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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Infectious Diseases".

Deadline for manuscript submissions: closed (5 November 2019) | Viewed by 66583

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Special Issue Editors

Prof. Dr. Natália Cruz-Martins

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Guest Editor

1. Faculty of Medicine, University of Porto, 4099-002 Porto, Portugal
2. Institute for Research and Inovation in Health (i3S), University of Porto, 4099-002 Porto, Portugal
Interests: evidence-based medicine; phytochemistry; phytopharmacology; drug discovery; natural products biochemistry; bioactive molecules; functional foods; nutraceuticals; fungal and bacterial infections; resistance to antimicrobials
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Dr. Célia Fortuna Rodrigues

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Guest Editor

1. Associate Laboratory i4HB—Institute for Health and Bioeconomy, University Institute of Health Sciences—CESPU, 4585-116 Gandra, Portugal
2. ALiCE—Associate Laboratory in Chemical Engineering, Faculty of Engineering, LEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Porto, Portugal
Interests: biofilms; Candida; AMR; fungal infection; polymicrobial biofilms; alternatives to antifungals
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The use of medical devices (e.g., catheters, implants, and probes) is a common and essential part of medical care for both diagnostic and therapeutic purposes. However, these devices quite frequently lead to the incidence of infections, due to the colonization of their abiotic surfaces by biofilm‐growing microorganisms, which are progressively resistant to antimicrobial therapies. Several methods have been developed to combat device‐related infections, based on anti‐infective biomaterials that repel microbes. Among these strategies, surface coating with antibiotics (e.g., beta-lactams), natural compounds (e.g., polyphenols), or inorganic elements (e.g., silver and copper nanoparticles) have been widely recognized as exhibiting broad-spectrum bactericidal or bacteriostatic activity. So, in order to achieve a better therapeutic response, it is crucial to understand how these infections are different from others to find new biomaterials, characterized by antifouling coatings, with repellent properties or low adhesion towards microorganisms, or antimicrobial coatings, which are capable of killing microbes, approaching the surface, improving biomaterials’ functionalization strategies, and supporting tissues’ bio-integration.

We welcome you to join us in this effort. Review and original research articles are welcome. We look forward to receiving your contributions.

Prof. Dr. Natália Martins
Dr. Célia F. Rodrigues
Guest Editors

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Keywords

Surface coating
Resistant pathogens
Biofilm
Antimicrobial
Drug delivery
Antifouling coating
Natural compound
Device-related infection
Inorganic element

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Published Papers (9 papers)

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Editorial

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3 pages, 183 KiB

Open AccessEditorial

Biomaterial-Related Infections

by Natália Martins and Célia F. Rodrigues

J. Clin. Med. 2020, 9(3), 722; https://doi.org/10.3390/jcm9030722 - 7 Mar 2020

Cited by 22 | Viewed by 2738

Abstract

Medical devices are a typical and important part of health care for both diagnostic and therapeutic purposes [...] Full article

(This article belongs to the Special Issue Biomaterial-Related Infections)

Research

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29 pages, 14365 KiB

Open AccessArticle

Comprehensive Evaluation of the Biological Properties of Surface-Modified Titanium Alloy Implants

by Piotr Piszczek, Aleksandra Radtke, Michalina Ehlert, Tomasz Jędrzejewski, Alicja Sznarkowska, Beata Sadowska, Michał Bartmański, Yaşar Kemal Erdoğan, Batur Ercan and Waldemar Jedrzejczyk

J. Clin. Med. 2020, 9(2), 342; https://doi.org/10.3390/jcm9020342 - 25 Jan 2020

Cited by 31 | Viewed by 5117

Abstract

An increasing interest in the fabrication of implants made of titanium and its alloys results from their capacity to be integrated into the bone system. This integration is facilitated by different modifications of the implant surface. Here, we assessed the bioactivity of amorphous titania nanoporous and nanotubular coatings (TNTs), produced by electrochemical oxidation of Ti6Al4V orthopedic implants’ surface. The chemical composition and microstructure of TNT layers was analyzed by X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). To increase their antimicrobial activity, TNT coatings were enriched with silver nanoparticles (AgNPs) with the chemical vapor deposition (CVD) method and tested against various bacterial and fungal strains for their ability to form a biofilm. The biointegrity and anti-inflammatory properties of these layers were assessed with the use of fibroblast, osteoblast, and macrophage cell lines. To assess and exclude potential genotoxicity issues of the fabricated systems, a mutation reversal test was performed (Ames Assay MPF, OECD TG 471), showing that none of the TNT coatings released mutagenic substances in long-term incubation experiments. The thorough analysis performed in this study indicates that the TNT5 and TNT5/AgNPs coatings (TNT5—the layer obtained upon applying a 5 V potential) present the most suitable physicochemical and biological properties for their potential use in the fabrication of implants for orthopedics. For this reason, their mechanical properties were measured to obtain full system characteristics. Full article

(This article belongs to the Special Issue Biomaterial-Related Infections)

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17 pages, 7556 KiB

Open AccessArticle

Parameters Affecting the Antimicrobial Properties of Cold Atmospheric Plasma Jet

by Bih-Show Lou, Chih-Ho Lai, Teng-Ping Chu, Jang-Hsing Hsieh, Chun-Ming Chen, Yu-Ming Su, Chun-Wei Hou, Pang-Yun Chou and Jyh-Wei Lee

J. Clin. Med. 2019, 8(11), 1930; https://doi.org/10.3390/jcm8111930 - 9 Nov 2019

Cited by 23 | Viewed by 4490

Abstract

Using the Taguchi method to narrow experimental parameters, the antimicrobial efficiency of a cold atmospheric plasma jet (CAPJ) treatment was investigated. An L9 array with four parameters of CAPJ treatments, including the application voltage, CAPJ-sample distance, argon (Ar) gas flow rate, and CAPJ treatment time, were applied to examine the antimicrobial activity against Escherichia coli (E. coli). CAPJ treatment time was found to be the most influential parameter in its antimicrobial ability by evaluation of signal to noise ratios and analysis of variance. 100% bactericidal activity was achieved under the optimal bactericidal activity parameters including the application voltage of 8.5 kV, CAPJ-sample distance of 10 mm, Ar gas flow rate of 500 sccm, and CAPJ treatment time of 300 s, which confirms the efficacy of the Taguchi method in this design. In terms of the mechanism of CAPJ’s antimicrobial ability, the intensity of hydroxyl radical produced by CAPJ positively correlated to its antimicrobial efficiency. The CAPJ antimicrobial efficiency was further evaluated by both DNA double-strand breaks analysis and scanning electron microscopy examination of CAPJ treated bacteria. CAPJ destroyed the cell wall of E. coli and further damaged its DNA structure, thus leading to successful killing of bacteria. This study suggests that optimal conditions of CPAJ can provide effective antimicrobial activity and may be grounds for a novel approach for eradicating bacterial infections. Full article

(This article belongs to the Special Issue Biomaterial-Related Infections)

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21 pages, 10477 KiB

Open AccessArticle

Electrospun Polyethylene Terephthalate Nanofibers Loaded with Silver Nanoparticles: Novel Approach in Anti-Infective Therapy

by Alexandru Mihai Grumezescu, Alexandra Elena Stoica, Mihnea-Ștefan Dima-Bălcescu, Cristina Chircov, Sami Gharbia, Cornel Baltă, Marcel Roșu, Hildegard Herman, Alina Maria Holban, Anton Ficai, Bogdan Stefan Vasile, Ecaterina Andronescu, Mariana Carmen Chifiriuc and Anca Hermenean

J. Clin. Med. 2019, 8(7), 1039; https://doi.org/10.3390/jcm8071039 - 16 Jul 2019

Cited by 39 | Viewed by 4996

Abstract

Polyethylene terephthalate (PET) is a major pollutant polymer, due to its wide use in food packaging and fiber production industries worldwide. Currently, there is great interest for recycling the huge amount of PET-based materials, derived especially from the food and textile industries. In this study, we applied the electrospinning technique to obtain nanostructured fibrillary membranes based on PET materials. Subsequently, the recycled PET networks were decorated with silver nanoparticles through the chemical reduction method for antimicrobial applications. After the characterization of the materials in terms of crystallinity, chemical bonding, and morphology, the effect against Gram-positive and Gram-negative bacteria, as well as fungal strains, was investigated. Furthermore, in vitro and in vivo biocompatibility tests were performed in order to open up potential biomedical applications, such as wound dressings or implant coatings. Silver-decorated fibers showed lower cytotoxicity and inflammatory effects and increased antibiofilm activity, thus highlighting the potential of these systems for antimicrobial purposes. Full article

(This article belongs to the Special Issue Biomaterial-Related Infections)

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23 pages, 5699 KiB

Open AccessArticle

“To Be Microbiocidal and Not to Be Cytotoxic at the Same Time…”—Silver Nanoparticles and Their Main Role on the Surface of Titanium Alloy Implants

by Aleksandra Radtke, Marlena Grodzicka, Michalina Ehlert, Tomasz Jędrzejewski, Magdalena Wypij and Patrycja Golińska

J. Clin. Med. 2019, 8(3), 334; https://doi.org/10.3390/jcm8030334 - 10 Mar 2019

Cited by 29 | Viewed by 3970

Abstract

The chemical vapor deposition (CVD) method has been used to produce dispersed silver nanoparticles (AgNPs) on the surface of titanium alloy (Ti6Al4V) and nanotubular modified titanium alloys (Ti6Al4V/TNT5), leading to the formation of Ti6Al4V/AgNPs and Ti6Al4V/TNT5/AgNPs systems with different contents of metallic silver particles. Their surface morphology and silver particles arrangement were characterized by scanning electron microscopy (SEM), energy dispersive X-ray spectrometry (EDS), and atomic force microscopy (AFM). The wettability and surface free energy of these materials were investigated on the basis of contact angle measurements. The degree of silver ion release from the surface of the studied systems immersed in phosphate buffered saline solution (PBS) was estimated using inductively coupled plasma ionization mass spectrometry (ICP-MS). The biocompatibility of the analyzed materials was estimated based on the fibroblasts and osteoblasts adhesion and proliferation, while their microbiocidal properties were determined against Gram-positive and Gram-negative bacteria, and yeasts. The results of our works proved the high antimicrobial activity and biocompatibility of all the studied systems. Among them, Ti6Al4V/TNT5/0.6AgNPs contained the lowest amount of AgNPs, but still revealed optimal biointegration properties and high biocidal properties. This is the biomaterial that possesses the desired biological properties, in which the potential toxicity is minimized by minimizing the number of silver nanoparticles. Full article

(This article belongs to the Special Issue Biomaterial-Related Infections)

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22 pages, 5620 KiB

Open AccessArticle

The Morphology, Structure, Mechanical Properties and Biocompatibility of Nanotubular Titania Coatings before and after Autoclaving Process

by Aleksandra Radtke, Michalina Ehlert, Tomasz Jędrzejewski and Michał Bartmański

J. Clin. Med. 2019, 8(2), 272; https://doi.org/10.3390/jcm8020272 - 23 Feb 2019

Cited by 19 | Viewed by 3977

Abstract

The autoclaving process is one of the sterilization procedures of implantable devices. Therefore, it is important to assess the impact of hot steam at high pressure on the morphology, structure, and properties of implants modified by nanocomposite coatings. In our works, we focused on studies on amorphous titania nanotubes produced by titanium alloy (Ti6Al4V) electrochemical oxidation in the potential range 5–60 V. Half of the samples were drying in argon stream at room temperature, and the second ones were drying additionally with the use of immersion in acetone and drying at 396 K. Samples were subjected to autoclaving and after sterilization they were structurally and morphologically characterized using Raman spectroscopy, diffuse reflectance infrared Fourier transform spectroscopy (DRIFT) and scanning electron microscopy (SEM). They were characterized in terms of wettability, mechanical properties, and biocompatibility. Obtained results proved that the autoclaving of amorphous titania nanotube coatings produced at lower potentials (5–15 V) does not affect their morphology and structure regardless of the drying method before autoclaving. Nanotubular coatings produced using higher potentials (20–60 V) require removal of adsorbed water particles from their surface. Otherwise, autoclaving leads to the destruction of the architecture of nanotubular coatings, which is associated with the changing of their mechanical and biointegration properties. Full article

(This article belongs to the Special Issue Biomaterial-Related Infections)

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16 pages, 5686 KiB

Open AccessArticle

Inflammatory Cell Recruitment in Candida glabrata Biofilm Cell-Infected Mice Receiving Antifungal Chemotherapy

by Célia F. Rodrigues, Alexandra Correia, Manuel Vilanova and Mariana Henriques

J. Clin. Med. 2019, 8(2), 142; https://doi.org/10.3390/jcm8020142 - 26 Jan 2019

Cited by 12 | Viewed by 3785

Abstract

(1) Background: Due to a high rate of antifungal resistance, Candida glabrata is one of the most prevalent Candida spp. linked to systemic candidiasis, which is particularly critical in catheterized patients. The goal of this work was to simulate a systemic infection exclusively derived from C. glabrata biofilm cells and to evaluate the effectiveness of the treatment of two echinocandins—caspofungin (Csf) and micafungin (Mcf). (2) Methods: CD1 mice were infected with 48 h-biofilm cells of C. glabrata and then treated with Csf or Mcf. After 72 h, the efficacy of each drug was evaluated to assess the organ fungal burden through colony forming units (CFU) counting. The immune cell recruitment into target organs was evaluated by flow cytometry or histopathology analysis. (3) Results: Fungal burden was found to be higher in the liver than in the kidneys. However, none of the drugs was effective in completely eradicating C. glabrata biofilm cells. At the evaluated time point, flow cytometry analysis showed a predominant mononuclear response in the spleen, which was also evident in the liver and kidneys of the infected mice, as observed by histopathology analysis. (4) Conclusions: Echinocandins do not have a significant impact on liver and kidney fungal burden, or recruited inflammatory infiltrate, when mice are intravenously (i.v.) infected with C. glabrata biofilm-grown cells. Full article

(This article belongs to the Special Issue Biomaterial-Related Infections)

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Review

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16 pages, 353 KiB

Open AccessReview

Management of Streptococcus mutans-Candida spp. Oral Biofilms’ Infections: Paving the Way for Effective Clinical Interventions

by Bahare Salehi, Dorota Kregiel, Gail Mahady, Javad Sharifi-Rad, Natália Martins and Célia F. Rodrigues

J. Clin. Med. 2020, 9(2), 517; https://doi.org/10.3390/jcm9020517 - 14 Feb 2020

Cited by 28 | Viewed by 8724

Abstract

Oral diseases are considered the most common noncommunicable diseases and are related to serious local and systemic disorders. Oral pathogens can grow and spread in the oral mucosae and frequently in biomaterials (e.g., dentures or prostheses) under polymicrobial biofilms, leading to several disorders such as dental caries and periodontal disease. Biofilms harbor a complex array of interacting microbes, increasingly unapproachable to antimicrobials and with dynamic processes key to disease pathogenicity, which partially explain the gradual loss of response towards conventional therapeutic regimens. New drugs (synthesized and natural) and other therapies that have revealed promising results for the treatment or control of these mixed biofilms are presented and discussed here. A structured search of bibliographic databases was applied to include recent research. There are several promising new approaches in the treatment of Candida spp.–Streptococcus mutans oral mixed biofilms that could be clinically applied in the near future. These findings confirm the importance of developing effective therapies for oral Candida–bacterial infections. Full article

(This article belongs to the Special Issue Biomaterial-Related Infections)

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41 pages, 1571 KiB

Open AccessReview

Candida sp. Infections in Patients with Diabetes Mellitus

by Célia F. Rodrigues, Maria Elisa Rodrigues and Mariana Henriques

J. Clin. Med. 2019, 8(1), 76; https://doi.org/10.3390/jcm8010076 - 10 Jan 2019

Cited by 158 | Viewed by 27730

Abstract

Candidiasis has increased substantially worldwide over recent decades and is a significant cause of morbidity and mortality, especially among critically ill patients. Diabetes mellitus (DM) is a metabolic disorder that predisposes individuals to fungal infections, including those related to Candida sp., due to a immunosuppressive effect on the patient. This review aims to discuss the latest studies regarding the occurrence of candidiasis on DM patients and the pathophysiology and etiology associated with these co-morbidities. A comprehensive review of the literature was undertaken. PubMed, Scopus, Elsevier’s ScienceDirect, and Springer’s SpringerLink databases were searched using well-defined search terms. Predefined inclusion and exclusion criteria were applied to classify relevant manuscripts. Results of the review show that DM patients have an increased susceptibility to Candida sp. infections which aggravates in the cases of uncontrolled hyperglycemia. The conclusion is that, for these patients, the hospitalization periods have increased and are commonly associated with the prolonged use of indwelling medical devices, which also increase the costs associated with disease management. Full article

(This article belongs to the Special Issue Biomaterial-Related Infections)

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