Silkworm Silk Matrices Coated with Functionalized Spider Silk Accelerate Healing of Diabetic Wounds

Abstract

Complex cutaneous wounds like diabetic foot ulcers represent a critical clinical challenge and demand a large-scale and low-cost strategy for effective treatment. Herein, we use a rabbit animal model to investigate efficacy of bioactive wound dressings made up of silk biomaterials. Nanofibrous mats of Antheraea assama silkworm silk fibroin (AaSF) are coated with various recombinant spider silk fusion proteins through silk–silk interactions to fabricate multifunctional wound dressings. Two different types of spider silk coatings are used to compare their healing efficiency: FN-4RepCT (contains a cell binding motif derived from fibronectin) and Lac-4RepCT (contains a cationic antimicrobial peptide from lactoferricin). AaSF mats coated with spider silk show accelerated wound healing properties in comparison to the uncoated mats. Among the spider silk coated variants, dual coating of FN-4RepCT and Lac-4RepCT on top of AaSF mat demonstrated better wound healing efficiency, followed by FN-4RepCT and Lac-4RepCT single coated counterparts. The in vivo study also reveals excellent skin regeneration by the functionalized silk dressings in comparison to commercially used Duoderm dressing and untreated wounds. The spider silk coatings demonstrate early granulation tissue development, re-epithelialization, and efficient matrix remodelling of wounds. The results thus validate potential of bioactive silk matrices in faster repair of diabetic wounds.

<p>Potential Applications of Nanomaterials and Technology for Diabetic Wound Healing</p>

“… [ 85 ] Spider silk fusion proteins Nanofibrous mats of AaSF Efficient matrix remodelling of wounds. [ 93 ] Heparin or bemiparin CS hydrogels Improved diabetes-associated impaired wound healing. [ 87 ] Nucleic acids tFNAs Antioxidant activity via the Akt/Nrf2/HO-1 signaling pathway.…”

“… 92 Nanofibrous mats of Antheraea assama silkworm silk fibroin are coated with various recombinant spider silk fusion proteins through silk–silk interactions to fabricate multifunctional wound dressings. 93 …”

Spider Silk for Tissue Engineering Applications

“…In recent studies presented by Chouhan et al [81] and Liu et al [82], recombinant spider silk proteins were genetically modified with a motif from fibronectin to promote cell adhesion. Silk fibroin from silkworms was processed into nanofibrous mats and microporous scaffolds, and those were coated with the recombinant spider silk fusion protein (FN-4RepCT (FN-4RC)) ( Figure 8).…”

Nanotechnology Approaches in Chronic Wound Healing

“…104 Li et al prepared nanofiber dressing of SF encapsulating microparticles loaded with insulin. 105 Insulin stimulates keratinocyte and endothelial cell proliferation and migration, promoting wound reepithelialization and vascularization. These authors observed that the dressing improved the wound healing in diabetic rats due to a sustained release of the insulin during the wound healing progress.…”

“…When mats were coated with both spider silk proteins, they had a faster wound healing, improved granulation, angiogenesis, collagen deposition, and reepithelialization than the uncoated or one single coat in diabetic wounds. 105 SF scaffolds were also used as skin substitutes, by seeding human adipose-MSCs on them. 106 Interestingly, when the scaffolds were decellularized they were almost as effective as the seeded scaffolds in the treatment of diabetic wounds.…”