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...