Fabrication of calcium phosphate surface-coated hyaluronic acid microparticles with improved in vivo degradation resistance for dermal filler applications

Abstract

Hyaluronic acid (HA)-based dermal fillers (DFs) have been extensively commercialized worldwide. However, they suffer from short in vivo residence time due to degradation via the hyaluronidase (HDase) enzyme. This study aimed to fabricate calcium phosphate (Ca₃(PO₄)₂, CaP)-coated HA microparticles (HA@CaP MPs) that can prolong the residence time of HA and suppress potential inflammation at the site of injection, thereby complementing skin atrophy. The synthesized HA@CaP MPs exhibited appreciable water retention capacity pertinent to maintain the skin moisture. As envisioned, the CaP-coating slowed down the enzymatic degradation rate (HA/DVS = 3:1, 5 % in 168 h), subsequently improving the lifespan of cross-linked HA MPs. In addition, the in vivo study on C57BL/6 mice revealed that HA@CaP MPs stimulate the biosynthesis of collagen by fibroblasts, increase skin volume, and remodel the skin extracellular matrix (ECM) essential to augment skin fine lines, wrinkles, and nasolabial folds (NLFs). Moreover, the HA@CaP MPs didn’t trigger significant inflammation at the site of injection - beneficial to improve patient compliance. In general, the biocompatible HA@CaP MPs displayed desirable propensities as a long-acting skin booster and deserve further rigorous investigations.