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Objective To design and investigate the collagen sponge containing capsaicin according to the orthogonal experiment design.Collagen sponge containing 5% glycerin and 0.05% (w/w) capsaicin was chosen as the formulation.Methods The prepared capsaicin-collagen sponge was characterized by scanning electron microscopy (SEM), porosity, water uptake, drug release as well as degradation in vitro and in vivo.Results The sponge was a soft scaffold with porous structure and appropriate pore sizes (60~200μm).Porosity was about 114.46% (higher than 90%);Water uptake reached 1396%.The degradation test in vitro and in vivo demonstrated the collagen sponge was completely biodegradable and absorbed by the rats.Drug release data indicated capsaicin release from sponges was under non-Ficks diffusion.Capsaicin release was dependent on two simultaneous processes: the capsaicin diffusion through the system and the matrix swelling occurring at the same time.The porous structure could be beneficial for absorbing wound fluids, keeping the wound area dry, and enhancing oxygen supply to the wound.Conclusion The properties of high porosity, excellent water uptake ability, biodegradability,and sustained drug delivery system provided collagen sponge could be an ideal scaffold for skin tissue engineering.