Evaluation of the Modification Effects of Heparin/Dalteparin on Silk Fibroin Structure and Physical Properties for Skin Wound Healing

Abstract

We have developed a functionalized silk fibroin (BSF) that can serve as an improved fundamental material for dressings by specifically capturing growth factors secreted during the healing process and supplying them to cells accumulated in the wound area to enhance the tissue regeneration efficiency. When considering the design of heparin-modified BSF, there is a difficulty with binding to high-molecular-weight polysaccharides without disrupting the hydrophobic crystalline structure of the BSF. In this study, a low-molecular-weight pharmaceutical heparin, dalteparin, was selected and cross-linked with the tyrosine residue presence in the BSF non-crystalline region. When targeting 3D porous applications like nanofiber sheets, as it is crucial not only to enhance biological activity but also to improve handling by maintaining stability in water and mechanical strength, a trade-off between improved cell affinity and reduced mechanical strength depending on crystalline structure was evaluated. The use of dalteparin maintained the mechanical strength better than unfractionated heparin by reducing the effect on disturbing BSF recrystallization. Film surface hydrophilicity and cell proliferation induction were significantly higher in the dalteparin group. For BSF functionalization, using purified heparin was an effective approach that achieved a balance between preserving the mechanical properties and induction of tissue regeneration, offering the potential for various forms in the future.