Effects of basic fibroblast growth factor combined with an injectable in situ crosslinked hyaluronic acid hydrogel for a dermal filler

摘要

Hyaluronic acid (HA) has been applied as a biomaterial for injectable dermal filler due to the unique viscoelastic property. Although HA derivatives are promising dermal filler materials, poor durability by degradation is the limitation of HA dermal filler. The chemical crosslinking of HA hydrogel is necessary to restrain the degradation rate. Herein, we present an injectable in situ HA hydrogel containing basic fibroblast growth factor (bFGF) crosslinked via a visible light-induced thiol-ene reaction. The thiol-ene reaction between thiolated HA (SH-HA) and methacrylated HA (MA-HA) is triggered by riboflavin phosphate with blue light (BL) exposure. The mechanical property, matrix degradation, and protein release of HA hydrogels were evaluated regarding SH-HA and MA-HA ratio. The HA hydrogels improve NIH/3T3 fibroblast proliferation and migration, and the bFGFs incorporated in HA hydrogel additionally induce the cell proliferation and scratch closure rate. In addition, the HA hydrogel precursor solution under a porcine skin forms hydrogel by transmitted BL through the skin, so the gelation can occur under the skin after injection. According to the results, the in situ crosslinked HA hydrogel is a promising injectable and long-lasting dermal filler that can deliver therapeutic factors.