Corneal epithelial defects usually heal within 48 hours. However, It is difficult to cure persistent corneal epithelial defect and chronic corneal ulcer with traditional therapy. The healing of corneal epithelium depends largely on the remodeling of extracellular matrix(ECM). Heparin sulfate (HS) is an important component of the ECM. It can specifically bind to matrix proteins, growth factors and cytokines, thus protecting them from proteolysis and facilitating tissue healing. In recent years, matrix regenerating agents (RGTA) consisting of heparan sulfate mimetic polymers has been gradually applied on clinical practice to promote corneal epithelial wound healing. RGTA is a pure bioengineering polymer that can completely resist the degradation of heparanase. It can replace the enzymatically hydrolyzed HS in damaged tissues, so as to reconstruct the stable environment in ECM. Clinical studies show that RGTA can effectively treat refractory corneal ulcer and is a promising new method.(Int Rev Ophthalmol, 2021, 45: 322-325)