Melt-extruded biocompatible surgical sutures loaded with microspheres designed for wound healing.

Sutures are commonly used in surgical procedures and have immense potential for direct drug delivery into the wound site. However, incorporating active pharmaceutical ingredients into the sutures has always been challenging as their mechanical strength deteriorates. This study proposes a new method to produce microspheres-embedded surgical sutures that offer adequate mechanical properties for effective wound healing applications. The study used curcumin, a bioactive compound found in turmeric, as a model drug due to its anti-inflammatory, antioxidant, and anti-bacterial properties, which make it an ideal candidate for a surgical suture drug delivery system. Curcumin-loaded microspheres were produced using the emulsion solvent evaporation method with polyvinyl alcohol (PVA) as the aqueous phase. The microspheres' particle sizes, drug loading (DL) capacity, and encapsulation efficiency (EE) were investigated. Microspheres were melt-extruded with polycaprolactone and polyethylene glycol via a 3D bioplotter, followed by a drawing process to optimise the mechanical strength. The sutures' thermal, physiochemical, and mechanical properties were investigated, and the drug delivery and biocompatibility were evaluated. The results showed that increasing the aqueous phase concentration resulted in smaller particle sizes and improved DL capacity and EE. However, if PVA was used at 3% w/v or below, it prevented aggregate formation after lyophilisation, and the average particle size was found to be 34.32 ± 12.82 µm. The sutures produced with the addition of microspheres had a diameter of 0.38 ± 0.02 mm, a smooth surface, minimal tissue drag, and proper tensile strength. Furthermore, due to the encapsulated drug-polymer structure, the sutures exhibited a prolonged and sustained drug release of up to 14 d. Microsphere-loaded sutures demonstrated non-toxicity and accelerated wound healing in thein vitrostudies. We anticipate that the microsphere-loaded sutures will serve as an excellent biomedical device for facilitating wound healing.

Bilirubin oxidation provoked by nitric oxide radicals predicts the progression of acute cardiac allograft rejection.

Bilirubin, a strong intrinsic antioxidant, quenches free radicals produced under inflammatory conditions. The oxidized bilirubin metabolites, i.e. biopyrrins, are immediately excreted into urine and can indicate the intensity of oxidation in vivo. Our preliminary studies suggested the involvement of reactive nitrogen species (RNS) in generation of biopyrrins. However, little is known about biological significance of bilirubin oxidation by RNS. Here, we analyzed the correlation between bilirubin oxidation and nitric oxide (NO) radicals during rat acute cardiac allograft rejection. In allograft recipients, urinary biopyrrins steeply increased on day 3 prior to the increase in myocardial tissue damage marker, serum troponin-T. In contrast, no significant changes in urinary biopyrrins were evident in recipients of isografts or cyclosporine-A treated allografts. Urinary nitrotyrosine, a marker of oxidation by NO radicals also increased on day 3, while administration of a NO synthase inhibitor, N(G)-monomethyl-L-arginine apparently diminished the elevation of urinary biopyrrins as well as nitrotyrosine. Immunohistochemistry revealed enhanced local expression of heme oxygenase-1, biopyrrins and nitrotyrosine in allografts in accordance with the cellular infiltrates, suggesting that changes in urinary biopyrrins reflect the bilirubin oxidation in grafts undergoing rejection. These results indicate that locally evoked bilirubin oxidation by NO radicals can predict the progression of rejection.