Nanoengineered Biomaterials for Cell and Therapeutic Delivery

Direct-write extrusion bioprinting, a form of additive manufacturing, is a useful technique to recapitulate anatomical complexity for tissue engineering applications. However, bioprinting has hit a bottleneck in progress due to the lack of available bioinks with high printability, mechanical strength, and biocompatibility. Here, we report a family of hydrogel-based bioinks for extrusion bioprinting from poly (ethylene glycol) (PEG) and two-dimensional (2D) nanoparticles. PEG, a non-fouling easily modifiable polymer, combined with biocompatible Laponite XLG nanoparticles (2D nanosilicates) to obtain shear-thinning hydrogel bioinks. Electrostatic interactions between nanoparticles and hydrogen-bonding between polymer and nanoparticles govern the flow behavior and printability of bioink. The evaluation of hydrogel bioink using flow sweeps, peak holds, and dynamic oscillatory rheology, suggest that minimum shear-thinning index of ~0.3, solution viscosities >1000 Pa·s, and 80% recovery within 30s are necessary for printing high fidelity constructs. Mechanically stiff 3D printed structures are obtained by covalently crosslinking polymeric chains using ultraviolet (UV) light. Modifications to the PEG system through inclusion of dithiothreitol linkage or combining with gelatin methacrylate are used to control matrix degradation, cell adhesion properties, and therapeutic release. We envision that PEG bioinks can be used to print complex, large-scale, cell-laden tissue constructs with high structural fidelity and mechanical stiffness for applications in custom bioprinted scaffolds and tissue engineered implants

Nanoengineered Biomaterials for Cell and Therapeutic Delivery

Direct-write extrusion bioprinting, a form of additive manufacturing, is a useful technique to recapitulate anatomical complexity for tissue engineering applications. However, bioprinting has hit a bottleneck in progress due to the lack of available bioinks with high printability, mechanical strength, and biocompatibility. Here, we report a family of hydrogel-based bioinks for extrusion bioprinting from poly (ethylene glycol) (PEG) and two-dimensional (2D) nanoparticles. PEG, a non-fouling easily modifiable polymer, combined with biocompatible Laponite XLG nanoparticles (2D nanosilicates) to obtain shear-thinning hydrogel bioinks. Electrostatic interactions between nanoparticles and hydrogen-bonding between polymer and nanoparticles govern the flow behavior and printability of bioink. The evaluation of hydrogel bioink using flow sweeps, peak holds, and dynamic oscillatory rheology, suggest that minimum shear-thinning index of ~0.3, solution viscosities >1000 Pa·s, and 80% recovery within 30s are necessary for printing high fidelity constructs. Mechanically stiff 3D printed structures are obtained by covalently crosslinking polymeric chains using ultraviolet (UV) light. Modifications to the PEG system through inclusion of dithiothreitol linkage or combining with gelatin methacrylate are used to control matrix degradation, cell adhesion properties, and therapeutic release. We envision that PEG bioinks can be used to print complex, large-scale, cell-laden tissue constructs with high structural fidelity and mechanical stiffness for applications in custom bioprinted scaffolds and tissue engineered implants

National security, Islamophobia, and religious freedom in the U.S.

A central argument in Hurd’s (2015) Beyond Religious Freedom is that the religious freedom policy framework pursued by the United States not only entrenches lines of division between religious faiths, but also is constructive of those very divisions. Where foreign and domestic policies purport to promote tolerance and respectful pluralism in the name of religious freedom, Hurd (2015, 41) contends they instead create ‘new forms of social friction defined by religious difference.’ Utilizing Hurd’s (2015) categories of Official, Governed, and Lived religion I examine Islamophobia and the racialization of Muslims in the United States and demonstrate how over-identification with religious groups can exacerbate social tensions; how the ‘agenda of surveillance’ (Hurd 2015) disproportionately targets Muslims in the United States; and argue that recourse to law and policy alone in response to anti-Muslim discrimination is unlikely to transform social attitudes towards Muslims. Finally, I utilize a contemporary reworking of Adam Smith’s sympathetic imagination and radical democratic theory to propose an alternative pathway towards dissolving the pejorative ascription of difference to religiously othered individuals

The Physics of the B Factories

This work is on the Physics of the B Factories. Part A of this book contains a brief description of the SLAC and KEK B Factories as well as their detectors, BaBar and Belle, and data taking related issues. Part B discusses tools and methods used by the experiments in order to obtain results. The results themselves can be found in Part C

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Robust and Degradable Hydrogels from Poly(ethylene glycol) and Semi-Interpenetrating Collagen

Poly­(ethylene glycol) (PEG) and interpenetrating collagen can be used to synthesize hydrogels that are elastomeric-like, can withstand reversible loadings, degrade, and are bioactive. Here we present the synthesis of a hydrogel system made of PEG modified with lactide and acrylate end groups and then photo cross-linked in the presence of type I collagen. The hydrogel precursor solutions are low viscous and the cross-linked hydrogels form elastomeric-like polymer networks. Mechanical properties of the hydrogels were found to depend predominantly on PEG concentration and less on collagen. This is possibly due to a balance of molecular interactions that reinforce and weaken the network structure. Hydrogel degradation times were strongly dependent on temperature. The experimental results from this project show how to generate robust, and degradable hydrogels containing bioactive collagen. The data show promise and show the versatility of making biotechnologically relevant soft materials from a few components

Nanoengineered Colloidal Inks for 3D Bioprinting

Nanoengineered hydrogels offer the potential to design shear-thinning bioinks for three-dimensional (3D) bioprinting. Here, we have synthesized colloidal bioinks composed of disk-shaped two-dimensional (2D) nanosilicates (Laponite) and poly­(ethylene glycol) (PEG). The addition of Laponite reinforces the PEG network and increases viscosity, storage modulus, and network stability. PEG-Laponite hydrogels display shear-thinning and self-recovery characteristics due to rapid internal phase rearrangement. As a result, a range of complex patterns can be printed using PEG-Laponite bioinks. The 3D bioprinted structure has similar mechanical properties compared to the as-casted structure. In addition, encapsulated cells within the PEG-Laponite bioink show high viability after bioprinting. Overall, this study introduces a new class of PEG-Laponite colloidal inks for bioprinting and cell delivery