A novel human-like collagen hemostatic sponge with uniform morphology, good biodegradability and biocompatibility.

Biodegradable sponges, as a promising hemostatic biomaterial, has been clinically required over the past decades. Current hemostatic sponges are generally prepared by crosslinking and freeze-drying, but the quality control or biocompatibility is often unsatisfactory due to the freezing-caused morphological non-uniformity and the toxicity of raw materials or cross-linkers. The crosslinking often greatly retards the degradation of the sponges and thus affects the healing of the wound. In this work, we prepared a novel hemostatic sponge using human-like collagen and glutamine transaminase (non-toxic cross-linker) and optimized its morphology via "two-step" freezing instead of conventional "one-step" freezing. The resulting sponge showed a good biocompatibility in cytotoxicity and implantation tests and had a significant hemostatic effect in ear artery and liver injury models. Moreover, the sponge could be degraded high efficiently by several common enzymes in organisms (e.g. I collagenase, trypsase, and lysozyme), which means that the sponge can be easily digested by metabolism and can facilitate seamless healing. Finally, both the front and back of the sponge prepared via two-step freezing was more uniform in morphology than that prepared via one-step freezing. More importantly, two-step freezing can be used as a universal approach for preparation of diverse uniform biomaterials.