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.
The use of light‐sensitive polymers for the release of therapeutics is an important approach allowing the timing and amount of the release to be controlled precisely. The use of light has been pioneered to control insulin release from a dermal photoactivated depot, or PAD. One of the main impediments to the use of light‐sensitive polymers in this context is the density of the materials: The large majority of the material is the carrier polymer, with the minority being the therapeutic. In this work, the feasibility of using insulin itself as a monomer in the polymerization process is demonstrated. Insulin modified with either one or two light cleavable azide groups is polymerized with a tridentate alkyne‐bridging monomer using a click reaction. The resulting material called a “macropolymer” is ≈85% insulin, is insoluble in aqueous solvent, and releases native, soluble insulin upon irradiation.
New antimicrobial materials will be more and more in the focus for hygienic and clinical disease control. Antimicrobial materials have to be distinguished in leaching and nonleaching materials. For many applications of antimicrobial materials on implants the use of nonleaching materials is essential. Therefore, the antimicrobial efficiency of leaching and nonleaching polymers has been investigated quantitatively in vitro in direct comparison on a highly relevant implant of central venous catheters (CVCs) using a well‐established called Certika test. This test is especially designed to test antimicrobial properties of leachable and nonleachable materials. This contribution demonstrates that newly developed nonleaching antimicrobial CVCs are equivalent to conventional leaching CVC systems in their antimicrobial performance against gram‐positive and gram‐negative bacteria, as well as Candida species. The use of new nonleaching antimicrobial polymers as shown here for CVCs represents a different mode of action with the aim to prevent infections also with antibiotic‐resistant strains and reduced side effects.
Traditionally, conductive materials for electrodes are based on high modulus metals or alloys. Development of bioelectrodes that mimic the mechanical properties of the soft, low modulus tissues in which they are implanted is a rapidly expanding field of research. Many polymers exist that more closely match tissue mechanics than metals; however, the majority do not conduct charge. Integrating conductive properties via incorporation of metals and other conductors into nonconductive polymers is a successful approach to producing polymers that can be used in electrical interfacing devices. When combining conductive materials with nonconductive polymer matrices, there is often a tradeoff between the electrical and mechanical properties. This review analyzes the advantages and disadvantages of approaches involving coating or layer formation, composite formation via dispersion of conductive inclusions through polymer matrices, and in situ growth of a conductive network within polymers.
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.
There is a growing interest in modern healthcare to develop systems able to fight antibiotic resistant bacteria. Antimicrobial cationic biodegradable polymers able to mimic antimicrobial peptides have shown to be effective against both Gram‐positive and Gram‐negative bacteria. In these systems, the hydrophilic–hydrophobic ratio and the cationic charge density play a pivotal role in defining the killing efficiency. Nevertheless, many of these antimicrobial polymers show relatively low selectivity as defined by the relative toxicity to mammalian cells or hemolysis relative to pathogens. In this study, a series of polycarbonates containing pendant quaternary ammoniums are used to understand the role of different counter‐anions including chloride, citrate, malonate, benzoate, acetate, lactate and trifluoroacetate, and the antibiotic penicillin on antimicrobial efficacy and selectivity. Interestingly, it is found that in spite of the strong antimicrobial activity of trifluoroacetate and benzoate anions, they prove to be much less hemolytic than chloride anion. It is believed that the proper selection of the anion could enhance the potential of antimicrobial polymers to fight against clinically relevant pathogenic infections, while concurrently mitigating harmful side effects.
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.
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.
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.
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.
Biosensing is an important and rapidly developing field, with numerous potential applications in health care, food processing, and environmental control. Polymer–graphene nanocomposites aim to leverage the unique, attractive properties of graphene by combining them with those of a polymer matrix. Molecular imprinted polymers, in particular, offer the promise of artificial biorecognition elements. A variety of polymers, including intrinsically conducting polymers (polyaniline, polypyrrole), bio‐based polymers (chitosan, polycatechols), and polycationic polymers (poly(diallyldimethylammonium chloride), polyethyleneimine), have been utilized as matrices for graphene‐based nanofillers, yielding sensitive biosensors for various biomolecules, such as proteins, nucleic acids, and small molecules.
A collagen sheet with highly aligned collagen fibers is fabricated by continuous cyclic stretch. The rearrangement of the collagen fibers depends on the different process parameters of the cyclic stretch, including magnitude, frequency, and period of stretch. The collagen fibers are aligned perpendicularly to the direction of the stretch. Corneal stromal cells and smooth muscle cells cultivated on the highly aligned collagen sheet show alignment along the collagen fibers without the stretch during culture. Thus, the sheet can be a suitable scaffold for use in regenerative medicine.
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.
A new synthetic method for the production of artificial magnetosomes, i.e., lipid‐coated vesicles containing magnetic nanoparticles, is demonstrated. Magnetosomes have considerable potential in biomedical and other nanotechnological applications but current production methods rely upon magnetotactic bacteria which limits the range of sizes and shapes that can be generated as well as the obtainable yield. Here, electrohydrodynamic atomization is utilized to form nanoscale liposomes of tunable size followed by electroporation to transport iron into the nanoliposome core resulting in magnetite crystallization. Using a combination of electron and fluorescence microscopy, dynamic light scattering, Raman spectroscopy, and magnetic susceptibility measurements, it is shown that single crystals of single‐phase magnetite can be precipitated within each liposome, forming a near‐monodisperse population of magnetic nanoparticles. For the specific conditions used in this study the mean particle size is 58 nm (±8 nm) but the system offers a high degree of flexibility in terms of both the size and composition of the final product.
Reactive oxygen species (ROS) play important roles in cell signaling pathways, while increased production of ROS may disrupt cellular homeostasis, giving rise to oxidative stress and a series of diseases. Utilizing these cell‐generated species as triggers for selective tuning polymer structures and properties represents a promising methodology for disease diagnosis and treatment. Recently, significant progress has been made in fabricating biomaterials including nanoparticles and macroscopic networks to interact with this dynamic physiological condition. These ROS‐responsive platforms have shown potential in a range of biomedical applications, such as cancer targeted drug delivery systems, cell therapy platforms for inflammation related disease, and so on.
Development of artificial tissues providing the proper geometrical, mechanical, and environmental cues for cells is highly coveted in the field of tissue engineering. Recently, microfabrication strategies in combination with other chemistries have been utilized to capture the architectural complexity of intricate organs, such as the liver, in in vitro platforms. Here it is shown that a biofunctionalized poly (ethylene glycol) (PEG) hydrogel scaffold, fabricated using a sphere‐template, facilitates hepatic sheet formation that follows the microscale patterns of the scaffold surface. The design takes advantage of the excellent diffusion properties of porous, uniform 3D hydrogel platforms, and the enhanced‐cell–extracellular matrix interaction with the display of conjugated collagen type I, which in turn elicits favorable Huh‐7.5 response. Collectively, the experimental findings and corresponding simulations demonstrate the importance of biofunctionalized porous scaffolds and indicate that the microscaffold shows promise in liver tissue engineering applications and provides distinct advantages over current cell sheet and hepatocyte spheroid technologies.
Gelatin nanoparticles can be tuned with respect to their drug loading efficiency, degradation rate, and release kinetics, which renders these drug carriers highly suitable for a wide variety of biomedical applications. The ease of functionalization has rendered gelatin an interesting candidate material to introduce specific motifs for selective targeting to specific organs, but gelatin nanoparticles have not yet been modified to increase their affinity to mineralized tissue. By means of conjugating bone‐targeting alendronate to biocompatible gelatin nanoparticles, a simple method is developed for the preparation of gelatin nanoparticles which exhibit strong affinity to mineralized surfaces. It has been shown that the degree of alendronate functionalization can be tuned by controlling the glutaraldehyde crosslinking density, the molar ratio between alendronate and glutaraldehyde, as well as the pH of the conjugation reaction. Moreover, it has been shown that the affinity of gelatin nanoparticles to calcium phosphate increases considerably upon functionalization with alendronate. In summary, gelatin nanoparticles have been developed, which exhibit great potential for use in bone‐specific drug delivery and regenerative medicine.
To simultaneously control inflammation and facilitate dentin regeneration, a copolymeric micelle‐in‐microsphere platform is developed in this study, aiming to simultaneously release a hydrophobic drug to suppress inflammation and a hydrophilic biomolecule to enhance odontogenic differentiation of dental pulp stem cells in a distinctly controlled fashion. A series of chitosan‐graft‐poly(lactic acid) copolymers is synthesized with varying lactic acid and chitosan weight ratios, self‐assembled into nanoscale micelle‐like core–shell structures in an aqueous system, and subsequently crosslinked into microspheres through electrostatic interaction with sodium tripolyphosphate. A hydrophobic biomolecule either coumarin‐6 or fluocinolone acetonide (FA) is encapsulated into the hydrophobic cores of the micelles, while a hydrophilic biomolecule either bovine serum albumin or bone morphogenetic protein 2 (BMP‐2) is entrapped in the hydrophilic shells and the interspaces among the micelles. Both hydrophobic and hydrophilic biomolecules are delivered with distinct and tunable release patterns. Delivery of FA and BMP‐2 simultaneously suppresses inflammation and enhances odontogenesis, resulting in significantly enhanced mineralized tissue regeneration. This result also demonstrates the potential for this novel delivery system to deliver multiple therapeutics and to achieve synergistic effects.
Biodegradable self‐assembled polymeric nanoparticles (NPs) composed of poly(6‐O‐methacryloyl‐D‐galactopyranose)‐b‐poly(L‐lactide)‐b‐poly(6‐O‐methacryloyl‐D‐galactopyranose) (PMAGP‐b‐PLA‐b‐PMAGP) are prepared as carriers for the hydrophobic anticancer drug paclitaxel (PTX), to achieve target delivery to hepatoma cells. PTX can be encapsulated by the NPs with various molar ratios of L‐lactide (LA) and 6‐O‐methacryloyl‐D‐galactopyranose (MAGP) during the process of self‐assembly, and the resulting NPs exhibit high drug loading efficacy and substantial stability in aqueous solution. The size, size distribution, and morphology of the NPs are characterized using a Zetasizer Nano ZS and transmission electron microscopy. The hemolysis assay and cell cytotoxicity assay indicate that the polymeric NPs are biocompatible and non‐toxic. The cellular uptake assay demonstrates that the galactose‐containing NPs can be selectively recognized and subsequently accumulate in HepG2 cells. All of these results demonstrate that galactose‐containing polymeric NPs are potential carriers for hepatoma‐targeted drug delivery and liver cancer therapy in clinical medicine.
For the design of a biohybrid structure as a ligand‐tailored drug delivery system (DDS), it is highly sophisticated to fabricate a DDS based on smoothly controllable conjugation steps. This article reports on the synthesis and the characterization of biohybrid conjugates based on noncovalent conjugation between a multivalent biotinylated and PEGylated poly(amido amine) (PAMAM) dendrimer and a tetrameric streptavidin‐small protein binding scaffold. This protein binding scaffold (SA‐ABDwt) possesses nM affinity toward human serum albumin (HSA). Thus, well‐defined biohybrid structures, finalized by binding of one or two HSA molecules, are available at each conjugation step in a controlled molar ratio. Overall, these biohybrid assemblies can be used for (i) a controlled modification of dendrimers with the HSA molecules to increase their blood‐circulation half‐life and passive accumulation in tumor; (ii) rendering dendrimers a specific affinity to various ligands based on mutated ABD domain, thus replacing tedious dendrimer–antibody covalent coupling and purification procedures.
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