- Injectable and self-healing polysaccharide-based hydrogel for pH-responsive drug release. [Journal Article]
- IJInt J Biol Macromol 2018 Nov 09
- Injectable hydrogels with self-healing and pH-responsive property are appealing for biomedical applications. Herein, we developed a facile and green method to prepare a multifunctional polysaccharide...
Injectable hydrogels with self-healing and pH-responsive property are appealing for biomedical applications. Herein, we developed a facile and green method to prepare a multifunctional polysaccharide-based hydrogel as a new carrier of drug. The hydrogels were prepared by forming reversible chemical bond between carboxyethyl-modified chitosan (CEC) and aldehyde modified hyaluronic acid (A-HA). The morphology and rheological property of the hydrogels with different solid content were systematically characterized. Owing to the dynamic equilibrium of the Schiff base bonds between amine groups on CEC and aldehyde groups on A-HA, the rapid self-healing performance of hydrogels was confirmed through qualitative and quantitative methods without any external stimulus. The pH-responsive behaviour was demonstrated by equilibrium swelling and in vitro Doxorubicin (Dox) release in PBS medium with various pH. In acidic condition, Dox can be release more rapidly compared with weak alkaline medium. Furthermore, the kill effect of Dox released from hydrogels for cancer cells was investigated. In vitro degradation and cytotoxicity examinations showed that the hydrogel is biodegradable and biocompatible. Therefore, such polysaccharide-based injectable self-healing and pH-responsive hydrogel is a promising candidate as drug delivery carrier.
- Durability of Diabetic Retinopathy Improvement with As-Needed Ranibizumab: Open-label Extension of RIDE and RISE Studies. [Journal Article]
- OOphthalmology 2018 Nov 09
- CONCLUSIONS: DR severity improvements with ranibizumab were maintained in the majority of patients in the OLE after switching from ranibizumab monthly to an individualized best-corrected visual acuity- and optical coherence tomography-based ranibizumab 0.5 mg PRN dosing regimen. Because nearly one-third of OLE patients not requiring further therapy for DME experienced DR worsening, once DME resolves, patients should be watched carefully for worsening of DR and possible need for more frequent follow-up and/or treatment of vision-threatening disease with anti-VEGF or other modalities.
- Hydrazone covalent adaptable networks modulate extracellular matrix deposition for cartilage tissue engineering. [Journal Article]
- ABActa Biomater 2018 Nov 09
- Cartilage tissue engineering strategies often rely on hydrogels with fixed covalent crosslinks for chondrocyte encapsulation; yet the resulting material properties are largely elastic and can impede ...
Cartilage tissue engineering strategies often rely on hydrogels with fixed covalent crosslinks for chondrocyte encapsulation; yet the resulting material properties are largely elastic and can impede matrix deposition. To address this limitation, hydrazone crosslinked poly(ethylene glycol) hydrogels were formulated to achieve tunable viscoelastic properties and to study how chondrocyte proliferation and matrix deposition vary with the time-dependent material properties of covalent adaptable networks. Hydrazone equilibrium differences were leveraged to produce average stress relaxation times from hours (4.01x103s) to months (2.78x106s) by varying the percentage of alkyl-hydrazone (aHz) to benzyl-hydrazone (bHz) crosslinks. Swelling behavior and degradation associated with adaptability was characterized to quantify temporal network changes that can influence the behavior of encapsulated chondrocytes. After four weeks, mass swelling ratios varied from 36±3 to 17±0.4 and polymer retention ranged from 46±4% to 92±5%, with higher aHz content leading to loss of network connectivity with time. Hydrogels were formulated near the Flory-Stockmayer bHz percolation threshold (17% bHz) to investigate chondrocyte response to distinct levels of covalent architecture adaptability. Four weeks post-encapsulation, formulations with average relaxation times of 3 days (2.6x105s) revealed increased cellularity and an interconnected articular cartilage-specific matrix. Chondrocytes embedded in this adaptable formulation (22% bHz) deposited 190±30% more collagen and 140±20% more sulfated glycosaminoglycans compared to the 100% bHz control, which constrained matrix deposition to pericellular space. Collectively, these findings indicate that incorporating highly adaptable aHz crosslinks enhanced regenerative outcomes. However, connected networks containing more stable bHz bonds were required to achieve the highest quality neocartilaginous tissue. STATEMENT OF SIGNIFICANCE: Covalently crosslinked hydrogels provide robust mechanical support for cartilage tissue engineering applications in articulating joints. However, these materials traditionally demonstrate purely elastic responses to deformation despite the dynamic viscoelastic properties of native cartilage tissue. Here, we present hydrazone poly(ethylene glycol) hydrogels with tunable viscoelastic properties and study covalent adaptable networks for cartilage tissue engineering. Using hydrazone equilibrium and Flory-Stockmayer theory we identified average relaxation times leading to enhanced regenerative outcomes and showed that extracellular matrix deposition was biphasic as a function of the hydrazone covalent adaptability. We also showed that the incorporation of highly adaptable covalent crosslinks could improve cellularity of neotissue, but that a percolating network of more stable bonds was required to maintain scaffold integrity and form the highest quality neocartilaginous tissue.
- Effect of Platelet-Rich Plasma Injection for Rejuvenation of Photoaged Facial Skin: A Randomized Clinical Trial. [Journal Article]
- JDJAMA Dermatol 2018 Nov 07
- CONCLUSIONS: Masked participants noted that both fine and coarse texture improved significantly more with a single treatment of PRP than with normal saline. Both participants and raters found PRP to be nominally but not significantly superior to normal saline.
- Severe Nasal Swelling. [Journal Article]
- JOJAMA Otolaryngol Head Neck Surg 2018 Nov 08
- Altered function of the glutamate-aspartate transporter GLAST, a potential therapeutic target in glioblastoma. [Journal Article]
- IJInt J Cancer 2018 Nov 12
- In glioma patients, high levels of glutamate can cause brain edema and seizures. GLAST, a glutamate-aspartate transporter expressed by astrocytes with a role in glutamate uptake, is highly expressed ...
In glioma patients, high levels of glutamate can cause brain edema and seizures. GLAST, a glutamate-aspartate transporter expressed by astrocytes with a role in glutamate uptake, is highly expressed on the plasma membrane of glioblastoma (GBM) cells, and its expression significantly correlates with shortened patient survival. Here, it was demonstrated that inhibition of GLAST expression limited the progression and invasion of GBM xenografts. Magnetic resonance spectroscopy was used to measure glutamate in GLAST-expressing gliomas showing that these tumors exhibit increased glutamate concentration compared to GLAST-depleted glioma. Despite their GLAST expression, GBM stem-like cells (GSCs) released rather than taking up glutamate due to their lack of Na+/K+-ATPase. Overexpression of Na+/K+-ATPase in these cells restored glutamate uptake and induced apoptosis. The therapeutic relevance of targeting GLAST in gliomas was assessed using the inhibitor UCPH-101. In glioma-bearing mice, a single intratumoral injection of UCPH-101 significantly increased survival by decreasing GLAST expression and inducing apoptosis. Thus, GLAST has a novel role in GBM that appears to have crucial relevance in glutamate trafficking and may thus be a new therapeutic target. This article is protected by copyright. All rights reserved.
- Membrane nanotube pearling restricted by confined polymers. [Journal Article]
- SMSoft Matter 2018 Nov 12
- Increasing evidence showed that membrane nanotubes readily undergo pearling in response to external stimuli, while long tubular membrane structures have been observed connecting cells and functioning...
Increasing evidence showed that membrane nanotubes readily undergo pearling in response to external stimuli, while long tubular membrane structures have been observed connecting cells and functioning as channels for intercellular transport, raising a fundamental question of how the stability of membrane nanotubes is maintained in the cellular environment. Here, combining dissipative particle dynamics simulations, free energy calculations, and a force analysis, we propose and demonstrate that nanotube pearling can be restricted by confined polymers, which can be DNA and protein chains transported through the nanotubes, or actin filaments participating in tube formation and elongation. Thermodynamically, nanotube pearling releases the membrane surface energy, but costs bending energies of both the membrane and the confined polymers. Following the mechanism, the pearling of nanotubes confining longer and stiffer polymers is more difficult as it costs larger polymer bending energies. In dynamics, nanotube pearling occurs by repelling polymers from the region of nanotube shrinking to that of swelling. Shorter polymers can be readily repelled owing to the unbalanced force exerted by the shrinking tube region, whereas longer polymers tend to be trapped at the shrinking region to retard the nanotube pearling. Besides the low surface tension maintained by lipid reservoirs kept in living cells, our results supplement the explanation for the stability of membrane nanotubes, and open up a new avenue to manipulate the shape deformation of tubular membrane structures for study of many biological processes.
- Eculizumab Is Safe and Effective as a Long-term Treatment for Protein-losing Enteropathy Due to CD55 Deficiency. [Journal Article]
- JPJ Pediatr Gastroenterol Nutr 2018 Nov 08
- CONCLUSIONS: CD55-deficiency patients present with early-onset diarrhea, edema, severe hypoalbuminemia, abdominal pain, and malnutrition. Targeted therapy with the terminal complement inhibitor eculizumab has positive clinical and laboratory outcomes in PLE related to CD55 loss-of-function mutations, previously a life-threatening condition. Our results demonstrate the potential of genetic diagnosis to guide tailored treatment, and underscore the significant role of the complement system in the intestine.
- OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY CHANGES AFTER SUBTHRESHOLD MICROPULSE YELLOW LASER IN DIABETIC MACULAR EDEMA. [Journal Article]
- RRetina 2018 Nov 07
- CONCLUSIONS: Subthreshold micropulse yellow laser induces more pronounced changes in the DCP than in the SCP in DME. These changes occurred as early as 3 months after treatment. The evaluation of specific parameters in the DCP may help in determining treatment response.
New Search Next
- Therapeutic Efficacy of Home-Use Photobiomodulation Devices: A Systematic Literature Review. [Journal Article]
- PLPhotomed Laser Surg 2018 Nov 10
- CONCLUSIONS: Home-use PBM devices appear to mediate effective, safe treatments in a variety of conditions that require frequent applications. Conclusive evaluation of their efficacy requires additional, randomized controlled studies.