2‐kDa hyaluronan ameliorates human facial wrinkles through increased dermal collagen density related to promotion of collagen remodeling

BACKGROUND/AIMS: Hyaluronan (HA) oligosaccharides are involved in several biological processes, primarily collagen remodeling and wound healing. Collagen remodeling is retarded in aging skin and causes wrinkles. The aim of this study was to evaluate the effect of 2‐kDa HA oligosaccharides (HA2k) on wrinkles by permeation through the stratum corneum and promotion of collagen remodeling. METHODS: A 3D skin model and excised human skin were used to evaluate the permeation of fluorescein‐labeled HA2k. The effect of HA2k on collagen metabolism was evaluated by measuring the protein level of type 1 pro‐collagen (COL1A1) and matrix metalloproteinase‐1 (MMP‐1) in the 3D skin model. 0.1% HA2k solution and vehicle control was applied to the human forearm for 8 weeks to evaluate dermal collagen density. To evaluate the effect of HA2k on depth of facial wrinkles, a randomized controlled trial was conducted with 0.1% HA2k lotion and vehicle lotion for 8 weeks. RESULTS: HA2k was confirmed to permeate through the stratum corneum by fluorescent microscopy. Both COL1A1 and MMP‐1 were upregulated by HA2k application in a 3D skin model culture. The collagen density was higher for the HA2k‐treated forearm than for the vehicle control‐treated forearm after 4 weeks. The maximum wrinkle depths in the nasolabial fold and crow's feet area were significantly shallower in the HA2k lotion group than in the control group. CONCLUSION: HA2k permeated the stratum corneum, activated collagen synthesis and degradation simultaneously, and ameliorated wrinkles.