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.
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.
For successful cancer gene therapy via intravenous (i.v.) administration, it is essential to optimize the stability of carriers in the systemic circulation and the cellular association after the ...accumulation of the carrier in tumor tissue. However, a dilemma exists regarding the use of poly(ethylene glycol) (PEG), which is useful for conferring stability in the systemic circulation, but is undesirable for the cellular uptake and the following processes. We report the development of a PEG-peptide-lipid ternary conjugate (PEG-Peptide-DOPE conjugate (PPD)). In this strategy, the PEG is removed from the carriers via cleavage by a matrix metalloproteinase (MMP), which is specifically expressed in tumor tissues. An in vitro study revealed that the PPD-modified gene carrier (Multifunctional Envelope-type Nano Device: MEND) exhibited pDNA expression activity that was dependent on the MMP expression level in the host cells. In vivo studies further revealed that the PPD was potent in stabilizing MEND in the systemic circulation and facilitating tumor accumulation. Moreover, the i.v. administration of PPD or PEG/PPD dually-modified MEND resulted in the stimulation of pDNA expression in tumor tissue, as compared with a conventional PEG-modified MEND. Thus, MEND modified with PPD is a promising device, which has the potential to make in vivo cancer gene therapy achievable.
Abstract The need for bone repair has increased as the population ages. Stem cell-scaffold approaches hold immense promise for bone tissue engineering. However, currently, preformed scaffolds for ...cell delivery have drawbacks including the difficulty to seed cells deep into the scaffold, and inability for injection in minimally-invasive surgeries. Current injectable polymeric carriers and hydrogels are too weak for load-bearing orthopedic applications. The objective of this study was to develop an injectable and mechanically-strong stem cell construct for bone tissue engineering. Calcium phosphate cement (CPC) paste was combined with hydrogel microbeads encapsulating human umbilical cord mesenchymal stem cells (hUCMSCs). The hUCMSC-encapsulating composite paste was fully injectable under small injection forces. Cell viability after injection matched that in hydrogel without CPC and without injection. Mechanical properties of the construct matched the reported values of cancellous bone, and were much higher than previous injectable polymeric and hydrogel carriers. hUCMSCs in the injectable constructs osteodifferentiated, yielding high alkaline phosphatase, osteocalcin, collagen type I, and osterix gene expressions at 7 d, which were 50–70 fold higher than those at 1 d. Mineralization by the hUCMSCs at 14 d was 100-fold that at 1 d. In conclusion, a fully injectable, mechanically-strong, stem cell–CPC scaffold construct was developed. The encapsulated hUCMSCs remained viable, osteodifferentiated, and synthesized bone minerals. The new injectable stem cell construct with load-bearing capability may enhance bone regeneration in minimally-invasive and other orthopedic surgeries.
Hyaluronic acid-poly(ethylene glycol)-distearoyl phosphoethanolamine (HA-PEG-DSPE) modified and tocopheryl polyethylene glycol 1000 succinate (TPGS) contained nanostructured lipid carriers (NLCs) ...were prepared loading ropivacaine and dexmedetomidine to improve the topical anesthetic analgesic anesthesia efficiency.
NLCs were prepared by the solvent diffusion method. The average particle size, zeta potential, release behavior, and cytotoxicity of the NLCs were tested. Ex vivo skin permeation was studied using a Franz diffusion cell mounted with depilated rat skin. Local anesthesia antinociceptive efficiency was evaluated by rat tail flick latency study in vivo.
NLCs have sizes of about 100 nm, with negative zeta potentials. All the NLCs formulations were found to be significantly less cytotoxic than free drugs at equivalent concentrations. The cumulative amount of drugs penetrated through rat skin from NLCs was 2.0-4.7 folds higher than that of the drugs solution. The in vivo anesthesia antinociception study displayed that NLCs showed stronger and longer anesthesia antinociceptive effect when compared with single drugs loaded NLCs and drugs solution even at a lower dosage of drugs.
The results demonstrated that the HA modified, TPGS contained, dual drugs loaded NLCs could perform a synergistic effect and may reduce the amount of drugs, which can lower the toxicity of the system and at the meanwhile, increase the anesthesia antinociceptive efficiency.
Developing a gel polymer electrolyte (GPE) combining with superior mechanical strength and lithium-ion transportation properties is still a challenge. Herein, a new GPE based on polyethylene glycol ...(PEG) entrapped in cross-linked cellulose structure is prepared via one-step crosslinking method. The results showed that the composite gel membrane owned superior tensile strength from 33.92 MPa to 211.06 MPa and bending resistance when the content of PEG was changed from 2.5% to 20%. It exhibited considerable ionic conductivity of 3.31 × 10−3 S cm−1, together with an outstanding lithium-ion transfer number of 0.63 when the content of PEG was at 5%. The assembled Li/GPE/NCM523 batteries by this gel polymer electrolyte demonstrated initial discharge capacity of 159.3 mAh g−1 as well as the coulomb efficiency of 85.52% at 0.2C. Moreover, the as-prepared GPEs possessed good affinity with electrodes. Combing the high performance and optimized mechanical strength, we anticipate the possibility of this cost-effective and biodegradable GPE membranes applied in LIBs can be achieved.
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•A sustainable cellulose/PEG composite gel membrane was successfully prepared via one-step crosslinking method.•The GPE based on this composite membrane possessed excellent tensile strength and bending resistance.•The high electrolyte uptake, ionic conductivity and transport number were obtained.•The assembled cells showed good electrochemical performance.
Purpose: We evaluated the efficacy of Movicol® for treating children with chronic constipation.Methods: Children with chronic constipation treated with Movicol® between November 2018 and May 2019 ...were divided into two groups: the initial treatment group with no prior treatment for chronic constipation and the transitional group post-treated with magnesium oxide and/or sodium picosulfate. We retrospectively analyzed their profiles, availability of oral Movicol®, improvement in the number of defecations and stool form, and need for glycerin enema after treatment with Movicol® considering efficacy and side effects. We surveyed patient satisfaction using a questionnaire via telephone.Results: Of 36 children, eight were in the initial treatment treat and 28 in the transitional group; 33 children (91.7%) could take this medicine orally. The number of defecations increased in both groups, and stool form improved in the transitional group. Almost all children from both groups did not require enema. The efficacy of Movicol® for chronic constipation was confirmed in six children in the initial treatment group and 21 children in the transitional group 2–4 weeks after starting the treatment. It was also confirmed in five children in the initial treatment group and 25 children in the transitional group one and half to two years after starting treatment. Diarrhea was observed in one patient, but no severe side effects were observed. Thirty-three patients (91.7%) responded to the patient satisfaction questionnaire with an average satisfaction rating of 7.3 on a 10-point scale.Conclusion: Movicol® can be administered orally in children (91.7%), is effective in both groups, and can be the first treatment of choice.
Nanogels made of biomolecules are one of the potential candidates as a nanocarrier for drug delivery applications. The unique structural characteristics and excellent biocompatibility of DNA suggest ...that DNA nanogels would be an ideal candidate. Herein, a general design strategy for the crafting of DNA nanogels with controllable size using the multivalent host-guest interaction between β-CD functionalized branched DNA nanostructures as the host and a star-shaped adamantyl-terminated 8-arm poly(ethylene glycol) polymer as the guest is reported. Our results reveal that multivalent host-guest interactions are necessary for the nanogel formation. Nanogels exhibit excellent biocompatibility, good cell permeability and high drug encapsulation ability, which are promising features for their application as a drug carrier. The encapsulation of doxorubicin, an anticancer drug, inside the hydrophobic network of the nanogel and its delivery into cancer cells are also reported. We hope that the general design strategy demonstrated for the creation of DNA nanogels may encourage other researchers to use this approach for the design of DNA nanogels of other DNA nanostructures, and explore the potential of DNA nanogels in drug delivery applications.
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.
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The reconstruction of soft tissue, such as that which is found in the nervous system, is governed by the mechanical cues of the growth microenvironment. The complexity of the nervous ...system, particularly in cases of nerve repair and reconstruction, necessitates the development of facile high-throughput investigational tools. This study assesses the hypothesis that a mechanically tunable photoreactive interpenetrating network (IPN) of hyaluronic acid and Puramatrix can be manipulated in order to demonstrate that 3-D environmental stiffness influences neurite growth and proliferation. For these studies we employed photocrosslinkable glycidyl methacrylate hyaluronic acid (GMHA) and Puramatrix, a self-assembling peptide scaffold, leading to a structurally adjustable IPN system. Our in vitro model provides us with a simple, reproducible environment to generate different properties in a single specimen. Mechanically manipulated IPN systems with different degrees of methacrylation were fabricated using a dynamic mask projection photolithography apparatus and characterized. To gauge the impact of IPN stiffness on neurite outgrowth, dorsal root ganglia (DRG) explants were cultured in the hydrogels. We found that neurite outgrowth in 3-D was more likely to happen in an environment with a lesser degree of methacrylation, which corresponded to structures that were more compliant and more porous. Overall, tuning the mechanical behavior of our IPN systems led to statistically significant (p<0.05) differences in cellular growth and extension that warrants further investigations.
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