The present invention discloses a composite collagen sponge and the preparation method thereof. The composite collagen sponge comprises collagen, cell growth factors, and a protecting agent, and has a water absorption capacity of more than 52 times. The preparation method includes a cation chromatographic purification step and a two-stage inactivation step consisting of organic solvent/detergent virus inactivation and dry heat virus inactivation. The composite collagen sponge obtained by the method of the present invention not only improves the safety and performance of the product in clinical applications, but also ensures the stability and the bioactivity throughout the effective life of the product.
