in the face. Clin Cosmet Invest Dermatol 2009;2:141-150.
Reinmuller J: Clinical study with monophasic polydensified hyaluronic acid filler shows: 81% success rate in the treatment of nasolabial folds. Dermatol News 2007;11:1-4.
Verpaele A, Strand A: Restylane SubQ, a non-animal stabilized hyaluronic acid gel for soft tissue augmentation of the mid- and lower face. Aesthetic Surg J 2006;26(suppl):S10-S17.
Bogdan Allemann I, Baumann L: Hyaluronic acid gel (Juvéderm™) preparations in the treatment of facial wrinkles and folds. Clin Interv Aging 2008;3:629-634.
Prager W, Wissmueller E, Havermann I, et al: A prospective, split-face, randomized, comparative study of safety and 12-month longevity of three formulations of hyaluronic acid dermal filler for treatment of nasolabial folds. Dermatol Surg 2012;38:1143-1150.
Pavicic T: Efficacy and tolerability of a new monophasic, double cross-linked hyaluronic acid filler for correction of deep lines and wrinkles. J Drugs Dermatol 2011;10:134-139.
Flynn TC, Sarazin D, Bezzola A, et al: Comparative histology of intradermal implantation of mono- and biphasic hyaluronic acid fillers. Dermatol Surg 2011;37:1-7.
Arlette JP, Trotter MJ: Anatomic location of hyaluronic acid filler material injected into naso-labial fold: a histologic study. Dermatol Surg 2008:34:S56-S63.
Maas CS, Bapna S: Pins and needles: minimally invasive office techniques for facial rejuvenation. Facial Plast Surg 2009;25:260-269.
Quan T, Wang F, Shao Y, et al: Enhancing structural support of the dermal microenvironment activates fibroblasts, endothelial cells, and keratinocytes in aged human skin in vivo. J Invest Dermatol 2013;133:658-667.
Porter S: The role of the fibroblast in wound contraction and healing. Wounds UK 2007;3:33-40.
You do not currently have access to this content.