Impaired wound healing can lead to local hypoxia or tissue necrosis and ultimately result in amputation or even death. Various factors can influence the wound healing environment, including bacterial or fungal infections, different disease states, desiccation, edema, and even systemic viral infections such as COVID-19. Silk fibroin, the fibrous structural-protein component in silk, has emerged as a promising treatment for these impaired processes by promoting functional tissue regeneration. Silk fibroin’s dynamic properties allow for customizable nanoarchitectures, which can be tailored for effectively treating several wound healing impairments. Different forms of silk fibroin include nanoparticles, biosensors, tissue scaffolds, wound dressings, and novel drug-delivery systems. Silk fibroin can be combined with other biomaterials, such as chitosan or microRNA-bound cerium oxide nanoparticles (CNP), to have a synergistic effect on improving impaired wound healing. This review focuses on the different applications of silk-fibroin-based nanotechnology in improving the wound healing process; here we discuss silk fibroin as a tissue scaffold, topical solution, biosensor, and nanoparticle.

Acute respiratory distress syndrome (ARDS) has approximately 40% in-hospital mortality, and treatment is limited to supportive care. Pneumonia is the underlying etiology in many cases with unrestrained inflammation central to the pathophysiology. We have previously shown that CNP-miR146a, a radical scavenging cerium oxide nanoparticle (CNP) conjugated to the anti-inflammatory microRNA(miR)-146a, reduces bleomycin- and endotoxin-induced acute lung injury (ALI) by decreasing inflammation. We therefore hypothesized that CNP-miR146a would decrease inflammation in murine infectious ALI. Mice were injured with intratracheal (IT) MRSA or saline followed by treatment with IT CNP-miR146a or saline control. Twenty-four hours post-infection, bronchoalveolar lavage fluid (BALF) and whole lungs were analyzed for various markers of inflammation. Compared to controls, MRSA infection significantly increased proinflammatory gene expression (IL-6, IL-8, TNFα, IL-1β; p < 0.05), BALF proinflammatory cytokines (IL-6, IL-8, TNFα, IL-1β; p < 0.01), and inflammatory cell infiltrate (p = 0.03). CNP-miR146a treatment significantly decreased proinflammatory gene expression (IL-6, IL-8, TNFα, IL-1β; p < 0.05), bronchoalveolar proinflammatory protein leak (IL-6, IL-8, TNFα; p < 0.05), and inflammatory infiltrate (p = 0.01). CNP-miR146a decreases inflammation and improves alveolar–capillary barrier integrity in the MRSA-infected lung and has significant promise as a potential therapeutic for ARDS.

Inflammation and oxidative stress are implicated in the pathogenesis of Crohn’s disease. Cerium oxide nanoparticle (CNP) conjugated to microRNA 146a (miR146a) (CNP-miR146a) is a novel compound with anti-inflammatory and antioxidative properties. We hypothesized that local administration of CNP-miR146a would improve colitis in a 2,4,6-Trinitrobenzenesulfonic acid (TNBS) mouse model for Crohn’s disease by decreasing colonic inflammation. Balb/c mice were instilled with TNBS enemas to induce colitis. Two days later, the mice received cellulose gel enema, cellulose gel with CNP-miR146a enema, or no treatment. Control mice received initial enemas of 50% ethanol and PBS enemas on day two. The mice were monitored daily for weight loss and clinical disease activity. The mice were euthanized on days two or five to evaluate their miR146a expression, inflammation on histology, and colonic IL-6 and TNF gene expressions and protein concentrations. CNP-miR146a enema successfully increased colonic miR146a expression at 12 h following delivery. At the end of five days from TNBS instillation, the mice treated with CNP-miR146a demonstrated reduced weight loss, improved inflammation scores on histology, and reduced gene expressions and protein concentrations of IL-6 and TNF. The local delivery of CNP-miR146a in a TNBS mouse model of acute Crohn’s colitis dramatically decreased inflammatory signaling, resulting in improved clinical disease.