Poly(ethylene glycol)‐poly(lactide) (PEG‐PLA) block copolymers are processed to solvent cast films and solution electrospun meshes. The effect of polymer composition, architecture, and number of anchoring points for the plasticizer on swelling, degradation, and mechanical properties of these films and meshes is investigated as potential barrier device for the prevention of peritoneal adhesions. As a result, adequate properties are achieved for the massive films with a longer retention of the plasticizer PEG for star‐shaped block copolymers than for the linear triblock copolymers and consequently more endurable mechanical properties during degradation. For electrospun meshes fabricated using the same polymers, similar trends are observed, but with an earlier start of fragmentation and lower tensile strengths. To overcome the poor mechanical strengths and an occurring shrinkage during incubation, which may impair the coverage of the wound, further adaptions of the meshes and the fabrication process are necessary.
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.
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.
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.
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.
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.
This study reports the structural transition of electrospun poly(ε‐caprolactone) (PCL)/poly[(propylmethacryl‐heptaisobutyl‐polyhedral oligomeric silsesquioxane)‐co‐(methyl methacrylate)] (POSS‐MMA) blends, from PCL‐rich fibers, to bicontinuous PCL core/POSS‐MMA shell fibers, to POSS‐MMA‐rich fibers with a discontinuous PCL inner phase. A ternary phase diagram depicting the electrospinnability of PCL/POSS‐MMA solutions is constructed by evaluating the morphological features of fibers electrospun from solutions with various concentrations and PCL/POSS‐MMA blend ratios. X‐ray diffraction, Raman spectroscopy, and differential scanning calorimetry are further used to characterize the electrospun PCL/POSS‐MMA hybrid fibers. These physicochemical characterization results are thoroughly discussed to understand the internal structures of the hybrid fibers, which are directly correlated to the phase separation behavior of the electrospun solutions. The current study provides further insight into the complex phase behavior of POSS‐copolymer‐based systems, which hold great potential for a broad spectrum of biomedical applications.
Electrospun fibers of hydrophilic polymers meet challenges in a rapid degradation of fiber matrices and discharge of antibiotics to comply with requirements of infection control as a dermal regeneration template. In the current study, a pH conversion process is initially developed to ensure fluent electrospinning, an efficient in situ cross‐linking of electrospun gelatin fibers with oxidized alginate and simultaneous loading of gentamicin sulfate (GS) and hydrophobic ciprofloxacin into fibers. The dual drug‐loaded fibers indicate a complete release of GS during 6 d and a sustained release of ciprofloxacin for over three weeks, and the antibiotics release indicates significant growth inhibitions on Pseudomonas aeruginosa and Staphylococcus epidermidis. The wound healing efficacy is evaluated on a deep burn model infected with 108 CFU of P. aeruginosa. Compared with fibers with loaded individual drugs, the concomitant release of GS and ciprofloxacin significantly reduces the bacteria numbers in wound and livers, at around 2.30 × 105 and 1.25 × 103 CFU after 3 d, respectively. The wound re‐epithelization, blood vessel formation, collagen deposition, and tissue remodeling process are accelerated with a complete healing observed after 21 d. This study provides a feasible strategy to design cross‐linked hydrophilic fibers with an extended drug release for biomedical applications.
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.
Three‐dimensional hydrogel supports for mesenchymal and neural stem cells (NSCs) are promising materials for tissue engineering applications such as spinal cord repair. This study involves the preparation and characterization of superporous scaffolds based on a copolymer of 2‐hydroxyethyl and 2‐aminoethyl methacrylate (HEMA and AEMA) crosslinked with ethylene dimethacrylate. Ammonium oxalate is chosen as a suitable porogen because it consists of needle‐like crystals, allowing their parallel arrangement in the polymerization mold. The amino group of AEMA is used to immobilize RGDS and SIKVAVS peptide sequences with an N‐γ‐maleimidobutyryloxy succinimide ester linker. The amount of the peptide on the scaffold is determined using 125I radiolabeled SIKVAVS. Both RGDS‐ and SIKVAVS‐modified poly(2‐hydroxyethyl methacrylate) scaffolds serve as supports for culturing human mesenchymal stem cells (MSCs) and human fetal NSCs. The RGDS sequence is found to be better for MSC and NSC proliferation and growth than SIKVAVS.
Glycodendrimers based on aromatic cores have an amphiphilic character and have been reported to generate supramolecuar assemblies in water. A new group of glycodendrimers with an aromatic rod‐like core were recently described as potent antagonists of DC‐SIGN‐mediated viral infections. A full characterization of the aggregation properties of these materials is presented here. The results show that these compounds exist mostly as monomers in water solution, in dynamic equilibrium with small aggregates (dimers or trimers). Larger aggregates observed by dynamic light scattering and transmission Electron Microscopy for some of the dendrimers are found to be portions of materials not fully solubilized and can be removed either by optimizing the dissolution protocol or by centrifugation of the samples.
Pinosylvin is a natural stilbenoid known to exhibit antibacterial bioactivity against foodborne bacteria. In this work, pinosylvin is chemically incorporated into a poly(anhydride‐ester) (PAE) backbone via melt‐condensation polymerization, and characterized with respect to its physicochemical and thermal properties. In vitro release studies demonstrate that pinosylvin‐based PAEs hydrolytically degrade over 40 d to release pinosylvin. Pseudo‐first order kinetic experiments on model compounds, butyric anhydride and 3‐butylstilbene ester, indicate that the anhydride linkages hydrolyze first, followed by the ester bonds to ultimately release pinosylvin. An antibacterial assay shows that the released pinosylvin exhibit bioactivity, while in vitro cytocompatibility studies demonstrate that the polymer is noncytotoxic toward fibroblasts. These preliminary findings suggest that the pinosylvin‐based PAEs can serve as food preservatives in food packaging materials by safely providing antibacterial bioactivity over extended time periods.
Thin polymer films that prevent the adhesion of bacteria are of interest as coatings for the development of infection‐resistant biomaterials. This study investigates the influence of grafting density and film thickness on the adhesion of Staphylococcus epidermidis to poly(poly(ethylene glycol)methacrylate) (PPEGMA) and poly(2‐hydroxyethyl methacrylate) (PHEMA) brushes prepared via surface‐initiated atom transfer radical polymerization (SI‐ATRP). These brushes are compared with poly(ethylene glycol) (PEG) brushes, which are obtained by grafting PEG onto an epoxide‐modified substrate. Except for very low grafting densities (ρ = 1%), crystal violet staining experiments show that the PHEMA and PPEGMA brushes are equally effective as the PEG‐modified surfaces in preventing S. epidermis adhesion and do not reveal any significant variations as a function of film thickness or grafting density. These results indicate that brushes generated by SI‐ATRP are an attractive alternative to grafted‐onto PEG films for the preparation of surface coatings that resist bacterial adhesion.
Given alginate's contribution to Pseudomonas aeruginosa virulence, it has long been considered a promising target for interventional therapies, which have been performed by using the enzyme alginate lyase. In this work, instead of treating pre‐established mucoid biofilms, alginate lyase is immobilized onto a surface as a preventive measure against P. aeruginosa adhesion. A polydopamine dip‐coating strategy is employed for functionalization of polycarbonate surfaces. Enzyme immobilization is confirmed by surface characterization. Surfaces functionalized with alginate lyase exhibit anti‐adhesive properties, inhibiting the attachment of the mucoid strain. Moreover, surfaces modified with this enzyme also inhibit the adhesion of the tested non‐mucoid strain. Unexpectedly, treatment with heat‐inactivated enzyme also inhibits the attachment of mucoid and non‐mucoid P. aeruginosa strains. These findings suggest that the antibacterial performance of alginate lyase functional coatings is catalysis‐independent, highlighting the importance of further studies to better understand its mechanism of action against P. aeruginosa strains.
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.
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.
An efficiently siRNA transporting nanocarrier still remains to be developed. In this study, utilizing the dual stimulus of acid tumor extracellular environment and redox effect of glutathione in the cytosol, a new siRNA transporting system combining triple effects of folate targeting, acid sensitive polymer micelles, and bio‐reducible disulfide bond linked siRNA‐cell penetrating peptides (CPPs) conjugate is developed to suppress c‐myc gene expression of breast cancer (MCF‐7 cells) both in vitro and in vivo. Subsequent research demonstrates that the vesicle has particle size of about 100 nm and siRNA entrapment efficiency of approximately 80%. In vitro studies verified over 90% of encapsulated siRNA‐CPPs can be released and the vesicle shows higher cellular uptake in response to the tumorous zone. Determination of gene expression at both mRNA and protein levels indicates the constructed vesicle exhibited enhanced cancer cell apoptosis and improved therapeutic efficacy in vitro and in vivo.
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.
In order to construct unique polypeptide architectures, a novel telechelic‐type initiator with two leucine ethyl ester units is designed for chemoenzymatic polymerization. Glycine or alanine ethyl ester is chemoenzymatically polymerized using papain in the presence of the initiator, and the propagation occurs at each leucine ethyl ester unit to produce the telechelic polypeptide. The formation of the telechelic polypeptides is confirmed by 1H NMR and MALDI‐TOF mass spectroscopies. It is revealed by AFM observation that long nanofibrils are formed from the telechelic polyalanine, whereas a conventional linear polyalanine with a similar degree of polymerization shows granule‐like structures. The telechelic polyglycine and polyalanine show the crystalline structures of Polyglycine II and antiparallel β‐sheet, respectively. It is demonstrated that this method to synthesize telechelic‐type polypeptides potentially opens up a pathway to construct novel hierarchical structures by self‐assembly.
Growth factors are potent signaling proteins for tissue engineering, but they are susceptible to loss of activity when exposed to solvents used for polymer processing. This work explores preservation of fibroblast growth factor‐2 (FGF‐2) activity in chitosan nanofibers using two‐phase electrospinning via a compound coaxial needle and from a water‐in‐oil emulsion FGF‐2 in aqueous poly(vinyl alcohol) is added on either the inside (A/O) or the outside (O/A) of an organic chitosan phase, using the compound needle. FGF‐2 is further stabilized by complexation to heparin‐based nanoparticles. The emulsion method does not result in detectable incorporation of FGF‐2. The A/O fibers incorporate the highest amount of FGF‐2. Nanoparticle‐stabilized FGF‐2 in A/O nanofibers is most active toward bone‐marrow stromal cells.
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