To date, lack of functional hydrogel inks has limited 3D printing applications in tissue engineering. This study developed a series of photocurable hydrogel inks based on chitooligosaccharide ...(COS)‐polyethylene glycol diacrylate (PEGDA) for extrusion‐based 3D printing of bone tissue scaffolds. The scaffolds were prepared by aza‐Michael addition of COS and PEGDA followed by photopolymerisation of unreacted PEGDA. The hydrogel inks showed sufficient shear thinning properties required for extrusion 3D printing. The printed scaffolds exhibited excellent shape fidelity and fine microstructure with a resolution of 250 μm. By increasing the COS content, the swelling ratio of the scaffolds decreased, while the compressive strength increased. 3D printed COS‐PEGDA scaffolds showed high viability of human bone mesenchymal stem cells in vitro. In addition, scaffolds containing 2 wt% COS showed significantly higher alkaline phosphatase activity, calcium deposition, and bioactivity in simulated body fluid compared to the control (PEGDA). Altogether, 3D printed COS‐PEGDA scaffolds represent promising candidates for bone tissue regeneration.
A novel triblock copolymer for use in an injectable pH- and temperature-sensitive hydrogel is synthesized by conjugating poly(amidoamine) (PAA) to poly(ethylene glycol): ...poly(amidoamine)-poly(ethylene glycol)-poly(amidoamine) (PAA-PEG-PAA). The polymer was characterized with 1H NMR and gel permeation chromatography in the diluents CDCl3 and CHCl3, respectively. The PAA block acts as a pH- and temperature-sensitive block. The PAA-PEG-PAA copolymer in aqueous solution (12.5 wt %) underwent a sol−gel transition as a function of pH and temperature. After injection into a rat, the copolymer solution (12.5 wt %) was immediately changed to a gel.
Hydrogels possess high water content and closely mimic the microenvironment of extracellular matrix. In this study, we created a hybrid hydrogel containing type II collagen, hyaluronic acid (HA), and ...polyethylene glycol (PEG) and incorporated magnetic nanoparticles into the hybrid hydrogels of type II collagen-HA-PEG to produce a magnetic nanocomposite hydrogel (MagGel) for cartilage tissue engineering. The results showed that both the MagGel and hybrid gel (Gel) were successfully cross-linked and the MagGel responded to an external magnet while maintaining structural integrity. That is, the MagGel could travel to the tissue defect sites in physiological fluids under remote magnetic guidance. The adhesion density of bone marrow derived mesenchymal stem cells (BMSCs) on the MagGel group in vitro was similar to the control group and greater than the Gel group. The morphology of BMSCs was normal and consistent in all groups. We also found that BMSCs engulfed magnetic nanoparticles in culture and the presence of magnetic nanoparticles did not affect BMSC adhesion and morphology. We hypothesized that the ingested nanoparticles may be eventually broken down by lysosome and excreted through exocytosis; further studies are necessary to confirm this. This study reports a promising magnetic responsive nanocomposite hydrogel for potential cartilage tissue engineering applications, which should be further studied for its effects on cell functions when combined with electromagnetic stimulation.
Pre-existing antibodies that bind polyethylene glycol are present in about 40% of healthy individuals. It is currently unknown if pre-existing anti-polyethylene glycol (PEG) antibodies can alter the ...bioactivity of pegylated drugs with a single long PEG chain, which represents the majority of newly developed pegylated medicines. Methoxy polyethylene glycol-epoetin beta (PEG-EPO) contains a single 30 kDa PEG chain and is used to treat patients suffering from anemia. We find that the pre-existing human anti-PEG IgM and IgG antibodies from normal donors can bind to PEG-EPO. The prevalence and concentrations of anti-PEG IgM and IgG antibodies were also higher in patients that responded poorly to PEG-EPO. Monoclonal anti-PEG IgM and IgG antibodies at concentrations found in normal donors blocked the biological activity of PEG-EPO to stimulate the production of new erythrocytes in mice and accelerated the clearance of
I-PEG-EPO, resulting in PEG-EPO accumulation primarily in the liver and spleen. Accelerated clearance by the anti-PEG IgG antibody was mediated by the Fc portion of the antibody. Importantly, infusing higher doses of PEG-EPO could compensate for the inhibitory effects of anti-PEG antibodies, suggesting that pre-existing anti-PEG antibodies can be "dosed through." Our study indicates that the bioactivity and therapeutic activity of PEG-EPO may be reduced in patients with elevated levels of pre-existing anti-PEG antibodies. New pegylated medicines with a single long PEG chain may also be affected in patients with high levels of anti-PEG antibodies.
Objectives: Gold nanoparticles are very popular metallic nanomaterials and they have a wide spectrum of biomedical applications. This study was aimed to the production of stable and monodisperse ...polyethyleneimine (PEI) and polyethylene glycol (PEG) coated gold nanoparticles (AuNP20 and AuNP50), investigation of their in vivo biochemical effects in the BALB/c mice.
Methods: Gold nanoparticles were synthesized and their surfaces were modified by PEI and PEG. All the necessary physicochemical characterizations were performed. After the single high dose i.v. injection (5 mg Au/kg animal weight) of the AuNP groups, their in vivo biochemical effects were evaluated multiparametrically in the mice on day 14.
Results: Highly monodisperse and stable AuNPs were synthesized successfully. Significant changes in the biochemical hemogram parameters were observed depending on the surface coatings of the AuNPs. PEI and PEG surface coatings increased biocompatibility. No excessive oxidative stress response was observed in all the gold nanoparticle groups.
Conclusions: It has been concluded that the surface chemistry of the particles is a more decisive parameter than the size in terms of in vivo biochemical toxicity. The surface functionalization, stability and biocompatibility of the AuNPs are important parameters for the potential biomedical applications of gold nanoparticles in future studies.
Sonodynamic therapy (SDT) triggered by ultrasound (US) has attracted increasing attention owing to its abilities to overcome critical limitations including low tissue‐penetration depth and ...phototoxicity in photodynamic therapy. Herein, the design of a new type of sonosensitizer is revealed, namely, ultrasmall oxygen‐deficient bimetallic oxide MnWOX nanoparticles, for multimodal imaging‐guided enhanced SDT against cancer. As‐made MnWOX nanoparticles with poly(ethylene glycol) (PEG) modification show high physiological stability and biocompatibility. Interestingly, such MnWOX‐PEG nanoparticles exhibit highly efficient US‐triggered production of 1O2 and •OH, higher than that of previously reported sonosensitizers (e.g., protoporphyrin IX and titanium dioxide), because the oxygen‐deficient structure of MnWOX serves as an electron trap site to prevent electron–hole recombination. The glutathione depletion capability of MnWOX‐PEG can also further favor SDT‐triggered cancer cell killing. With efficient tumor homing as illustrated by computer tomography and magnetic resonance imaging, MnWOX‐PEG enables effective destruction of mouse tumors under US stimulation. After accomplishing its therapeutic functions, MnWOX‐PEG can be metabolized by the mouse body without any long‐term toxicity. Herein, a new type of sono‐sensitizing agent with high SDT efficacy, multimodal imaging functions, and rapid clearance is presented, an agent which is promising for noninvasive SDT cancer treatment.
A new type of sonodynamic therapy (SDT) agent based on ultrasmall oxygen‐deficient bimetallic oxide MnWOX nanoparticles, which exhibit much higher sono‐sensitization efficiency compared with conventional SDT agents, as well as glutathione depletion capability to further favor SDT. Furthermore, their multimodal imaging functions and rapid renal clearance make them promising theranostic agents for imaging‐guided SDT.
Extensive research efforts have been devoted to the development of hydrogel microfibers for tissue engineering, because the vascular structure is related to the transport of nutrients and oxygen as ...well as the control of metabolic and mechanical functions in the human body. Even though stimuli-responsive properties would enhance the potential applicability of hydrogel microfibers for artificial tissue architectures, previous studies of their fabrication have not considered changes in the microfibers in response to external stimuli. In this work, we prepared temperature-responsive poly(
N
-isopropylacrylamide) (PNIPAm) microfibers with controlled shapes and sizes by the
in situ
photo-polymerization of aqueous monomers loaded in calcium alginate templates generated from microcapillary devices. We found that the shape and size of the hydrogel microfibers could be controlled by adjusting the injection positions of the solutions and varying the diameters of the inner capillary, respectively. We further fabricated light-responsive materials by incorporating photothermal magnetite nanoparticles (MNPs) within the temperature-responsive PNIPAm hydrogel microfibers. Because the MNPs incorporated into the PNIPAm microfibers generated heat upon the absorption of visible light, we could demonstrate volume changes in the microfibers triggered by both visible light irradiation and temperature.
Hydrogel microfibers containing magnetite nanoparticles prepared using a microfluidic device show a volume change in response to the visible light irradiation as well as increasing temperature.
Until now, poly(3,4-ethylenedioxythiophene):poly(styrensulfonate) (PEDOT:PSS) is widely used in Sn-Pb perovskite solar cells (PSCs) due to its many advantages, including high optical transparency, ...suitable conductivity, superior wettability, and so on. However, the acidic and hydroscopic properties of the PSS component, as well as the incongruous energy level of the hole transport layer (HTL), may lead to unsatisfying interface properties and decreased device performance. Herein, by adding polyethylene glycol dimethacrylate (PEGDMA) into PEDOT:PSS, a newly crosslinked-double-network obtain of PEDOT:PSS@PEGDMA film, which could not only optimize nucleation and crystallinity of Sn-Pb perovskite films, but also suppress defect density and optimize energy level alignment at the HTL/perovskite interface. As a result, the achieves highly efficient and stable mixed Sn-Pb PSCs with an encouraging power conversion efficiency of 20.9%. Additionally, the device can maintain good stability under N
atmosphere.
The application of nanoparticles (NPs) to drug delivery has led to the development of novel nanotherapeutics for the treatment of various diseases including cancer. However, clinical use of ...NP‐mediated drug delivery has not always translated into improved survival of cancer patients, in part due to the suboptimal properties of NP platforms, such as premature drug leakage during preparation, storage, or blood circulation, lack of active targeting to tumor tissue and cells, and poor tissue penetration. Herein, an innovative reactive oxygen species (ROS)‐responsive polyprodrug is reported that can self‐assemble into stable NPs with high drug loading. This new NP platform is composed of the following key components: (i) polyprodrug inner core that can respond to ROS for triggered release of intact therapeutic molecules, (ii) polyethylene glycol (PEG) outer shell to prolong blood circulation; and (iii) surface‐encoded internalizing RGD (iRGD) to enhance tumor targeting and tissue penetration. These targeted ROS‐responsive polyprodrug NPs show significant inhibition of tumor cell growth both in vitro and in vivo.
An innovative reactive oxygen species (ROS)‐responsive and tumor‐penetrating polyprodrug nanoplatform for targeted cancer therapy is developed. This nanoplatform can respond to intracellular ROS with a chain‐breakage patterned release of intact anticancer drug, leading to significant inhibition of tumor growth. This new platform can be of high interest for on‐demand delivery of other therapeutic drugs for effective cancer treatment.
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Colorectal cancer (CRC) is one of the most common and challenging malignancy that needs some effective and safer chemotherapeutic agents for the treatment. In this study, anticancer ...agent epirubicin (Epi) was loaded in polymeric polyethylene glycol-polylactic acid-nanoparticles (mPEG-PLA-NPs) coated with a marine anti-cancer non-toxic polysaccharide fucoidan (FC), to achieve a synergistic activity against CRC. The characterization of the NPs revealed that they were spherical, monodispersed, stable, with a negative zeta potential, and exhibited good biocompatibility and controlled release. In vitro anti-cancer activity of the NPs on HCT116 cell line was found to be promising, and corroborated well with in vivo studies involving BALB/C mice injected with C26 murine cancer cells. The outcome of MTT assay demonstrated that IC50 value of free Epi was 3.72 µM, and that of non-coated and coated Epi nano-formulations was 33.67 and 10.19 µM, respectively. Higher tumor regression, better survival and reduced off-side cardiotoxicity were observed when this novel NPs formulation was used to treat tumor-bearing mice. Free FC and Epi treated mice showed 37.73 % and 61.49 % regression in tumor size, whereas there was 79.76 % and 90.34 % tumor regression in mice treated with non-coated Epi NPs and coated Epi NPs, respectively. Therefore, mPEG-PLA-FC-Epi-NPs hold a potential to be used as an effective chemotherapeutic formulation against CRC, since it exhibited better efficacy and lower toxicity.
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