Modulating immune response inside biomaterial-based nerve conduits to stimulate endogenous peripheral nerve regeneration

Injuries to the peripheral nervous system (PNS) are major and common source of disability, impairing the ability to move muscles and/or feel normal sensations, or resulting in painful neuropathies. Annually traumatic nerve injuries resulting from collisions, gunshot wounds, fractures, motor vehicle accidents, lacerations, and other forms of penetrating trauma, affected more than 250,000 patients just in the U.S. The clinical gold standard to bridge long non-healing nerve gaps is to use a nerve autograft- typically the patient’s own sural nerve. However, autografts are not ideal because of the need for secondary surgery to ‘source’ the nerve, loss of function at the donor site, lack of appropriate source nerve in diabetic patients, neuroma formation, and the need for multiple graft segments. Despite our best efforts, finding alternative ‘nerve bridges’ for peripheral nerve repair remains challenging – of the four nerve ‘tubes’ FDA approved for use in the clinic, none is typically used to bridge gaps longer than 10 mm due to poor outcomes. Hence, there is a compelling need to design alternatives that match or exceed the performance of autografts across critically sized nerve gaps. Here we demonstrate that early modulation of innate immune response at the site of peripheral nerve injury inside biomaterials-based conduit can favorably bias the endogenous regenerative potential after injury that obviates the need for the downstream modulation of multiple factors and has significant implications for the treatment of long peripheral nerve gaps. Moreover, our study strongly suggests that more than the extent of macrophage presence, their specific phenotype at the site of injury influence the regenerative outcomes. This research will advance our knowledge regarding peripheral nerve regeneration, and help developing technologies that are likely to improve clinical outcomes after peripheral nerve injury. The significant results presented here are complementary to a growing body of evidence showing the direct correlation between macrophage phenotype and the regeneration outcome of injured tissues.Ph.D

Preparation and characterization of nanocomposite polyelectrolyte membranes based on Nafion (R) ionomer and nanocrystalline hydroxyapatite

In this study nanocrystalline hydroxyapatite (nHA) was synthesized and characterized by means of FT-IR, XRD and TEM techniques and a series of proton exchange membranes based on Nafion (R) and nHA were fabricated via solvent casting method. Thermogravimetric analysis confirmed thermal stability enhancement of the Nafion (R) nanocomposite due to the presence of nHA nanopowder. SAXS and TEM analyses confirmed the incorporation of nHA into ionic phase of Nafion (R). Furthermore, the incorporation of elliptical nHA into the Nafion (R) matrix improved proton conductivity of the resultant polyelectrolyte membrane up to 0.173 S cm(-1) at 2.0 wt% of nHA loading compared to that of 0.086 S cm(-1) for Nafion (R) 117. Also, the inclusion of nHA nanoparticles into nanocomposite membranes resulted in a significant reduction of methanol permeability and crossover in comparison with pristine Nafion (R) membranes. Membrane selectivity parameter of the nanocomposites at 2.0 wt% nHA was calculated and found to be 106,800 S s cm(-3), which is more than two times than that of Nafion (R) 117. Direct methanol fuel cell tests revealed that Nafion (R)/nHA nanocomposite membranes were able to provide higher fuel cell efficiency and also better electrochemical performance in both low and high concentrations of methanol feed. Thus, the current study shows that nHA enhances the functionality of Nafion (R) as fuel cell membranes. (C) 2010 Elsevier Ltd. All rights reserved

A microfluidic approach to synthesizing high-performance microfibers with tunable anhydrous proton conductivity

Here, we demonstrate a new approach for the synthesis of ion exchange microfibers with finely tuned anhydrous conductivity. This work presents microfluidics as a system to control the size and phosphoric acid (PA) doping level of the polybenzimidazole (PBI) microfibers. It has been shown that the PA doping level can be controlled by varying the flow ratios in the microfluidic channel. The diameter of the microfibers increased with extending mixing time, whereas the doping level decreased with increasing flow ratio. The highest doping level, 16, was achieved at the flow ratio of 0.175. The anhydrous proton conductivity of the microfibers was found to be adjustable between 0.01 and 0.1 S cm(-1) at 160 degrees C, which is considerably higher than for conventionally doped PBI cast membranes (0.004 S cm(-1)). Furthermore, molecular dynamic simulation of proton conduction through the microfibers at different doping levels was in good agreement with the experimental results. These results demonstrate the potential of the microfluidic technique to precisely tune the physicochemical properties of PBI microfibers for various electrochemical applications such as hydrogen sensors, fuel cells as well as artificial muscles

On-Chip Fabrication of Paclitaxel-Loaded Chitosan Nanoparticles for Cancer Therapeutics

The use of solvent-free microfluidics to fine-tune the physical and chemical properties of chitosan nanoparticles for drug delivery is demonstrated. Nanoparticle self-assembly is driven by pH changes in a water environment, which increases biocompatibility by avoiding organic solvent contamination common with traditional techniques. Controlling the time of mixing (2.5–75 ms) during nanoparticle self-assembly enables us to adjust nanoparticle size and surface potential in order to maximize cellular uptake, which in turn dramatically increases drug effectiveness. The compact nanostructure of these nanoparticles preserves drug potency better than previous nanoparticles, and is more stable during long-term circulation at physiological pH. However, when the nanoparticles encounter a tumor cell and the associated drop in pH, the drug contents are released. Moreover, the loading efficiency of hydrophobic drugs into the nanoparticles increases significantly from previous work to over 95%. The microfluidic techniques used here have applications not just for drug-carrying nanoparticle fabrication, but also for the better control of virtually any self-assembly process