Novel magnetic fibrin hydrogel scaffolds containing thrombin and growth factors conjugated iron oxide nanoparticles for tissue engineering

Novel tissue-engineered magnetic fibrin hydrogel scaffolds were prepared by the interaction of thrombin-conjugated iron oxide magnetic nanoparticles with fibrinogen. In addition, stabilization of basal fibroblast growth factor (bFGF) was achieved by the covalent and physical conjugation of the growth factor to the magnetic nanoparticles. Adult nasal olfactory mucosa (NOM) cells were seeded in the transparent fibrin scaffolds in the absence or presence of the free or conjugated bFGF-iron oxide nanoparticles. The conjugated bFGF enhanced significantly the growth and differentiation of the NOM cells in the fibrin scaffolds, compared to the same or even five times higher concentration of the free bFGF. In the presence of the bFGF-conjugated magnetic nanoparticles, the cultured NOM cells proliferated and formed a three-dimensional interconnected network composed mainly of tapered bipolar cells. The magnetic properties of these matrices are due to the integration of the thrombin- and bFGF-conjugated magnetic nanoparticles within the scaffolds. The magnetic properties of these scaffolds may be used in future work for various applications, such as magnetic resonance visualization of the scaffolds after implantation and reloading the scaffolds via magnetic forces with bioactive agents, eg, growth factors bound to the iron oxide magnetic nanoparticles

Age-dependent effects of microglial inhibition in vivo on Alzheimer’s disease neuropathology using bioactive-conjugated iron oxide nanoparticles

Background: Tau dysfunction is believed to be the primary cause of neurodegenerative disorders referred to as tauopathies, including Alzheimer’s disease, Pick’s disease, frontotemporal dementia and Parkinsonism. The role of microglial cells in the pathogenesis of tauopathies is still unclear. The activation of microglial cells has been correlated with neuroprotective effects through the release of neurotrophic factors and through clearance of cell debris and phagocytosis of cells with intracellular inclusions. In contrast, microglial activation has also been linked with chronic neuroinflammation contributing to the development of neurodegenerative diseases such as tauopathies. Microglial activation has been recently reported to precede tangle formation and the attenuation of tau pathology occurs after immunosuppression of transgenic mice. Methods: Here we report the specific inhibition of microglial cells in rTg4510 tau-mutant mice by using fibrin γ377-395 peptide conjugated to iron oxide (γ-Fe2O3) nanoparticles of 21 ± 3.5 nm diameter. Results: Stabilization of the peptide by its covalent conjugation to the γ-Fe2O3 nanoparticles significantly decreased the number of the microglial cells compared to the same concentration of the free peptide. The specific microglial inhibition induces different effects on tau pathology in an age dependent manner. The reduction of activation of microglial cells at an early age increases the number of neurons with hyperphosphorylated tau in transgenic mice. In contrast, reduction of activation of microglial cells reduced the severity of the tau pathology in older mice. The number of neurons with hyperphosphorylated tau and the number of neurons with tangles are reduced than those in animals not receiving the fibrin γ377-395 peptide-nanoparticle conjugate. Conclusions: These results demonstrate a differential effect of microglial activity on tau pathology using the fibrin γ377-395 peptide-nanoparticle conjugate, depending on age and/or stage of the neuropathological accumulation and aggregation

Visual Field Endpoints Based on Subgroups of Points May Be Useful in Glaucoma Clinical Trials: A Study With the Humphrey Field Analyzer and Compass Perimeter

PRECIS: Visual field endpoints based on average deviation of specific subsets of points rather than all points may offer a more homogenous dataset without necessarily worsening test-retest variability and so may be useful in clinical trials. PURPOSE: To characterize outcome measures encompassing particular subsets of visual field points and compare them as obtained with Humphrey (HVF) and Compass perimeters. METHODS: 30 patients with imaging-based glaucomatous neuropathy performed a pair of 24-2 tests with each of 2 perimeters. Non-weighted mean deviation (MD) was calculated for the whole field and separate vertical hemifields, and again after censoring of points with low sensitivity (MDc) and subsequently including only "abnormal" points with total deviation probability of <5% (MDc5%) or <2% (MDc2%). Test-retest variability was assessed using Bland-Altman 95% limits of agreement (95%LoA). RESULTS: For the whole field, using HVF, MD was -7.5±6.9▒dB, MDc -3.6±2.8▒dB, MDc5% -6.4±1.7▒dB and MDc2% -7.3±1.5▒dB. With Compass MD was -7.5±6.6, MDc -2.9±1.7▒dB, MDc5% -6.3±1.5, and MDC2% -7.9±1.6. The respective 95% LoA were 5.5, 5.3, 4.6 and 5.6 with HVF, and 4.8, 3.7, 7.1 and 7.1 with Compass. The respective number of eligible points were 52, 42±12, 20±11 and 15±9 with HVF, and 52, 41.2±12.6, 10±7 and 7±5 with Compass. With both machines, standard deviation (SD) and 95%LoA increased in hemifields compared to the total field, but this increase was mitigated after censoring. CONCLUSIONS: Restricting analysis to particular subsets of points of interest in the visual field after censoring points with low sensitivity, as compared with using the familiar total field mean deviation, can provide outcome measures with a broader range of mean deviation, a markedly reduced SD and therefore more homogenous dataset, without necessarily worsening test-retest variability

Switchable Release of Entrapped Nanoparticles from Alginate Hydrogels

Natural biological processes are intricately controlled by the timing and spatial distribution of various cues. To mimic this precise level of control, the physical sizes of gold nanoparticles are utilized to sterically entrap them in hydrogel materials, where they are subsequently released only in response to ultrasound. These nanoparticles can transport bioactive factors to cells and direct cell behavior on‐demand

Sequential Release of Nanoparticle Payloads from Ultrasonically Burstable Capsules

In many biomedical contexts ranging from chemotherapy to tissue engineering, it is beneficial to sequentially present bioactive payloads. Explicit control over the timing and dose of these presentations is highly desirable. Here, we present a capsule-based delivery system capable of rapidly releasing multiple payloads in response to ultrasonic signals. In vitro, these alginate capsules exhibited excellent payload retention for up to 1 week when unstimulated and delivered their entire payloads when ultrasonically stimulated for 10–100 s. Shorter exposures (10 s) were required to trigger delivery from capsules embedded in hydrogels placed in a tissue model and did not result in tissue heating or death of encapsulated cells. Different types of capsules were tuned to rupture in response to different ultrasonic stimuli, thus permitting the sequential, on-demand delivery of nanoparticle payloads. As a proof of concept, gold nanoparticles were decorated with bone morphogenetic protein-2 to demonstrate the potential bioactivity of nanoparticle payloads. These nanoparticles were not cytotoxic and induced an osteogenic response in mouse mesenchymal stem cells. This system may enable researchers and physicians to remotely regulate the timing, dose, and sequence of drug delivery on-demand, with a wide range of clinical applications ranging from tissue engineering to cancer treatment

Rheological properties of magnetic biogels

We report an experimental and theoretical study of the rheological properties of magnetic biogels consisting of fibrin polymer networks with embedded magnetite nanoparticles, swollen by aqueous solutions. We studied two types of magnetic biogels, differenced by the presence or absence of an applied magnetic field during the initial steps of cross-linking. The experiments demonstrated very strong dependence of the elastic modulus of the magnetic biogels on the concentration of the magnetic particles. We finally developed some theoretical models that explain the observed strong concentration effects.This study was supported by projects FIS2013-41821-R (Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, MINECO, Spain, co-funded by ERDF, European Union) and FIS2017-85954-R (Ministerio de Economía, Industria y Competitividad, MINECO, andAgencia Estatal de Investigación, AEI, Spain, co-funded by Fondo Europeo de Desarrollo Regional, FEDER, European Union). A.Z. is grateful to the program of the Ministry of Education and Science of the Russian Federation, projects 02.A03.21.0006, 3.1438.2017/4.6, and 3.5214.2017/6.7, as well as to the Russian Fund of Basic Researches, project 18-08-00178