Bacteria reside within biofilms at the infection site, making them extremely difficult to eradicate with conventional wound care products. Bacteria use quorum sensing (QS) systems to regulate biofilm formation, and QS inhibitors (QSIs) have been proposed as promising antibiofilm agents. Despite this, few antimicrobial therapies that interfere with QS exist. Nontoxic hydroxypropyl‐β‐cyclodextrin‐functionalized cellulose gauzes releasing a burst of the antibiotic vancomycin and the QSI hamamelitannin are developed, followed by a sustained release of both. The gauzes affect QS and biofilm formation of Pseudomonas aeruginosa and Staphylococcus aureus in an in vitro model of chronic wound infection and can be considered as candidates to be used to prevent wound infection as well as treat infected wounds.
Polyelectrolyte block copolymer micelles assembled thin film is switched in response to local photocatalytic reactions on titanium dioxide, resulting in a layer of variable height, stiffness in response to visible light irradiation. Preosteoblasts migrate toward stiffer side of the substrates.
This study aims to develop an effective method to control motile microorganisms and enable their manipulation as functional ‘live micro/nano robots'. A novel strategy based on Fe3O4 nanoparticle‐doped alginate hydrogel is developed to fashion an artificial extracellular matrix (ECM) for microbial cells (e.g., Saccharomyces cerevisiae and Flavobacterium heparinum). During this strategy, a single layer of alginate hydrogel is coated around the microbial cells doped with Fe3O4 nanoparticles to form the alg‐mag‐cells. Transmission electron microscopy shows that Fe3O4 nanoparticles are uniformly distributed in the hydrogel shell. Together with maintaining the cell activity and metabolism, the hydrogel coated microbial cells demonstrate high magnetic responsiveness in an external magnetic field and are able to form micro‐scaled patterns using the magnetic template designed in this study. This strategy provides a building block to fabricate advanced biological models, medical therapeutic products, and non‐medical biological systems using different microorganisms.
The aim of this study is to design a polymeric nanogel system with tailorable degradation behavior. To this end, hydroxyethyl methacrylate‐oligoglycolates‐derivatized poly(hydroxypropyl methacrylamide) (pHPMAm‐Gly‐HEMA) and hydroxyethyl methacrylamide‐oligoglycolates‐derivatized poly(hydroxyethyl methacrylamide) (pHEMAm‐Gly‐HEMAm) are synthesized and characterized. pHEMAm‐Gly‐HEMAm shows faster hydrolysis rates of both carbonate and glycolate esters than the same ester groups of pHPMAm‐Gly‐HEMA. pHEMAm‐Gly‐HEMAm nanogels have tailorable degradation kinetics from 24 h to more than 4 d by varying their crosslink densities. It is shown that the release of a loaded macromolecular model drug is controlled by degradation of nanogels. The nanogels show similar cytocompatibility as PLGA nanoparticles and are therefore considered to be attractive systems for drug delivery.
Polymicrobial biofilm‐associated implant infections present a challenging clinical problem. Through modifications of lyophilized chitosan sponges, degradable drug delivery devices for antibiotic solution have been fabricated for prevention and treatment of contaminated musculoskeletal wounds. Elution of amikacin, vancomycin, or a combination of both follows a burst release pattern with vancomycin released above minimum inhibitory concentration for Staphylococcus aureus for 72 h and amikacin released above inhibitory concentrations for Pseudomonas aeruginosa for 3 h. Delivery of a vancomycin, amikacin, or a combination of both reduces biofilm formation on polytetrafluoroethylene catheters in an in vivo model of contamination. Release of dual antibiotics from sponges is more effective at preventing biofilm formation than single‐loaded chitosan sponges. Treatment of pre‐formed biofilm with high‐dose antibiotic release from chitosan sponges shows minimal reduction after 48 h. These results demonstrate infection‐preventive efficacy for antibiotic‐loaded sponges, as well as the need for modifications in the development of advanced materials to enhance treatment efficacy in removing established biofilm.
A visible light and pH responsive anticancer drug delivery system based on polymer‐coated mesoporous silica nanoparticles (MSNs) has been developed. Perylene‐functionalized poly(dimethylaminoethyl methacrylates) sensitive to visible light and pH are electrostatically attached on the surface of MSNs to seal the nanopores. Stimulation of visible light and acid can unseal the nanopores to induce controlled drug release from the MSNs. More interestingly, the release can be enhanced under the combined stimulation of the dual‐stimuli. The synergistic effect of visible light and acid stimulation on the efficient release of anticancer drugs from the nanohybrids endows the system with great potential for cancer therapy.
Here, postfunctionalization and bioapplication of a π‐conjugated polymer named 4‐[4H‐dithieno(3,2‐b:2′,3′‐d)pyrrol‐4‐yl]aniline (DTP‐aryl‐NH2) are reported, which is successfully synthesized via electropolymerization onto the glassy carbon electrode. Folic acid (FA) is used to modify the amino functional polymer via N‐(3‐dimethylaminopropyl)‐N′‐ethylcarbodiimide hydrochloride/N‐hydroxysuccinimide chemistry for the further steps. The selective adhesion of folate receptor positive cells on the surface is followed by the electrochemical methods. Cyclic voltammetry and electrochemical impedance spectroscopy have been used to characterize stepwise modification of the electroactive surface. After optimization studies such as scan rate during the polymer deposition, FA amount for the efficient surface targeting, incubation time with the cells etc., analytical characterization is carried out. The surface morphologies at each step are imaged by using fluorescence microscopy.
The harmful Esca disease in vine plants caused by wood‐inhabiting fungi including Phaeomoniella chlamydospora (Pch) is spreading all across the world. This disease leads to poor vine crops and a slow decline or to a sudden dieback of the vine plants. The pruning wounds of vine plants are the main entry point for Pch. While model experiments with aerosol particles recommend electrospun nonwovens as a suitable barrier to block Pch, tests with living spores show clearly that only electrospun fibrous nonwovens do not prevent Pch invasion. However it is found, that with antifungal additives electrospun nonwovens could be applied successfully for blocking of Pch to infect the substrate. Thereby, a highly useful concept for the protection of vine plants against Esca disease is provided which could also serve as a concept for related plant diseases.
A stable polymeric network that mimics the highly polyanionic extracellular cartilage matrix still remains a great challenge. The main aim of this study is to present the synthesis of dendritic polyglycerol sulfate (dPGS)‐based in situ forming hydrogels using strain promoted azide‐alkyne cycloaddition reactions. A real time rheological study has been used to characterize the hydrogel properties. The viability of encapsulated human chondrocytes in the different hydrogels are monitored using live‐dead staining. Furthermore, type I and II collagen gene have been analyzed. Hydrogels with elastic moduli ranging from 1 to 5 kPa have been prepared by varying the dPGS amount. The chondrocyte viability in dPGS hydrogels is found to be higher than in pure PEG and alginate‐based hydrogels after 21 d. The higher cell viability in the dPGS engineered hydrogels can be explained by the fact that dPGS can interact with different proteins responsible for cell growth and proliferation.
Adhesion and proliferation of cells are often suppressed in rigid hydrogels as gel stiffness induces mechanical stress to embedded cells. Herein, the composite hydrogel systems to facilitate high cellular activities are described, while maintaining relatively high gel stiffness. This unusual property is obtained by harmonizing gelatin‐poly(ethylene glycol)‐tyramine (GPT, semisynthetic polymer) and gelatin‐hydroxyphenyl propionic acid conjugates (GH, natural polymer) into hydrogels. A minimum GH concentration of 50% is necessary for cells to be proliferative. GPT is utilized to improve biological stability (>1 week) and gelation time (<20 s) of the hydrogels. These results suggest that deficiency in cellular activity driven by gel stiffness could be overcome by finely tuning the material properties in the microenvironments.
To enhance drug cellular uptake, a biodegradable terpolymer is synthesized using taurine, N,N‐Bis (acryloyl) cystamine, and dodecylamine as raw materials by Michael addition terpolymerization. The terpolymer is transformed to zwitterionic nanoparticles (NPs) through self‐assembly. The surface charge of the NPs is convertible from negative at pH 7.4 to positive at pH 6.5, which endows the NPs’ excellent nonfouling feature in bloodstream and effective uptake in tumor cells. The NPs display varied morphologies from solid micelles to polymersomes and nanorods depending on molar ratios of the structural units involved. The NPs can be biodegraded in l ‐glutathione (GSH) solution due to the split of disulfide bonds in main chains of the terpolymers. The NPs demonstrate good pH/reducing responsiveness in drug delivery and can be potentially used as anticancer drug vehicles for enhancement of cellular uptake of anticancer drug.
A polyzwitterion is synthesized by regioselective functionalization of cellulose possessing a uniform charge distribution. The positively charged ammonium group is present at position 6, while the negative charge of carboxylate is located at positions 2 and 3 of the repeating unit. The molecular structure of the biopolymer derivative is proved by NMR spectroscopy. This cellulose‐based zwitterion is applied to several support materials by spin‐coating and characterized by means of atomic force microscope, contact angle measurements, ellipsometry, and X‐ray photoelectron spectroscopy. The coatings possess antimicrobial activity depending on the support materials (glass, titanium, tissue culture poly(styrene)) as revealed by confocal laser scanning microscopy and live/dead staining.
Furoxans, or 1,2,5‐oxadiazole‐N‐oxides, are a class of nitric oxide (NO)‐donating compounds that release NO in response to thiol‐containing molecules. In this study, polymeric micelles bearing furoxan moieties are prepared from an amphiphilic block copolymer consisting of a hydrophobic furoxan‐bearing block and a hydrophilic poly(N‐acryloylmorpholine) block. The block copolymer is prepared using a combination of the reversible addition–fragmentation chain transfer polymerization and the copper‐catalyzed Huisgen cycloaddition techniques. The block copolymers form spherical micelles with a diameter of 50 nm by self‐assembly in water. The micelles release NO in response to cysteine and show improved stability against hydrolytic decomposition. Furthermore, the micelles show a synergistic anti‐proliferative effect with ibuprofen in human colon cancer cells.
Microbial colonization of indwelling devices remains a major concern in modern healthcare. Developing approaches to prevent biomaterial‐associated infections (BAI) is, therefore, in great demand. This study aimed to immobilize two antimicrobial peptides (polymyxins B and E) onto polydimethylsiloxane (PDMS) using two polydopamine (pDA)‐based approaches: the conventional two‐step method involving the deposition of a pDA layer to which biomolecules are immobilized, and a one‐step method where peptides are dissolved together with dopamine before its polymerization. Surface characterization confirms the immobilization of polymyxins onto PDMS at a non‐toxic concentration. Immobilization of polymyxins using a one‐step pDA‐based approach is able to prevent Pseudomonas aeruginosa adhesion and kill a significant fraction of the adherent ones. Living cells adhered to these modified surfaces exhibit the same susceptibility pattern as cells adhered to unmodified surfaces, highlighting no resistance development. Results suggest that polymyxins immobilization holds a great potential as an additional antimicrobial functionality in the design of biomaterials.
Biopolymers are an attractive class of compounds for being used in biomedical applications as they are widely available from biomass. Their drawback is the lack of mechanical stability and the ability to tune this properly. Covalent chemical cross‐linking is an often used approach but it limits usability due to legislation as well as the need of advanced and specialized knowledge by end users such as clinicians. Here, increased and tunable mechanical properties are achieved of alginate‐based hydrogels with non‐covalent approaches using linear polyethyleneimine (LPEI) as a polyelectrolyte rather than only multivalent metal ions (Ca2+). Gel stiffness increases with increasing LPEI content. Gel morphology changes from a thin fibrous mesh for alginate‐Ca2+ to thicker fibrous networks when LPEI is introduced. The gels are able to efficiently release encapsulated small molecular dyes and the gels are able to host cells. For the cell encapsulation human skin fibroblasts (HSkF) and human bone marrow‐derived mesenchymal stem cells (hBM‐MSC) are used. HSkF can be successfully incorporated without diminished viability while the matrix components and gel preparation method are not compatible with hBM‐MSC. The newly developed alginate‐based system is regarded as a potential candidate for wound dressing materials.
Chondrocyte‐seeded, photo‐cross‐linked hydrogels prepared from solutions containing 50% mass fractions of methacrylated glycol chitosan or methacrylated hyaluronic acid (MHA) with methacrylated chondroitin sulfate (MCS) are cultured in vitro under static conditions over 35 d to assess their suitability for load‐bearing soft tissue repair. The photo‐cross‐linked hydrogels have initial equilibrium moduli between 100 and 300 kPa, but only the MHAMCS hydrogels retain an approximately constant modulus (264 ± 5 kPa) throughout the culture period. Visually, the seeded chondrocytes in the MHAMCS hydrogels are well distributed with an apparent constant viability in culture. Multicellular aggregates are surrounded by cartilaginous matrix, which contain aggrecan and collagen II. Thus, co‐cross‐linked MCS and MHA hydrogels may be suited for use in an articular cartilage or nucleus pulposus repair applications.
Molecularly Imprinted Polymers (MIPs) are highly advantageous in the field of analytical chemistry. However, interference from secondary molecules can also impede capture of a target by a MIP receptor. This greatly complicates the design process and often requires extensive laboratory screening which is time consuming, costly, and creates substantial waste products. Herein, is presented a new technique for screening of “virtually imprinted receptors” for rebinding of the molecular template as well as secondary structures, correlating the virtual predictions with experimentally acquired data in three case studies. This novel technique is particularly applicable to the evaluation and prediction of MIP receptor specificity and efficiency in complex aqueous systems.
There is a need for new and smart formulations that will help overcome the limitations of organic dyes used in photodynamic (PDT) and photothermal (PTT) therapy and significantly accelerate their clinical translation. Therefore the aim of this work was to create a responsive nanogel scaffold as a smart vehicle for dye administration. We developed a methodology that enables the conjugation of organic dyes to thermoresponsive nanogels and yields biocompatible, nanometer‐sized products with low polydispersity. The potential of the dye‐nanogel conjugate as a photothermal and photodynamic agent has been demonstrated by an in vitro evaluation with a model human carcinoma cell line. Additionally, confocal cell images showed their cellular uptake profile and their potential for bioimaging and intracellular drug delivery. These conjugates are a promising scaffold as a theranostic agents and will enable further applications in combination with controlled drug release.
A bioinspired adhesive material, polydopamine (pDA), was employed as an interfacial glue to stably immobilize human neural stem cells (hNSCs) on the external surface of biodegradable polycaprolactone (PCL) microspheres, thereby serving as versatile key systems that can be used for cell carriers. The pDA decoration on the PCL microspheres has been resulted in robust hNSC immobilization as well as proliferation on their curved surfaces. The pDA coating has transformed the hydrophobic PCL systems toward water‐friendly and sticky characteristics, thereby resulting in full dispersion in aqueous solution and stable adherence onto a wet biological surface. Adeno‐associated virus, a safe gene vector capable of effectively regulating cell behaviors, can be decorated on the PCL surfaces and delivered efficiently to hNSCs adhered to the microsphere exteriors. These distinctive multiple benefits of the sticky pDA microspheres can provide core technologies that can boost the therapeutic effects of cell therapy approaches.
The design of drug delivery systems capable of efficiently delivering poorly soluble drugs to target sites still remains a major challenge. Such materials require several different functionalities; typically, these materials should be biodegradable and nontoxic, nonimmunogenic, responsive to their environment, and soluble in aqueous solution while retaining the ability to solubilize hydrophobic drugs. Here, a polypeptide‐polymer hybrid of elastin‐like polypeptides (ELPs) and poly(2‐oxazoline)s (POx) is reported. This paper describes the chemical synthesis, physical characteristics, and drug loading potential of these novel hybrid macromolecules. A novel method is introduced for terminal functionalization of POx with protected maleimide moieties. Following recovery of the maleimide group via a retro Diels–Alder reaction, the consecutive Michael addition of thiol‐functionalized ELPs yields the desired protein‐polymer conjugate. These conjugates form nanoparticles in aqueous solution capable of solubilizing the anti‐cancer drug paclitaxel with up to 8 wt% loading.
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