Long-Term Effects of Collagen-Binding Mesenchymal Stem Cells Affinity Peptide on Skin Regeneration and Scar Formation Running Title: MSC Capturing Collagen and Skin Regeneration

Abstract The medical significance of mesenchymal stem cells (MSCs) is not only providing a promising strategy for cutaneous wound healing, but also bringing alternative for the patients whose wounds or burns were difficult to treat and heal. In our previous researches, we produced a fusion protein (Collagen/CBD-E7 peptide) which had high affinity to MSCs and then bound it to collagen scaffold with a CBD (collagen-binding domain). When applied to full-thickness skin defect porcine models, MSCs could be specifically raised to target area which helps accelerate coalescence at early stage. However, scar is an indispensable part of the tissue repair, arising after almost every dermal injury with abnormal appearance and functional disturbance. It usually takes one to three years for the scars to pale and mature. Thus, in this study, we focused on the structure repair of skin defect more than one year after the wounds healing. We found that at the 16w after operation, the proportion of collagen type III was more than collagen type I in Collagen/CBD-E7 peptide group, which indicates a higher healing quality comparatively. While at the 64w, the ratio between collagen type I and collagen type III reached a balance of natural skin tissues. In addition, cutaneous appendages were observed in Collagen/CBD-E7 peptide scaffold group at the 16w and 64w after surgery. From this point of view, the functional collagen scaffold treatments may be able to improve the cosmetic outcome of injury, burns or trauma, and scars are no longer an inevitable consequence of skin healing. This will also imply that humans would no longer be suffering from the scars caused by skin trauma, which is of significant orthopaedic meaning.