Emerging Strategies to Prevent Bacterial Infections on Titanium-Based Implants.

Titanium and titanium alloys remain the gold standard for dental and orthopedic implants. These materials are heavily used because of their bioinert nature, robust mechanical properties, and seamless integration with bone. However, implant-associated infections (IAIs) remain one of the leading causes of implant failure. Eradicating an IAI can be difficult since bacteria can form biofilms on the medical implant, protecting the bacterial cells against systemic antibiotics and the host's immune system. If the infection is not treated promptly and aggressively, device failure is inevitable, leading to costly multi-step revision surgeries. To circumvent this dire situation, scientists and engineers continue to develop novel strategies to protect the surface of medical implants from bacteria. In this review, details on emerging strategies to prevent infection in titanium implants are reported. These strategies include anti-adhesion properties provided by polymers, superhydrophobic, superhydrophilic, and liquid-infused surface coatings, as well as strategies and coatings employed to lyse the bacteria. Additionally, commercially available technologies and those under preclinical trials are examined while discussing current and future trends.

An Omniphobic Spray Coating Created from Hierarchical Structures Prevents the Contamination of High-Touch Surfaces with Pathogens.

Engineered surfaces that repel pathogens are of great interest due to their role in mitigating the spread of infectious diseases. A robust, universal, and scalable omniphobic spray coating with excellent repellency against water, oil, and pathogens is presented. The coating is substrate-independent and relies on hierarchically structured polydimethylsiloxane (PDMS) microparticles, decorated with gold nanoparticles (AuNPs). Wettability studies reveal the relationship between surface texturing of micro- and/or nano-hierarchical structures and the omniphobicity of the coating. Studies of pathogen transfer with bacteria and viruses reveal that an uncoated contaminated glove transfers pathogens to >50 subsequent surfaces, while a coated glove picks up 104 (over 99.99%) less pathogens upon first contact and transfers zero pathogens after the second touch. The developed coating also provides excellent stability under harsh conditions. The remarkable anti-pathogen properties of this surface combined with its ease of implementation, substantiate its use for the prevention of surface-mediated transmission of pathogens.

Oral delivery of posaconazole-loaded phospholipid-based nanoformulation: Preparation and optimization using design of experiments, machine learning, and TOPSIS.

Phospholipid-based nanosystems show promising potentials for oral administration of hydrophobic drugs. The study introduced a novel approach to optimize posaconazole-loaded phospholipid-based nanoformulation using the design of experiments, machine learning, and Technique for Order of Preference by Similarity to the Ideal Solution. These approaches were used to investigate the impact of various variables on the encapsulation efficiency (EE), particle size, and polydispersity index (PDI). The optimized formulation, with %EE of âˆ¼ 74 %, demonstrated a particle size and PDI of 107.7 nm and 0.174, respectively. The oral pharmacokinetic profiles of the posaconazole suspension, empty nanoformulation + drug suspension, and drug-loaded nanoformulation were evaluated. The nanoformulation significantly increased maximum plasma concentration and the area under the drug plasma concentration-time curve (∼3.9- and 6.2-fold, respectively) and could be administered without regard to meals. MTT and histopathological examinations were carried out to evaluate the safety of the nanoformulation and results exhibited no significant toxicity. Lymphatic transport was found to be the main mechanism of oral delivery. Caco-2 cell studies demonstrated that the mechanism of delivery was not based on an increase in cellular uptake. Our study represents a promising strategy for the development of phospholipid-based nanoformulations as efficient and safe oral delivery systems.

High-throughput fabrication of antimicrobial phage microgels and example applications in food decontamination.

Engineered by nature, biological entities are exceptional building blocks for biomaterials. These entities can impart enhanced functionalities on the final material that are otherwise unattainable. However, preserving the bioactive functionalities of these building blocks during the material fabrication process remains a challenge. We describe a high-throughput protocol for the bottom-up self-assembly of highly concentrated phages into microgels while preserving and amplifying their inherent antimicrobial activity and biofunctionality. Each microgel is comprised of half a million cross-linked phages as the sole structural component, self-organized in aligned bundles. We discuss common pitfalls in the preparation procedure and describe optimization processes to ensure the preservation of the biofunctionality of the phage building blocks. This protocol enables the production of an antimicrobial spray containing the manufactured phage microgels, loaded with potent virulent phages that effectively reduced high loads of multidrug-resistant Escherichia coli O157:H7 on red meat and fresh produce. Compared with other microgel preparation methods, our protocol is particularly well suited to biological materials because it is free of organic solvents and heat. Bench-scale preparation of base materials, namely microporous films (the template for casting microgels) and pure concentrated phage suspension, requires 3.5 h and 5 d, respectively. A single production run, that yields over 1,750,000 microgels, ranges from 2 h to 2 d depending on the rate of cross-linking chemistry. We expect that this platform will address bottlenecks associated with shelf-stability, preservation and delivery of phage for antimicrobial applications, expanding the use of phage for prevention and control of bacterial infections and contaminants.

High throughput platform technology for rapid target identification in personalized phage therapy.

As bacteriophages continue to gain regulatory approval for personalized human therapy against antibiotic-resistant infections, there is a need for transformative technologies for rapid target identification through multiple, large, decentralized therapeutic phages biobanks. Here, we design a high throughput phage screening platform comprised of a portable library of individual shelf-stable, ready-to-use phages, in all-inclusive solid tablets. Each tablet encapsulates one phage along with luciferin and luciferase enzyme stabilized in a sugar matrix comprised of pullulan and trehalose capable of directly detecting phage-mediated adenosine triphosphate (ATP) release through ATP bioluminescence reaction upon bacterial cell burst. The tablet composition also enhances desiccation tolerance of all components, which should allow easier and cheaper international transportation of phages and as a result, increased accessibility to therapeutic phages. We demonstrate high throughput screening by identifying target phages for select multidrug-resistant clinical isolates of Pseudomonas aeruginosa, Salmonella enterica, Escherichia coli, and Staphylococcus aureus with targets identified within 30-120 min.

A Bifunctional Spray Coating Reduces Contamination on Surfaces by Repelling and Killing Pathogens.

Surface-mediated transmission of pathogens is a major concern with regard to the spread of infectious diseases. Current pathogen prevention methods on surfaces rely on the use of biocides, which aggravate the emergence of antimicrobial resistance and pose harmful health effects. In response, a bifunctional and substrate-independent spray coating is presented herein. The bifunctional coating relies on wrinkled polydimethylsiloxane microparticles, decorated with biocidal gold nanoparticles to induce a "repel and kill" effect against pathogens. Pathogen repellency is provided by the structural hierarchy of the microparticles and their surface chemistry, whereas the kill mechanism is achieved using functionalized gold nanoparticles embedded on the microparticles. Bacterial tests with methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa reveal a 99.9% reduction in bacterial load on spray-coated surfaces, while antiviral tests with Phi6─a bacterial virus often used as a surrogate to SARS-CoV-2─demonstrate a 98% reduction in virus load on coated surfaces. The newly developed spray coating is versatile, easily applicable to various surfaces, and effective against various pathogens, making it suitable for reducing surface contamination in frequently touched, heavy traffic, and high-risk surfaces.

Highly Stable Hierarchically Structured All-Polymeric Lubricant-Infused Films Prevent Thrombosis and Repel Multidrug-Resistant Pathogens.

Thrombus formation and infections caused by bacterial adhesion are the most common causes of failure in blood-contacting medical devices. Reducing the interaction of pathogens using repellent surfaces has proven to be a successful strategy in preventing device failure. However, designing scale-up methodologies to create large-scale repellent surfaces remains challenging. To address this need, we have created an all-polymeric lubricant-infused system using an industrially viable swelling-coagulation solvent (S-C) method. This induces hierarchically structured micro/nano features onto the surface, enabling improved lubricant infusion. Poly(3,3,3-trifluoropropylmethylsiloxane) (PTFS) was used as the lubricant of choice, a previously unexplored omniphobic nonvolatile silicone oil. This resulted in all-polymeric liquid-infused surfaces that are transparent and flexible with long-term stability. Repellent properties have been demonstrated using human whole blood and methicillin-resistant Staphylococcus aureus (MRSA) bacteria matrices, with lubricated surfaces showing 93% reduction in blood stains and 96.7% reduction in bacterial adherence. The developed material has the potential to prevent blood and pathogenic contamination for a range biomedical devices within healthcare settings.

Algal Cells-Derived Extracellular Vesicles: A Review With Special Emphasis on Their Antimicrobial Effects.

Extracellular vesicles (EVs) originated from different cells of approximately all kinds of organisms, recently got more attention because of their potential in the treatment of diseases and reconstructive medicine. To date, lots of studies have been performed on mammalian-derived vesicles, but little attention has been paid to algae and marine cells as valuable sources of EVs. Proving the promising role of EVs in medicine requires sufficient resources to produce qualified microvesicles. Algae, same as its other sister groups, such as plants, have stem cells and stem cell niches. Previous studies showed the EVs in plants and marine cells. So, this study was set out to talk about algal extracellular vesicles. EVs play a major role in cell-to-cell communication to convey molecules, such as RNA/DNA, metabolites, proteins, and lipids within. The components of EVs depends on the origin of the primitive cells or tissues and the isolation method. Sufficient resources are needed to produce high-quality, stable, and compatible EVs as a drug or drug delivery system. Plant stem cells have great potential as a new controllable resource for the production of EVs. The EVs secreted from stem cells can easily be extracted from the cell culture medium and evaluated for medicinal uses. In this review, the aim is to introduce algae stem cells as well as EVs derived from algal cells. In the following, the production of the EVs¸ the properties of EVs extracted from these sources and their antimicrobial effects will be discussed.

Regenerating heavily biofouled dissolved oxygen sensors using bacterial viruses.

Bacterial biofilms are aggregates of bacterial cells embedded in a self-produced extracellular polymeric matrix. Biofilm formation has always been considered a major challenge for sensors used in underwater measurements, and is a primary source of measurement error, especially when it comes to long-term in situ monitoring. We demonstrate the utility of lytic bacteriophages (bacterial viruses) as a non-invasive strategy for removing bacterial biofilms formed on the gas permeable membrane of electrochemical dissolved oxygen sensors. Our results show that a 4 day Pseudomonas aeruginosa biofilm with a fully developed matrix significantly affected the sensor signal and response time, decreasing the signal by 32% and increasing the response time by 94%. In addition, measurements with the biofouled membrane had a very low signal to nose ratio compared to a clean sensor membrane. A single dose of overnight phage treatment effectively removed the biofilm (as indicated by scanning electron micrographs and fluorescence images of the membrane), without the need for repeated treatments. Furthermore, the sensor signal that had plummeted by 32% for a fully biofouled membrane, was returned to the original value (7.96 ± 0.27 mg L-1) after phage treatment and the signal to noise ratio (calculated as the ratio of mean to standard deviation) increased 8 folds for a phage-treated membrane compared to a biofouled membrane. Our data indicate near complete regeneration and signal recovery for the dissolved oxygen sensor, making the biofouled sensor reusable without the use of harsh chemicals that could destroy the fragile sensor membrane.

Single and multi-functional coating strategies for enhancing the biocompatibility and tissue integration of blood-contacting medical implants.

Device-associated clot formation and poor tissue integration are ongoing problems with permanent and temporary implantable medical devices. These complications lead to increased rates of mortality and morbidity and impose a burden on healthcare systems. In this review, we outline the current approaches for developing single and multi-functional surface coating techniques that aim to circumvent the limitations associated with existing blood-contacting medical devices. We focus on surface coatings that possess dual hemocompatibility and biofunctionality features and discuss their advantages and shortcomings to providing a biocompatible and biodynamic interface between the medical implant and blood. Lastly, we outline the newly developed surface modification techniques that use lubricant-infused coatings and discuss their unique potential and limitations in mitigating medical device-associated complications.

Potential application of liposomal nanodevices for non-cancer diseases: an update on design, characterization and biopharmaceutical evaluation.

Liposomes, lipid-based vesicular systems, have attracted major interest as a means to improve drug delivery to various organs and tissues in the human body. Recent literature highlights the benefits of liposomes for use as drug delivery systems, including encapsulating of both hydrophobic and hydrophilic cargos, passive and active targeting, enhanced drug bioavailability and therapeutic effects, reduced systemic side effects, improved cargo penetration into the target tissue and triggered contents release. Pioneering work of liposomes researchers led to introduction of long-circulating, ligand-targeted and triggered release liposomes, as well as, liposomes containing nucleic acids and vesicles containing combination of cargos. Altogether, these findings have led to widespread application of liposomes in a plethora of areas from cancer to conditions such as cardiovascular, neurologic, respiratory, skin, autoimmune and eye disorders. There are numerous review articles on the application of liposomes in treatment of cancer, which seems the primary focus, whereas other diseases also benefit from liposome-mediated treatments. Therefore, this article provides an illustrated detailed overview of liposomal formulations, in vitro characterization and their applications in different disorders other than cancer. Challenges and future directions, which must be considered to obtain the most benefit from applications of liposomes in these disorders, are discussed.

Nanomedicine approaches for sirolimus delivery: a review of pharmaceutical properties and preclinical studies.

Sirolimus (rapamycin) is a mammalian target of rapamycin (mTOR) inhibitor with immunosuppressive, antiproliferative, antiangiogenic, antifungal, anti-restenosis and anti-inflammatory properties. However, its clinical application is often hampered by poor aqueous solubility, first-pass metabolism, transport by p-glycoprotein efflux pump, limited oral bioavailability and nonspecific distribution in off-target sites. Recently, various formulation strategies have emerged to overcome these limitations. Among these, pharmaceutical nanotechnology with numerous advantages has great potential for sirolimus delivery. Up to now, the only nanoparticle based FDA approved formulation in the market is Rapamune® tablet which is composed of drug nanocrystals. This review focuses on recent studies that have been investigated various nanostructured carriers such as liposomes, micelles, polymeric nanoparticles, nanocrystals, magnetic nanoparticles, albumin nanoparticles, solid dispersion nanoparticles and niosomes for sirolimus delivery (in organ transplantation, cancer, vascular restenosis, etc.).