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AntiBiofilm features of Glycolipid-functionalized Silicone Catheters towards Healthcare-associated infections prevention

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Publications

Fighting S. aureus catheter-related infections with sophorolipids: Electing an antiadhesive strategy or a release one?
Publication . Mendes, Rita M.; Francisco, Ana Paula; Carvalho, Filomena A.; Dardouri, Maïssa; Costa, Bruna; Bettencourt, Ana; Costa, Judite; Gonçalves, Lídia; Costa, Fabíola; Ribeiro, Isabel A. C.
Staphylococcus aureus medical devices related-infections, such as blood stream catheter are of major concern. Their prevention is compulsory and strategies, not prone to the development of resistance, to prevent S. aureus biofilms on catheter surfaces (e.g. silicone) are needed. In this work two different approaches using sophorolipids were studied to prevent S. aureus biofilm formation on medical grade silicone: i) an antiadhesive strategy through covalent bond of sophorolipids to the surface; ii) and a release strategy using isolated most active sophorolipids. Sophorolipids produced by Starmerella bombicola, were characterized by UHPLC-MS and RMN, purified by automatic flash chromatography and tested for their antimicrobial activity towards S. aureus. Highest antimicrobial activity was observed for C18:0 and C18:1 diacetylated lactonic sophorolipids showing a MIC of 50 μg mL−1. Surface modification with acidic or lactonic sophorolipids when evaluating the anti-adhesive or release strategy, respectively, was confirmed by contact angle, FTIR-ATR and AFM analysis. When using a mixture of acidic sophorolipids covalently bonded to silicone surface as antiadhesive strategy cytocompatible surfaces were obtained and a reduction of 90 % on biofilm formation was observed. Nevertheless, if a release strategy is adopted with purified lactonic sophorolipids a higher effect is achieved. Most promising compound was C18:1 diacateylated lactonic sophorolipid that showed no cellular viability reduction when a concentration of 1.5 mg mL−1 was selected and a reduction on biofilm around 5 log units. Results reinforce the applicability of these antimicrobial biosurfactants on preventing biofilms and disclose that their antimicrobial effect is imperative when comparing to their antiadhesive properties.
3D-printed platform multi-loaded with bioactive, magnetic nanoparticles and an antibiotic for re-growing bone tissue
Publication . Saraiva, Ana S.; Ribeiro, Isabel A. C.; Fernandes, Maria H.; Cerdeira, Ana Cláudia; Vieira, Bruno J.C.; Waerenborgh, João Carlos; Pereira, Laura C.J.; Cláudio, Ricardo; Carmezim, Maria João; Gomes, Pedro; Gonçalves, Lídia; Santos, Catarina F.; Bettencourt, Ana
Polymeric platforms obtained by three-dimensional (3D) printing are becoming increasingly important as multifunctional therapeutic systems for bone treatment applications. In particularly, researchers aim to control bacterial biofilm on these 3D-platforms and enhance re-growing bone tissue, at the same time. This study aimed to fabricate a 3D-printed polylactic acid platform loaded with hydroxyapatite (HA), iron oxide nanoparticles (IONPs) and an antibiotic (minocycline) with tuneable properties and multistimuli response. IONPs were produced by a facile chemical co-precipitation method showing an average diameter between 11 and 15 nm and a superparamagnetic behaviour which was preserved when loaded into the 3D-platforms. The presence of two types of nanoparticles (IONPs and HA) modify the nanomorphological/nanotopographical feature of the 3D-platforms justifying their adequate bioactivity profile and in vitro cellular effects on immortalized and primary osteoblasts, including cytocompatibility and increased osteogenesis-related gene expression (RUNX2, BGLAP and SPP1). Disk diffusion assays and SEM analysis confirmed the effect of the 3D-platforms loaded with minocycline against Staphylococcus aureus. Altogether results showed that fabricated 3D-platforms combined the exact therapeutic antibiofilm dose of the antibiotic against S. aureus, with the enhanced osteogenic stimulation of the HA and IONPs nanoparticles which is a disruptive approach for bone targeting applications.
Bonding antimicrobial rhamnolipids onto medical grade PDMS: A strategy to overcome multispecies vascular catheter-related infections
Publication . Dardouri, Maïssa; Aljnadi, Israa M.; Deuermeier, Jonas; Santos, Catarina; Costa, Fabiola; Martin, Victor; Fernandes, Maria H.; Gonçalves, Lídia; Bettencourt, Ana; Gomes, Pedro Sousa; Ribeiro, Isabel A. C.
In clinic there is a demand to solve the drawback of medical devices multispecies related infections. Consequently, different biomaterial surfaces, such as vascular catheters, urgently need improvement regarding their antifouling/antimicrobial properties. In this work, we covalently functionalized medical grade polydimethylsiloxane (PDMS) with antimicrobial rhamnolipids to investigate the biomaterial surface activity towards mono and dual species biofilms. Preparation of surfaces with “piranha” oxidation, followed by APTES bonding and carbodiimide reaction with rhamnolipids effectively bonded these compounds to PDMS surface as confirmed by FTIR-ATR and XPS analysis. Generated surfaces were active towards S. aureus biofilm formation showing a 4.2 log reduction while with S. epidermidis and C. albicans biofilms a reduction of 1.2 and 1.0 log reduction, respectively, was observed. Regarding dual-species testing the higher biofilm log reduction observed was 1.9. Additionally, biocompatibility was assessed by cytocompatibility towards human fibroblastic cells, low platelet activation and absence of vascular irritation. Our work not only sheds light on using covalently bonded rhamnolipids towards dual species biofilms but also highlights the biocompatibility of the obtained PDMS surfaces.

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Funding agency

Fundação para a Ciência e a Tecnologia

Funding programme

3599-PPCDT

Funding Award Number

PTDC/BTM-SAL/29335/2017

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