Bioengineered and functionalized silk proteins accelerate wound healing in rat and human dermal fibroblasts

Abstract

Wound healing is an intrinsic process directed towards the restoration of damaged or lost tissue. The development of a dressing material having the ability to control the multiple aspects of the wound environment would be an ideal strategy to improve wound healing. Though natural silk proteins, fibroin, and sericin have demonstrated tissue regenerative properties, the efficacy of bioengineered silk proteins on wound healing is seldom assessed. Furthermore, silk proteins sans contaminants, having low molecular masses, and combining with other bioactive factors can hasten the wound healing process. Herein, recombinant silk proteins, fibroin and sericin, and their fusions with cecropin B were evaluated for their wound-healing effects using in vivo rat model. The recombinant silk proteins demonstrated accelerated wound closure in comparison to untreated wounds and treatment with Povidone. Among all groups, the treatment with recombinant sericin-cecropin B (RSC) showed significantly faster healing, greater than 90% wound closure by Day 12 followed by recombinant fibroin-cecropin B (RFC) (88.86%). Furthermore, histological analysis and estimation of hydroxyproline showed complete epithelialization, neovascularization, and collagenisation in groups treated with recombinant silk proteins. The wound healing activity was further verified by in vitro scratch assay using HADF cells, where the recombinant silk proteins induced cell proliferation and cell migration to the wound area. Additionally, wound healing-related gene expression showed recombinant silk proteins stimulated the upregulation of EGF and VEGF and regulated the expression of TGF-β1 and TGF-β3. Our results demonstrated the enhanced healing effects of the recombinant silk fusion proteins in facilitating complete tissue regeneration with scar-free healing. Therefore, the recombinant silks and their fusion proteins have great potential to be developed as smart bandages for wound healing.

Effects of sericin and egg white on the inflammation of damaged skin in mice

“…The results of wound healing assays (figure 2) indicated that the mixture was more effective in wound healing than sericin alone. After 12 days, the wound recovery ratio of the EW + S-M group reached the highest (87.1%), which was a little lower than it of the wound treated with recombinant sericin-cecropin B (93%) reported by Manoharan et al [46]. Our result was also similar to it of wound treated with lysozyme separated from EW.…”

Silk Sericin and Its Composite Materials with Antibacterial Properties to Enhance Wound Healing: A Review

“…Bacterial metabolites can also cause leukocyte dysfunction [ 9 ], which inhibits migration of epidermal cells and keratinocytes [ 10 ]. For the treated group with SS-based antimicrobial dressing, pathogenic bacteria proliferation was significantly inhibited and it can promote wound healing through hemostasis, anti-inflammation, cell proliferation and angiogenesis [ 34 , 66 , 67 , 80 , 141 , 142 , 143 ]. In particular, SS-based antimicrobial materials are favorable for hemostasis through increasing the activity of FXIIa (the initiator of the coagulation cascade) and FIIa (the final thrombin in the coagulation cascade) [ 66 ].…”

“…The dressings also has anti-inflammatory properties through down-regulating pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-17 [ 144 ] as well as synthase enzymes involved in the inflammatory process, including COX-2 (cyclooxygenase) and iNOS (inducible nitric oxide synthase) [ 142 ] and increasing the anti-inflammatory cytokine IL-10 [ 141 ]. Inhibition of pathogenic bacteria will increase growth factor secretion and further promote cell proliferation, migration and angiogenesis [ 34 , 143 ].…”