查看更多>>摘要：Abstract The synthesis of polymeric nanoparticles from a block copolymer based on poly(ethylene glycol) and a polymethacrylate containing the nucleobase analog 2,6‐diacylaminopyridine is optimized by microfluidics to obtain homogeneous spherical micelles. Loading and delivery properties are studied using naproxen as a model. The incorporation of a Pd precursor in the polymer organic solution fed into the micromixer allows the preparation of Pd(II) precursor‐polymer hybrid systems and the subsequent reduction with CO leads to the in situ synthesis of Pd nanosheets inside of the hydrophobic core of the polymeric micelles. This methodology is highly efficient to yield all polymeric nanoparticles loaded with Pd nanosheets as detected by electron microscopy and energy‐dispersive X‐ray spectroscopy. The cell viability of these Pd nanosheets‐containing polymeric nanoparticles is evaluated using five cell lines, showing a high cytocompatibility at the tested concentrations without detrimental effects in cell membrane and nuclei. Furthermore, the use of these hybrid polymeric nanoparticles as photothermal transductors is evaluated using near infrared as irradiation source as well as its application in photothermal therapy using different cell lines demonstrating a high efficiency in all cell cultures.
Erika L. CyphertNithya KanagasegarNingjing ZhangGreg D. Learn...
12页
查看更多>>摘要：Abstract Primary bone tumor resections often result in critical size defects, which then necessitate challenging clinical management approaches to reconstruct. One such intervention is the Masquelet technique, in which poly(methyl methacrylate) (PMMA) bone cement is placed as a spacer temporarily while adjuvant chemotherapeutics are administered systemically. The spacer is later removed and replaced with bone autograft. Local recurrence remains an important and devastating problem, therefore, a system capable of locally delivering chemotherapeutics will present unique advantages. In this work, a refillable chemotherapeutic (doxorubicin, DOX) delivery platform comprised of PMMA bone cement and insoluble γ‐cyclodextrin (γ‐CD) polymeric microparticles is developed and explored towards application as a temporary adjuvant chemotherapeutic spacer. The system is characterized for porosity, mechanical strength, DOX filling and refilling capacity, elution kinetics, and cytotoxicity. Since residual chemotherapeutics can adversely impact bone healing, it is important that virtually all DOX be released from material. Composites containing 15 wt% γ‐CD microparticles demonstrate 100% DOX release within 100 days, whereas only 6% DOX is liberated from PMMA with free DOX over same period. Refillable properties of PMMA composite system may find utility for customizing dosing regimens. Findings suggest that PMMA composites can have potential as chemotherapeutic delivery platforms to assist in bone reconstruction.
Lena WitzdamYannick L. MeurerManuela Garay‐SarmientoMariia Vorobii...
10页
查看更多>>摘要：Abstract Interfacing artificial materials with biological tissues remains a challenge. The direct contact of their surface with the biological milieu results in multiscale interactions, in which biomacromolecules adsorb and act as transducers mediating the interactions with cells and tissues. So far, only antifouling polymer brushes have been able to conceal the surface of synthetic materials. However, their complex synthesis has precluded their translation to applications. Here, it is shown that ultrathin surface‐attached hydrogel coatings of N‐(2‐hydroxypropyl) methacrylamide (HPMA) and carboxybetaine methacrylamide (CBMAA) provide the same level of protection as brushes. In spite of being readily applicable, these coatings prevent the fouling from whole blood plasma and provide a barrier to the adhesion of Gram positive and negative bacteria. The analysis of the components of the surface free energy and nanoindentation experiments reveals that the excellent antifouling properties stem from the strong surface hydrophilicity and the presence of a brush‐like structure at the water interface. Moreover, these coatings can be functionalized to achieve antimicrobial activity while remaining stealth and non‐cytotoxic to eukaryotic cells. Such level of performance is previously only achieved with brushes. Thus, it is anticipated that this readily applicable strategy is a promising route to enhance the biocompatibility of real biomedical devices.
查看更多>>摘要：Abstract Noncovalent interactions among short peptides and proteins lead to their molecular self‐assembly into supramolecular packaging, which provides the fundamental basis of life. These biomolecular assemblies are highly susceptible to the environmental conditions, including temperature, light, pH, and ionic concentration, and thus inspiring the fabrication of a new class of stimuli‐responsive biomaterials. Here, for the first time the cooperative effect of the divalent metal ions to promote hydrogelation in the short collagen inspired self‐assembling peptide for developing advanced biomaterials is reported. Introduction of the biologically relevant metal ions (Ca2+/Mg2+) to the peptide surpasses its limitation to self‐assemble into a multiscale structure at physiological pH. In particular, in presence of metal ions, the negatively charged peptide shows a distinct shift in its equilibrium point of gelation and demonstrates conversion from sol to gel and thus enabling the scope of fabricating an advanced biomaterial for controlling cellular behavior. Interestingly, tunable mechanical strength and improved cellular response are observed within ion‐coordinated peptide hydrogels compared to the peptide gelator. Microscopic analyses, rheological assessment, and biological studies establish the importance of utilizing a novel strategy by simply using metal ions to modulate the physical and biological attributes of collagen inspired peptide (CIPs) to construct next‐generation biomaterials.
Sarah S. KermaniyanMoore ChenChanghe ZhangSamuel A. Smith...
10页
查看更多>>摘要：Abstract pH‐responsive nanoparticles have generated significant interest for use as drug delivery systems due to their potential for inducible release at low pH. The pH variation from the bloodstream (pH 7.4) to intracellular compartments of cells called endosomes/lysosomes (pH <?5.0) has been of particular interest. However, one of the limitations with nanoparticle delivery systems is the inability to migrate out of these compartments to the cytosol or other organelles, via a process termed endosomal escape. Previous studies have postulated that pH‐responsive nanoparticles can facilitate endosomal escape through a range of mechanisms including membrane interaction, pH‐induced swelling, and the proton‐sponge effect. In this study, a series of pH‐swellable nanoparticles (85–100?nm) are designed and their impact on biological interactions, particularly endosomal escape, are investigated. The particles exhibit tunable pH‐induced swelling (from 120% to 200%) and have good buffering capacity. The cellular association is studied using flow cytometry and endosomal escape is determined using a calcein leakage assay. Interestingly, no endosomal escape with all nanoparticle formulations is found, which suggests there are limitations with both the proton‐sponge effect and pH‐induced swelling mechanism as the primary methods for inducing endosomal escape.
查看更多>>摘要：Abstract Recently, photodynamic therapy (PDT) has become a promising approach for the treatment of a broad range of diseases, including oncological and infectious diseases. This minimally invasive and localized therapy is based on the production of reactive oxygen species able to destroy cancer cells and inactivate pathogens by combining the use of photosensitizers (PSs), light, and molecular oxygen. To overcome the drawbacks of drug systemic administration, drug delivery systems (DDS) can be used to carrier the PSs, allowing higher therapeutic efficacy and minimal toxicological effects. Polymeric nanofibers produced by electrospinning emerged as powerful platforms for drug delivery applications. Electrospun nanofibers exhibit outstanding characteristics, such as large surface‐area‐to‐volume ratio associated with high drug loading, high porosity, flexibility, ability to incorporate and release a wide variety of therapeutic agents, biocompatibility, and biodegradability. Due to the versatility of this technique, fibers with different morphologies and functionalities, including drug release profile can be produced. The possibility of scalability makes electrospinning even more attractive for the development of DDS. This review aims to explore and show an up to date of the huge potential of electrospun nanofibers as DDS for different PDT applications and discuss the opportunities and challenges in this field.
查看更多>>摘要：Abstract Due to lack of amino sugar with aging, people will suffer from various epidemic bone diseases called “undead cancer” by the World Health Organization. The key problem in bone tissue engineering that is not completely resolved is the repair of critical large‐scale bone and cartilage defects. The chirality of the extracellular matrix plays a decisive role in the physiological activity of bone cells and the occurrence of bone tissue, but the mechanism of chirality in regulating cell adhesion and growth is still in the early stage of exploration. The application progress of chirality‐induced bionic scaffolds is reviewed here in bone defects repair based on “soft” and “hard” scaffolds. The aim is to summarize the effects of different chiral structures (l‐shaped and d‐shaped) in the process of inducing bionic scaffolds in bone defects repair. In addition, many technologies and methods as well as issues worthy of special consideration for preparing chirality‐induced bionic scaffolds are also introduced. It is expected that this work can provide inspiring ideas for designing new chirality‐induced bionic scaffolds and promote the development of chirality in bone tissue engineering.
查看更多>>摘要：Abstract The reconstituted motility system of actin‐myosin is expected to be used in bioinspired transport devices, in which carried materials are attached to either moving actin filaments or walking myosin molecules. However, the dependence of the ability to transport on the size of the attached materials is still inadequately understood. Here, as carried materials, polyethylene glycols (PEGs) of various sizes are covalently bound to actin filaments, and the motility of PEG‐attached filaments on a heavy meromyosin (HMM) immobilized on a glass surface is observed via fluorescence microscopy. Full attachment of 2?kDa PEG, with an approximately 2?nm gyration radius, decreases the velocity and fraction of moving actin filaments by approximately 10% relative to unattached filaments. For the 5?kDa PEG, the fraction of moving filaments is decreased by approximately 70% even when the filaments contain only 20% PEG‐attached actin. The attachment of both sizes of PEGs suppresses the actin‐activated ATPase activity at the same level. These results suggest that actin filaments can carry PEGs up to 2?kDa having the same size as actin monomers, while the rate of ATP hydrolysis is limited. The size dependence may provide a criterion for material delivery via actin filaments in nanotransport applications.
查看更多>>摘要：Abstract Chitosan has been utilized as a popular biopolymer to fabricate hydrogels for biomedical applications. However, chitosan hydrogels are generally too brittle to mimic the deformability of the extracellular matrix in many tissues and organs. In particular, the role of the varied crosslinkers in determining the elasticity of chitosan hydrogels is lack of discussion. Here, three aldehyde‐functionalized crosslinkers (i.e., aldehyde‐modified poly(xylitol sebacate)‐co‐poly(ethylene glycol) (APP), glutaraldehyde (GA), and polydextran aldehyde (PDA)) are used to react with quaternized chitosan (QCS) through imine bonds to form hydrogels. The microstructures, mechanical performances, and cytocompatibility of the three hydrogels are systematically investigated. The APP/QCS hydrogels presented the best compressive and stretch properties among the three hydrogels. The mechanical property and antibacterial activity of APP/QCS hydrogels can be further modulated using varied QCS amounts, where more QCS contributed higher stiffness and stretchability as well as better bacterial inhibition to the APP/QCS hydrogels. Taken together, it is demonstrated that the inherent elastomeric characteristic of APP crosslinker provides the desirable elasticity and stretchability to QCS hydrogels compared to the other aldehyde‐functionalized crosslinkers of GA and PDA. This strategy of using multivalent elastomeric crosslinkers to fabricate deformable chitosan hydrogels can expand the use of chitosan hydrogels in tissue engineering applications.
NSTL
Wiley