Amphotericin B-loaded natural latex dressing for treating Candida albicans wound infections using Galleria mellonella model.

Amphotericin B (AmB) is the gold standard for antifungal drugs. However, AmB systemic administration is restricted because of its side effects. Here, we report AmB loaded in natural rubber latex (NRL), a sustained delivery system with low toxicity, which stimulates angiogenesis, cell adhesion and accelerates wound healing. Physicochemical characterizations showed that AmB did not bind chemically to the polymeric matrix. Electronic and topographical images showed small crystalline aggregates from AmB crystals on the polymer surface. About 56.6% of AmB was released by the NRL in 120 h. However, 33.6% of this antifungal was delivered in the first 24 h due to the presence of AmB on the polymer surface. The biomaterial's excellent hemo- and cytocompatibility with erythrocytes and human dermal fibroblasts (HDF) confirmed its safety for dermal wound application. Antifungal assay against Candida albicans showed that AmB-NRL presented a dose-dependent behavior with an inhibition halo of 30.0 ± 1.0 mm. Galleria mellonella was employed as an in vivo model for C. albicans infection. Survival rates of 60% were observed following the injection of AmB (0.5 mg.mL-1) in G. mellonella larvae infected by C. albicans. Likewise, AmB-NRL (0.5 mg.mL-1) presented survival rates of 40%, inferring antifungal activity against fungus. Thus, NRL adequately acts as an AmB-sustained release matrix, which is an exciting approach, since this antifungal is toxic at high concentrations. Our findings suggest that AmB-NRL is an efficient, safe, and reasonably priced ($0.15) dressing for the treatment of cutaneous fungal infections.

Precision-porous polyurethane elastomers engineered for application in pro-healing vascular grafts: Synthesis, fabrication and detailed biocompatibility assessment.

Unmet needs for small diameter, non-biologic vascular grafts and the less-than-ideal performance of medium diameter grafts suggest opportunities for major improvements. Biomaterials that are mechanically matched to native blood vessels, reduce the foreign body capsule (FBC) and demonstrate improved integration and healing are expected to improve graft performance. In this study, we developed biostable, crosslinked polyurethane formulations and used them to fabricate scaffolds with precision-engineered 40 µm pores. We matched the scaffold mechanical properties with those of native blood vessels by optimizing the polyurethane compositions. We hypothesized that such scaffolds promote healing and mitigate the FBC. To test our hypothesis, polyurethanes with 40 µm pores, 100 µm pores, and non-porous slabs were implanted subcutaneously in mice for 3 weeks, and then were examined histologically. Our results show that 40 µm porous scaffolds elicit the highest level of angiogenesis, cellularization, and the least severe foreign body capsule (based on a refined assessment method). This study presents the first biomaterial with tuned mechanical properties and a precision engineered porous structure optimized for healing, thus can be ideal for pro-healing vascular grafts and in situ vascular engineering. In addition, these scaffolds may have wide applications in tissue engineering, drug delivery, and implantable device.

Plasma Polymerized HMDSO Coatings For Syringes To Minimize Protein Adsorption.

Current parenteral containers used for the storage and delivery of protein-based drugs, contain silicone oil which may seep into the protein solution and can result in adsorption, aggregation and denaturation of the protein. Tightly adherent surface coatings prepared by radio frequency glow-discharge (RFGD) plasma polymerization are described in this paper. Using this robust technique, methacrylic acid (MA) (hydrophilic), hexamethyldisiloxane (HMDSO) (hydrophobic), tetraglyme (TG) (hydrophilic) were plasma polymerized onto glass. In addition, HMDSO and MA were copolymerized to create a plasma polymerized HMDSO-MA (hydrophobic) surface. Untreated glass and glass dip-coated in PDMS were used as controls. TG and MA plasma coatings adsorbed the least amount of protein in all pH conditions. Interestingly HMDSO-MA retained significantly lesser protein compared to HMDSO and dip-coated PDMS samples. In the presence of Polysorbate 80 (PS80) all plasma polymerized coatings adsorbed and retained negligible amounts of protein, compared to controls. Furthermore, the peak glide force of plasma coated syringes did not significantly increase compared to syringes without plasma coating. Due to the versatility of RFGD plasma, this process is scalable and could potentially be used for the treatment of hypodermic syringes used for the storage and delivery of protein-based therapeutics.

Highly-reactive haloester surface initiators for ARGET ATRP readily prepared by radio frequency glow discharge plasma.

New surface initiators for ARGET ATRP (activators regenerated by electron transfer atomic transfer radical polymerization) have been prepared by the plasma deposition of haloester monomers. Specifically, methyl 3-bromopropionate (M3BP), methyl 2-chloropropionate, and ethyl 2-fluoropropionate (E2FP) were plasma deposited onto glass discs using RF glow discharge plasma. This technique creates surface coatings that are resistant to delamination and rich in halogen species making them good candidates for surface initiators for ARGET ATRP. Of all the plasma polymerized surface coatings, M3BP showed the highest halogen content and was able to grow 2-hydroxyethyl methacrylate (HEMA) polymer brushes on its surface via ARGET ATRP in as little as 15 min as confirmed by XPS. Surprisingly, E2FP, a fluoroester, was also able to grow HEMA polymer brushes despite fluorine being a poor leaving group for ARGET ATRP. The versatility of RF glow discharge plasma offers a clear advantage over other techniques previously used to immobilize ARGET ATRP surface initiators.

Effect of molecular weight of chitosan degraded by microwave irradiation on lyophilized scaffold for bone tissue engineering applications.

Chitosan (CTS) is biocompatible, biodegradable, and can be formed into 3D porous structures for bone tissue engineering applications. Although studies have reported on the effects of molecular weight (MW) on CTS physicochemical properties, studies evaluating CTS biological property relationships often do not account for MW that confounds interpretation of study results. The aim of this study was to evaluate the effect of MW on CTS physicochemical and biological properties. CTS materials were treated for 6, 18, and 30 min by microwave irradiation to decrease MW without affecting deacetylation (DDA). Materials were evaluated for crystallinity using X-ray diffraction, thermal degradation using differential scanning calorimetry, water content, swelling ratio, and in vitro compatibility using Saos-2. Results showed that microwave treatments did not affect DDA but decreased MW and swelling ratio by 45.78% and 36.75%, respectively, after 30 min of microwave treatment. Microwave-treated CTS showed reduced or no crystalline peaks. Initial increase in exothermic peak temperatures with short (6 min) microwave treatment times were followed by a decrease with longer (18 and 30 min) treatment times. Cell growth over 7 days on samples was proportional to MW with the number of cells being 62% higher on CTS with the highest MW (3.71 ± 0.25 × 10(5) g/mol) when compared with the lower MW CTS (2.38 ± 0.12 × 10(5) g/mol). These results demonstrate the importance of MW of CTS to both its physicochemical characteristics and biological properties, providing researchers with another tool for the modulation and optimization of CTS for different biomedical applications.