Exploring Silk Sericin for Diabetic Wounds: An In Situ-Forming Hydrogel to Protect against Oxidative Stress and Improve Tissue Healing and Regeneration

Abstract

Chronic wounds are one of the most frequent complications that are associated with diabetes mellitus. The overproduction of reactive oxygen species (ROS) is a key factor in the delayed healing of a chronic wound. In the present work, we develop a novel in situ-forming silk sericin-based hydrogel (SSH) that is produced by a simple methodology using horseradish peroxidase (HRP) crosslinking as an advanced dressing for wound healing. The antioxidant and angiogenic effects were assessed in vitro and in vivo after in situ application using an excisional wound-healing model in a genetically-induced diabetic db/db mice and though the chick embryo choriollantoic membrane (CAM) assay, respectively. Wounds in diabetic db/db mice that were treated with SSH closed with reduced granulation tissue, decreased wound edge distance, and wound thickness, when compared to Tegaderm, a dressing that is commonly used in the clinic. The hydrogel also promoted a deposition of collagen fibers with smaller diameter which may have had a boost effect in re-epithelialization. SSH treatment slightly induced two important endogenous antioxidant defenses, superoxide dismutase and catalase. A CAM assay made it possible to observe that SSH led to an increase in the number of newly formed vessels without inducing an inflammatory reaction. The present hydrogel may result in a multi-purpose technology with angiogenic, antioxidant, and anti-inflammatory properties, while advancing efficient and organized tissue regeneration.

Sustainable Silk-Based Particulate Systems for the Controlled Release of Pharmaceuticals and Bioactive Agents in Wound Healing and Skin Regeneration

“…As previously stated, the silk of silkworms has multiple potential applications in biomedicine due to its good biocompatibility, mechanical properties, degradability, and plasticity. Several studies have shown that silk-based material dressings are more successful than traditional ones in the healing of skin wounds [ 34 , 159 , 160 , 161 ]. For instance, Batista-Silva et al [ 159 ] developed a novel in situ-forming SS hydrogel as an enhanced dressing for wound healing using a simple technology based on horseradish peroxidase crosslinking ( Figure 7 A).…”

“…Several studies have shown that silk-based material dressings are more successful than traditional ones in the healing of skin wounds [ 34 , 159 , 160 , 161 ]. For instance, Batista-Silva et al [ 159 ] developed a novel in situ-forming SS hydrogel as an enhanced dressing for wound healing using a simple technology based on horseradish peroxidase crosslinking ( Figure 7 A). The authors observed that the SS-hydrogels promoted wound closure and a decrease in granulation tissue compared to commercial Tegaderm TM dressing ( Figure 7 B).…”

“…The highest levels of antioxidants were obtained at 24 h, which could be attributed to the release of phenolic compounds. It should be noted that antioxidant activity can be an important factor in limiting the oxidation of inflammatory processes during healing and tissue regeneration events [ 159 ].…”

Emerging Antimicrobial and Immunomodulatory Fiber-Based Scaffolding Systems for Treating Diabetic Foot Ulcers

“…Silk sericin is a globular protein with remarkable biodegradability, biocompatibility, antioxidant capacity, and regenerative abilities, including faster wound healing abilities, accelerated cell proliferation, and a low inflammatory profile. Silk sericin is less explored than silk fibroin; however, fiber-based scaffolding systems for DFU care have already been engineered [ 59 , 63 ]. Indeed, Gilotra et al demonstrated the antioxidant potential of silk sericin without compromising cell viability and verified its ability to accelerate wound healing without triggering any inflammatory response [ 64 ].…”

Oral Administration Sericin-Curcumin Nanoconjugates Inhibits Inflammation and Epithelial-Mesenchymal Transition to Treat Renal Interstitial Fibrosis

“…Studies have shown that curcumin can inhibit EMT to reverse renal brosis progression [8], can effectively inhibit EMT via the TGF-β1 and Smad pathways [9] and may be used as an effective agent in additional treatments for RIF. Sericin is a complicated polypeptide that is extracted from home silkworm cocoons; agricultural scientists have reported that it has good biocompatibility and that its immunogenicity is negligible [10].…”