Cutaneous Regeneration Mechanism of β-Sheet Silk Fibroin in a Rat Burn Wound Healing Model

Abstract

Therapeutic dressings to enhance burn wound repair and regeneration are required. Silk fibroin (SF), a natural protein, induces cell migration and serves as a biomaterial in various dressings. SF dressings usually contain α-helices and β-sheets. The former has been confirmed to improve cell proliferation and migration, but the wound healing effect and related mechanisms of β-sheet SF remain unclear. We investigated the effects of β-sheet SF in vivo and in vitro. Alcohol-treated α-helix SF transformed into the β-sheet form, which promoted granulation formation and re-epithelialization when applied as lyophilized SF dressing (LSFD) in a rat burn model. Our in vitro results showed that β-sheet SF increased human dermal fibroblast (HDF) migration and promoted the expression of extracellular matrix (ECM) proteins (fibronectin and type III collagen), matrix metalloproteinase-12, and the cell adhesion molecule, integrin β1, in rat granulation tissue and HDFs. This confirms the role of crosstalk between integrin β1 and ECM proteins in cell migration. In summary, we demonstrated that β-sheet SF facilitates tissue regeneration by modulating cell adhesion molecules in dermal fibroblasts. LSFD could find clinical application for burn wound regeneration. Moreover, β-sheet SF could be combined with anti-inflammatory materials, growth factors, or antibiotics to develop novel dressings.

Effects of phase‐transited lysozyme on adhesion, migration and odontogenic differentiation of human dental pulp cells: An in vitro study

“…In vitro studies have demonstrated amyloid could stimulate cells to produce multiple cytokines and chemokines and induce cell migration through integrin‐ρ‐GTPase linked signalling (Connolly et al, 2011). Moreover, the β‐sheet structure of amyloid was also shown to enhance the motility of cells by increasing the expression of matrix metalloproteinase‐12 and integrin β1 (Chou et al, 2021). The positive effects of PTL on cell migration might partly attributed to these regulatory pathways involved as well as the upregulation of chemokines molecules such as integrin β1, on the other hand, the amyloid structure in PTL could capture proteins and other molecules, which create high concentrations of nutrients nearby and thus contribute to recruiting HDPCs.…”

Fabrication and Evaluation of Electrospun Silk Fibroin/Halloysite Nanotube Biomaterials for Soft Tissue Regeneration

“…The 3T3 cells deposited collagens I and IV in an open mesh-like pattern, while HDFs deposited these collagens as densely aligned strands that, in places, were crossed-linked. Interestingly, others found that dressings of lyophilized SF in a β-sheet form following ethanol treatment caused increased HDF migration and promoted the expression by HDFs of the ECM proteins, fibronectin, and collagen III [ 65 ]. Collagens I and IV and fibronectin are key ECM components of skin [ 66 ].…”

Silk Fibroin and Its Nanocomposites for Wound Care: A Comprehensive Review

“…43 Another study reported that the in vivo application of SF (in β-sheet form) to burn wounds promoted the expression of MMP-12, fibronectin, integrin-β1, and type III collagen in the granulation tissue. 46 Moreover, SF promoted the upregulation of three distinct pathways: phosphoinositide 3-kinase (PI3K/ AKT), mitogen-activated protein kinase kinase (MEK1), and c-Jun N-terminal kinase (JNK) resulting in the activation of induced c-Jun expression through downstream mechanisms and cell migration. Aykac et al reported that SF has a protective effect in a burn wound (rat model) by stimulating the apoptotic pathway.…”