Subcutaneous Application of a Gelatin/Hyaluronic Acid Hydrogel Induces the Production of Skin Extracellular Matrix

The development of injectable hydrogels with natural biopolymers such as gelatin (Ge) and hyaluronic acid (Ha) is widely performed due to their biocompatibility and biodegradability. The combination of both polymers crosslinked with N-Ethyl-N'-(3-dimethyl aminopropyl) carbodiimide hydrochloride (EDC) can be used as an innovative dermal filler that stimulates fibroblast activity and increases skin elasticity and tightness. Thus, crosslinked Ge/Ha hydrogels with different concentrations of EDC were administered subcutaneously to test their efficacy in young and old rats. At higher EDC concentrations, the viscosity decreases while the particle size of the hydrogels increases. At all concentrations of EDC, amino and carboxyl groups are present. The histological analysis shows an acute inflammatory response, which disappears seven days after application. At one and three months post-treatment, no remains of the hydrogels are found, and the number of fibroblasts increases in all groups in comparison with the control. In addition, the elastic modulus of the skin increases after three months of treatment. Because EDC-crosslinked Ge/Ha hydrogels are biocompatible and induce increased skin tension, fibroblast proliferation, and de novo extracellular matrix production, we propose their use as a treatment to attenuate wrinkles and expression lines.