The most influen al factor in the poor healing of chronic ulcers is replica ve senescence of fibroblasts that are unresponsive to TGF-β1 s mula on. Cellular replica ve senescence can be induced by cul va ng normal human dermal fibroblasts (HDFs) in a serum-starved medium. In addi on, increasing microenviroment mechanical forces by hyaluronic acid can ameliorate the TGF-β1 signaling of these senescent cells. One of natural resources of hyaluronic acid is bovine vitreous gel. In order to evaluate the effect of bovine-vitreous gel on replica ve senescence of fibroblasts, we used various levels of bovine vitreous gel diluted in Dulbecco's modified Eagle's medium to s mulate cellular ac vi es of serum-starved HDFs. Those cellular ac vi es were compared to the control media, standardized hyaluronic acid, and to normal HDFs. Our results show that replica ve senescence of HDFs treated with 50% bovine vitreous gel exhibited a significantly higher prolifera on index, migra on rate, and collagen deposi on than those cultured in control media, and they displayed an equal level of cellular ac vity with the HDFs exposed only to standardized hyaluronic acid. We concluded that bovine vitreous gel can be used to s mulate replica ve senescence of HDFs and therefore a poten al candidate material to s mulate healing of chronic ulcers.