LL37-capped silver nanoparticles have antibacterial properties including inhibition of Pseudomonas aeruginosa biofilm formation, but do not affect human skin fibroblast proliferation.

The increasing number of multidrug resistant bacteria has revitalized interest in seeking alternative sources for controlling bacterial infection. Silver nanoparticles (AgNPs), are amongst the most promising candidates due to their wide microbial spectrum of action. In this work, we report on the safety and efficacy of the incorporation of collagen coated AgNPs into collagen hydrogels for tissue engineering.The resulting hybrid materials at [AgNPs] < 0.4 µM retained the mechanical properties and biocompatibility for primary human skin fibroblasts and keratinocytes of collagen hydrogels; they also displayed remarkable anti-infective properties against S. aureus, S. epidermidis, E. coli and P. aeruginosa at considerably lower concentrations than silver nitrate. Further, subcutaneous implants of materials containing 0.2 µM AgNPs in mice showed a reduction in the levels of IL-6 and other inflammation markers (CCL24, sTNFR-2, and TIMP1). Finally, an analysis of silver contents in implanted mice showed that silver accumulation primarily occurred within the tissue surrounding the implant. IntroductionBiomaterial-associated infections are a significant healthcare problem and have been linked to medical morbidity and death. [2][3][4][5][6] This has motivated the development of materials with anti-infective properties, such as biomaterials loaded with antibiotics. 7 However, with the increasing number of bacteria that are resistant to antibiotics, 8 silver with historically documented anti-microbial activity has re-gained its attractiveness as an alternative to antibiotics. 9 While toxic to bacteria, it unfortunately is also toxic to mammalian cells. 9,10 More recently, therefore, silver nanoparticles (AgNPs) have been evaluated as a safer alternative to ionic silver. 1,[11][12][13][14][15][16][17][18][19][20] The recent work from our team showed that in comparison with silver, biomolecule-coated, photochemically-produced AgNPs can have both bactericidal and bacteriostatic properties with almost negligible cytotoxic effects. 12 We also showed that oxidation of Ag to AgO is most likely the cause of the cytotoxic effects observed with AgNPs. Our overarching goal is to expand the safe use of AgNPs in the development of implantable hybrid-biomaterials with antiinfective properties for future use as scaffolds to enable regeneration of tissue and organs at a risk of bacterial colonization and concomitant biofilm formation like diabetic foot ulcers. Although some collagen-based materials including † Electronic supplementary information (ESI) available: Representative absorption spectra of AgNP@collagen nanoparticles before and after lyophilization. Absorption spectra for the washes obtained from a 1.0 µM AgNP hydrogel over the course of 5 days. Area under the curve (AUC) calculated from the absorption spectra of 500 µm thickness collagen hydrogels prepared using different concentrations of AgNP@collagen. Selected Cryo-SEM images of BDDGE type I collagen-based hydrogels in the absence or presence of 1.0 µM AgNP. An image of a sel...

The role of recombinant Type-I human collagen in the free form or forming AgNP@collagen on the photophysical and photochemical behavior of rose Bengal was analyzed. The formation of dye aggregates on the protein surface was experimentally observed and corroborated by docking calculations. The formation of such aggregates is believed to change the main oxidative mechanism from Type-II (singlet oxygen) to Type-I (free radical) photosensitization. Remarkably, the presence of AgNP in the form of AgNP@collagen altered the dynamics of dye triplet deactivation, effectively preventing the dye degradation and reducing the extent of protein crosslinked. Both crosslinked rHC and AgNP@collagen were able to support fibroblasts proliferation, but only the material containing silver was resistant to S. epidermidis infection.

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Abstract:The anti-peroxyl radical quality of two aqueous rooibos infusions and solutions of their most abundant glycosylated polyphenols was evaluated using pyrogallol red and fluorescein-based oxygen radical absorbance ratios. It was observed that the artificial infusions, prepared using only the most abundant polyphenols present in rooibos and at concentrations similar to those found in the natural infusions, showed greater antioxidant OPEN ACCESSMolecules 2013, 18 11265 quality than the latter infusions, reaching values close to those reported for tea infusions. Additionally, the antimicrobial activity of the natural and artificial infusions was assessed against three species of bacteria: Gram (+) Staphylococcus epidermidis and Staphylococcus aureus and Gram (−) Escherichia coli. When compared to the natural infusions the artificial beverages did not demonstrate any bacterostatic/cidal activity, suggesting that the antibacterial activity of rooibos is related to compounds other than the glycosylated polyphenols employed in our study.

Covalently cross-linked and hydrolytically degradable poly(oligoethylene glycol methacrylate) (POEGMA)based nanogels are fabricated using an all-aqueous self-assembly approach. The nanogels are composed of hydrazide-(POH) and aldehyde-functionalized (POA) POEGMA precursor polymers that exhibit lower critical solution temperature (LCST) behavior in aqueous media and form a covalent, yet degradable, hydrazone linkage upon mixing. By systematically changing the chemistry of the core and cross-linking precursor polymers, the concentration of the core precursor polymer, the ratio of core to cross-linking precursor polymer, and the temperature at which the assembly is conducted, a library of nanogels was produced with significant differences in size, polydispersity, and colloidal stability. Multivariate statistics indicates the presence of significant nonlinear responses within the process variables as well as correlations between the output variables, reflective of the complex balance of aggregation and stabilization mechanisms at play to produce a stable, monodisperse nanogel population. Furthermore, formulations that yield more polydisperse nanogels on a small scale result in macroscopic aggregate formation when scaled up while formulations that yield more monodisperse nanogels can be scaled to yield nanogels with matched properties. We anticipate these results can be applied to strategically synthesize stable, covalently cross-linked, degradable nanogels with targeted sizes at scalable quantities for a range of biomedical and biosensing applications.

While microgels and nanogels are most commonly used for the delivery of hydrophilic therapeutics, the water-swollen structure, size, deformability, colloidal stability, functionality, and physicochemical tunability of microgels can also offer benefits for addressing many of the barriers of conventional vehicles for the delivery of hydrophobic therapeutics. In this review, we describe approaches for designing microgels with the potential to load and subsequently deliver hydrophobic drugs by creating compartmentalized microgels (e.g., core−shell structures), introducing hydrophobic domains in microgels, leveraging host−guest interactions, and/or applying "smart" environmentally responsive materials with switchable hydrophobicity. In particular, the challenge of promoting hydrophobic drug loading without compromising the inherent advantages of microgels as delivery vehicles and ensuring practically relevant release kinetics from such structures is highlighted, with an eye toward the practical translation of such vehicles to the clinic.

Multiresponsive smart materials with the capacity to reversibly change properties (i.e., size, charge) upon the application of more than one stimulus (i.e., temperature, pH) offer potential in numerous biotechnology and biomedical applications. However, their typical lack of degradability limits their potential in vivo use. Herein, we demonstrate the use of an aqueous thermally driven self-assembly approach based on hydrazide- and aldehyde-functionalized poly­(N-isopropylacrylamide) (PNIPAM) oligomers functionalized with pH-ionizable cationic or anionic comonomers for fabricating degradable temperature/pH dual-responsive microgels. The self-assembled microgels show properties analogous to conventional cationic or anionic PNIPAM microgels, retaining their thermal responsiveness while exhibiting pH-driven swelling upon functional comonomer ionization. Amphoteric microgels can also be produced by mixing cationic- and anionic-functionalized precursor polymers during the self-assembly process that reproduce the high-pH/low-pH parabolic swelling response observed in conventional amphoteric microgels. Coupling the precise dual-responsive swelling responses achievable with the degradability of the hydrazone cross-links, self-assembled charged PNIPAM microgels offer potential for improved performance in drug delivery applications requiring dual pH/temperature-specific delivery (e.g. infection sites or cancer).