Functionalized silk dental floss as a vehicle for delivery of bioactive minerals and ions to the tooth surface.

PURPOSE: To enable the commercially available silk dental floss to carry a series of desensitizing, alkalizing, and tooth strengthening pharmacons. METHODS: The hydroxy-groups of the serine and tyrosine residues of the commercial silk dental floss were exposed by degumming, and employed as the chemical anchors for the introduction of carboxy-groups to the surface. The affinity of the silk dental floss to a set of bioactive species was studied by SEM, EDS, and XFS. The acetylated silk was used as a control sample for the experiments elucidating the effect of the surface carboxy-groups on its affinity to a series of pharmacons. RESULTS: While unmodified silk has affinity to microcrystals of sodium carbonate, some affinity to hydroxyapatite particles and Sr2+, its carboxylation drastically increased the affinity to hydroxyapatite, Sr2+, Ca2+ and K+. The unmodified silk had some affinity to existing hydroxyapatite particles, but did not initiate the growth of hydroxyapatite on the surface. Carboxylation of silk enabled the growth of hydroxyapatite on its surface, and significantly increased its affinity to the existing hydroxyapatite particles. The unmodified silk had significant affinity to Zn2+, which exceeded its acylated derivatives. CLINICAL SIGNIFICANCE: The ability of the commercial and modified silk floss to carry a series of pharmacons makes them precursors for a series of new versatile materials with a potential for delivering small doses of bioactive agents in a targeted manner.

Sunitinib promotes myogenic regeneration and mitigates disease progression in the mdx mouse model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a lethal, muscle degenerative disease causing premature death of affected children. DMD is characterized by mutations in the dystrophin gene that result in a loss of the dystrophin protein. Loss of dystrophin causes an associated reduction in proteins of the dystrophin glycoprotein complex, leading to contraction-induced sarcolemmal weakening, muscle tearing, fibrotic infiltration and rounds of degeneration and failed regeneration affecting satellite cell populations. The α7ß1 integrin has been implicated in increasing myogenic capacity of satellite cells, therefore restoring muscle viability, increasing muscle force and preserving muscle function in dystrophic mouse models. In this study, we show that a Food and Drug Administration (FDA)-approved small molecule, Sunitinib, is a potent α7 integrin enhancer capable of promoting myogenic regeneration by stimulating satellite cell activation and increasing myofiber fusion. Sunitinib exerts its regenerative effects via transient inhibition of SHP-2 and subsequent activation of the STAT3 pathway. Treatment of mdx mice with Sunitinib demonstrated decreased membrane leakiness and damage owing to myofiber regeneration and enhanced support at the extracellular matrix. The decreased myofiber damage translated into a significant increase in muscle force production. This study identifies an already FDA-approved compound, Sunitinib, as a possible DMD therapeutic with the potential to treat other muscular dystrophies in which there is defective muscle repair.