Abstract
The physiological wound healing process involves a cascade of events which could be affected by several factors resulting in chronic, non-healing wounds. The latter represent a great burden especially when bacterial biofilms are formed. The rise in antibiotic resistance amongst infectious microorganisms leads to the need of novel approaches to treat this clinical issue. In this context, the use of advanced biomaterials, which can enhance the physiological expression and secretion of the growth factors involved in the wound healing process, is gaining increasing attention as a robust and appealing alternative approach. Among them, mesoporous glasses are of particular interest due to their excellent textural properties and to the possibility of incorporating and releasing specific therapeutic species, such as metallic ions. One of the most attractive therapeutic ions is copper thanks to its proangiogenic and antibacterial effects. In this contribution, copper containing mesoporous glass nanoparticles were proposed as a multifunctional device to treat chronic wounds. The developed nanoparticles evidenced a very high specific surface area (740 m2/g), uniform pores of 4 nm and an almost total release of the therapeutic ion within 72 h of soaking. The produced nanoparticles were biocompatible and, when tested against Gram positive and Gram negative bacterial species, demonstrated antibacterial activity against both planktonic and biofilm bacteria in 2D cell monolayers, and in a 3D human model of infected skin. Their proangiogenic effect was tested with both the aortic ring and the chick chorioallantoic membrane assays and an increase in endothelial cell outgrowth at a concentration range between 30 and 300 ng/mL was shown. Overall, in this study biocompatible, multifunctional Cu-containing mesoporous glass nanoparticles were successfully produced and demonstrated to exert both antibacterial and proangiogenic effects.
Highlights
The rise in antibiotic resistance (AMR) amongst infectious microorganisms is a current and increasing global threat (Shallcross et al, 2015; O’Neill, 2016)
Copper ions have previously been shown to have a proangiogenic effect (Zhao et al, 2015) and in the present work we extended this proangiogenic study in a simple in vitro assay of angiogenesis, the chick aortic ring assay—where outgrowth of endothelial cells from rings of embryonic aorta gives a measure of the degree to which the candidate material promotes angiogenesis
In a previous work (Bari et al, 2017) we reported the antibacterial activity of the Cu-mesoporous bioactive glasses (MBGs) against S. epidermidis and E. coli as well as S. aureus, and the current results are consistent with the antimicrobial action against both Gram positive and Gram negative species tested previously published
Summary
The rise in antibiotic resistance (AMR) amongst infectious microorganisms is a current and increasing global threat (Shallcross et al, 2015; O’Neill, 2016). Metal ions, such as silver and copper, are one such set of antimicrobials that are currently of interest as they can be combined with functional materials for designing healthcare devices (Gorzelanny et al, 2016; Liu et al, 2016; Ramasamy and Lee, 2016; Sun et al, 2016; Bayramov and Neff, 2017). Toward the development of novel antimicrobial approaches the authors previously established a 3D tissue engineered model of bacterial infected human skin, constructed from a scaffold of decellularised human dermis seeded with human keratinocytes and dermal fibroblasts (MacNeil et al, 2011) which is thermally injured and infected with bacteria (Shepherd et al, 2009). This model has proven useful in the testing of several novel antimicrobials (Bertal et al, 2009; Shepherd et al, 2011; Zheng et al, 2019) and in performing basic infection studies (Bullock et al, 2019)
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