Concentration-Dependent Rheological Properties of Atelocollagen Are Associated with Fibroblast Mechanotransduction and Collagen Remodeling in Aged Skin.

Injectable collagen biomaterials are used to modify the dermal extracellular matrix in aged skin; however, whether concentration-dependent rheological differences are associated with distinct fibroblast responses remain unclear. We compared 3% and 6% atelocollagen (AtCOL) and examined three mechanobiological programs: (i) integrin (ITG) α5β1-ERK-cyclin D1 signaling related to proliferation; (ii) ITGβ1-FAK-YAP signaling related to matrix synthesis; and (iii) ITGα11β1/Tensin-1-positive fibrillar adhesion related to collagen assembly. Under the tested oscillatory shear conditions, 6% AtCOL displayed higher storage modulus (G'), loss modulus (G″), and complex viscosity, together with a lower tan δ, than 3% AtCOL. In aged mouse skin, the 6% formulation was associated with greater increases in ITGα5, pERK1/2, cyclin D1, PCNA, pFAK, nuclear YAP, COL1A1, COL3A1, ITGα11β1/Tensin-1 co-expression signal, collagen type I/III ratio, collagen type I fiber bundle width, mature collagen content, dermal collagen density, and an instrument-derived skin elasticity index, while MMP1, MMP2, and MMP9 were reduced. In an H2O2-induced fibroblast senescence model, ITGβ1 knockdown attenuated AtCOL-associated proliferative, matrix-synthetic, and fibrillar-adhesion responses. Complementary ITGβ1 overexpression produced directionally concordant increases in ITGA11 expression, relative fibroblast proliferation, COL1A1, and COL3A1 and decreases in MMP1, MMP2, and MMP9. Collectively, these findings are consistent with a concentration-dependent, ITGβ1-centered mechanotransduction model linking fibroblast proliferation, matrix synthesis, and collagen assembly within a single AtCOL system.