Long-lasting and bioactive hyaluronic acid-hydroxyapatite composite hydrogels for injectable dermal fillers: Physical properties and in vivo durability.

Hyaluronic acid (HAc)-hydroxyapatite (HAp) composite hydrogels were developed to improve the biostability and bioactivity of HAc for dermal filler applications. Two kinds of HAc-HAp composite fillers were generated: HAcmicroHAp and HAc-nanoHAp composites. HAc-microHAp was fabricated by mixing HAp microspheres with HAc hydrogels, and HAc-nanoHAp was made by in situ precipitation of nano-sized HAp particles in HAc hydrogels. Emphasis was placed on the effect of HAp on the durability and bioactivity of the fillers. Compared with the pure HAc filler, all of the HAc-HAp composite fillers exhibited significant improvements in volumetric maintenance based on in vivo tests owing to their reduced water content and higher degree of biointegration between the filler and surrounding tissues. HAc-HAp composite fillers also showed noticeable enhancement in dermis recovery, promoting collagen and elastic fiber formation. Based on their long-lasting durability and bioactivity, HAc-HAp composite fillers have great potential for soft tissue augmentation with multifunctionality.