Enhancing Cell Seeding and Osteogenesis of MSCs on 3D Printed Scaffolds Through Injectable BMP2 Immobilized ECM-Mimetic Gel

Objective Design of bioactive scaffolds with osteogenic capacity is a central challenge in cell-based patient-specific bone tissue engineering. Efficient and spatially uniform seeding of (stem) cells onto such constructs is vital to attain functional tissues. Herein we developed heparin functionalized collagen gels supported by 3D printed bioceramic scaffolds, as bone extracellular matrix (ECM)-mimetic matrices. These matrices were designed to enhance cell seeding efficiency of mesenchymal stem cells (MSCs) as well as improve their osteogenic differentiation through immobilized bone morphogenic protein 2 (BMP2) to be used for personalized bone regeneration. Methods A 3D gel based on heparin-conjugated collagen matrix capable of immobilizing recombinant human bone morphogenic protein 2 (BMP2) was synthesized. Isolated dental pulp Mesenchymal stem cells (MSCs) were then encapsulated into the bone ECM microenvironment to efficiently and uniformly seed a bioactive ceramic-based scaffold fabricated using additive manufacturing technique. The designed 3D cell-laden constructs were comprehensively investigated trough in vitro assays and in vivo study. Results In-depth rheological characterizations of heparin-conjugated collagen gel revealed that elasticity of the matrix is significantly improved compared with freely incorporated heparin. Investigation of the MSCs laden collagen-heparin hydrogels revealed their capability to provide spatiotemporal bioavailability of BMP2 while suppressing the matrix contraction over time. The in vivo histology and real-time polymerase chain reaction (qPCR) analysis showed that the designed construct supported the osteogenic differentiation of MSCs and induced the ectopic bone formation in rat model. Significance The presented hybrid constructs combine bone ECM chemical cues with mechanical function providing an ideal 3D microenvironment for patient-specific bone tissue engineering and cell therapy applications. The implemented methodology in design of ECM-mimetic 3D matrix capable of immobilizing BMP2 to improve seeding efficiency of customized scaffolds can be exploited for other bioactive molecules

Microfluidic generation of cancer nanomedicines

Cancer diagnosis and therapy are perhaps the most promising areas for nanotechnology in medicine, and are expected to soon have applications in the market. The goal of this dissertation was to develop a technological foundation for synthesis and evaluation of polymer-based cancer therapeutic. This was performed using a microfluidic platform for optimization, and characterization of resulted particles for controlled drug release within the tumor environment. This technique was first optimized to show the feasibility of making drug-nanoparticles (NPs) out of different synthetic and natural polymers with it. The biophysical properties of these particles were also investigated at nano-biointerface. The process was then adjusted to develop pH-responsive core-shell NPs enabling oral administration of hydrophobic cancer therapeutics. This technique was also adjusted to fabricate complex NPs via controlled self-assembly of several components in a single step. Resulted particles can be used for theranostics applications or provide ultra-high drug loading capacity. Tuning the surface properties was also possible via this system and it was used to control immune-NPs and cancer cell-NPs interactions. To prolong blood circulation and enhance cell internalization, feasibility of making one-dimensional nanocarriers by template-based self-assembly approach was also confirmed. These nanocarriers can serve as suitable candidates for combinatorial cancer therapy as they can load and deliver substantial amounts of drugs while allowing for hyperthermia effect thanks to their carbon nanotube core. Mechanical properties of nanocarriers can also influence a broad range of NPs’ biological behaviors. Here, inspired by viruses, systematic investigation of the mechanobiological properties of NPs are done to determine the optimized range for in vitro and in vivo targeting. NPs with switchable mechanical properties are proposed capable of switching from soft to stiff state in the site of action and provide enhanced therapeutic efficiencies. Overall, we hope that this research provides broad information on how NP design can affect and control the efficacy of cancer nanomedicine. These findings point to the high potential of microfluidic platforms as engineering toolboxes that enable design of complex multifunctional nanomaterials via controlled bottom-up approach for various biomedical applications.Ph.D

Nano-in-Micro Dual Delivery Platform for Chronic Wound Healing Applications.

Here, we developed a combinatorial delivery platform for chronic wound healing applications. A microfluidic system was utilized to form a series of biopolymer-based microparticles with enhanced affinity to encapsulate and deliver vascular endothelial growth factor (VEGF). Presence of heparin into the structure can significantly increase the encapsulation efficiency up to 95% and lower the release rate of encapsulated VEGF. Our in vitro results demonstrated that sustained release of VEGF from microparticles can promote capillary network formation and sprouting of endothelial cells in 2D and 3D microenvironments. These engineered microparticles can also encapsulate antibiotic-loaded nanoparticles to offer a dual delivery system able to fight bacterial infection while promoting angiogenesis. We believe this highly tunable drug delivery platform can be used alone or in combination with other wound care products to improve the wound healing process and promote tissue regeneration

Nano-in-Micro Dual Delivery Platform for Chronic Wound Healing Applications.

Here, we developed a combinatorial delivery platform for chronic wound healing applications. A microfluidic system was utilized to form a series of biopolymer-based microparticles with enhanced affinity to encapsulate and deliver vascular endothelial growth factor (VEGF). Presence of heparin into the structure can significantly increase the encapsulation efficiency up to 95% and lower the release rate of encapsulated VEGF. Our in vitro results demonstrated that sustained release of VEGF from microparticles can promote capillary network formation and sprouting of endothelial cells in 2D and 3D microenvironments. These engineered microparticles can also encapsulate antibiotic-loaded nanoparticles to offer a dual delivery system able to fight bacterial infection while promoting angiogenesis. We believe this highly tunable drug delivery platform can be used alone or in combination with other wound care products to improve the wound healing process and promote tissue regeneration

Novel nanofiber-based triple-layer proton exchange membranes for fuel cell applications

New types of triple-layer membranes were fabricated using multi-step impregnation of Nation in electrospun webs based on bead-free nanofibers of sulfonated poly(ether sulfone) (SPES). The results showed that the fabricated nanofiber-filled membrane owing to its reduced methanol permeability as well as sufficient proton conductivity and membrane selectivity can be used as a promising proton exchange membrane for direct methanol fuel cell (DMFC) applications. The single cell DMFC performance results revealed that the SPES nanofiber-based triple-layer membranes have higher electrochemical performance than commercial Nation membranes. (C) 2011 Elsevier B.V. All rights reserved

Nanofiber-based polyelectrolytes as novel membranes for fuel cell applications

Partially sulfonated poly(ether sulfone) (SPES) was prepared and electrospun to bead-free nanofibers. The obtained data from solution conductivity measurements and scanning electron microscopy illustrated that sulfonation leads to a drastic increase in polymer solution conductivity and a considerable decrease in nanofiber diameter and a narrower diameter distribution. The new types of membranes were fabricated using Nafion-filled electrospun mats. The porous SPES nanofibrous membranes were impregnated with appropriate amount of Nafion solution. After a good pore-filling, an excess amount of Nafion solution was used to form a uniform top layer (SPES-N-N). Another bilayer polyelectrolyte membrane was prepared by direct electrospinning of SPES nanofibers on Nafion112 membrane's surface and followed by impregnation of Nafion solution into the pores of electrospun SPES (SPES-N-N112). The membranes were characterized by methanol permeability, proton conductivity, oxidative/hydrolytic stability as well as single cell direct methanol fuel cell (DMFC) performance tests. The proton to methanol selectivity of the SPES nanofiber-based bilayer membranes is about 53,680 and 45,500S s cm(-3) for SPES-N-N and SPES-N-N112 in comparison with 28,300 and 40,500S s cm(-3) for Nafion112 and Nafion117, respectively. The single cell DMFC performance results revealed that the SPES nanofiber-based-bilayer membranes have higher electrochemical performance than Nafion112 and Nafion117 membranes especially in elevated methanol concentration. The results showed that the fabricated bilayer membranes can be used as a promising polyelectrolyte membrane for fuel cell applications (C) 2010 Elsevier B.V. All rights reserved

Molecular dynamics simulation study of proton diffusion in polymer electrolyte membranes based on sulfonated poly (ether ether ketone)

Molecular dynamics (MD) simulation technique was employed to investigate the effect of degree of sulfonation (DS) on structural and dynamical characteristics of sulfonated poly (ether ether ketone) (SPEEK) membranes at different temperatures. MD Simulations were performed for the cell containing SPEEK chains, hydronium ions and water molecules under NVT and NPT conditions. By evaluating the pair correlation functions, it was observed that with increasing the DS of SPEEK, the distance between sulfur atoms increases, more water molecules solvate the sulfur atoms and hydronium ions, the average sulfur hydronium ion separation distance increases and larger water clusters are formed. It was also found that with increasing DS and temperature, the diffusion coefficient and conductivity of hydronium ions enhance. It was also understood, the simulated ionic conductivities qualitatively follow the experimental data. Copyright (C) 2012, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved

Organically modified montmorillonite and chitosan-phosphotungstic acid complex nanocomposites as high performance membranes for fuel cell applications

Nanocomposite membranes based on polyelectrolyte complex (PEC) of chitosan/phosphotungstic acid (PWA) and different types of montmorillonite (MMT) were prepared as alternative membranes to Nafion for direct methanol fuel cell (DMFC) applications. Fourier transform infrared spectroscopy (FTIR) revealed an electrostatically fixed PWA within the PEC membranes, which avoids a decrease in proton conductivity at practical condition. Various amounts of pristine as well as organically modified MMT (OMMT) (MMT: Cloisite Na, OMMT: Cloisite 15A, and Cloisite 30B) were introduced to the PEC membranes to decrease in methanol permeability and, thus, enhance efficiency and power density of the cells. X-ray diffraction patterns of the nanocomposite membranes proved that MMT (or OMMT) layers were exfoliated in the membranes at loading weights of lower than 3 wt.%. Moreover, the proton conductivity and the methanol permeability as well as the water uptake behavior of the manufactured nanocomposite membranes were studied. According to the selectivity parameter, ratio of proton conductivity to methanol permeability, the PEC/2 wt.% MMT 30B was identified as the optimum composition. The DMFC performance tests were carried out at 70 A degrees C and 5 M methanol feed and the optimum membrane showed higher maximum power density as well as acceptable durability compared to Nafion 117. The obtained results indicated that owing to the relatively high selectivity and power density, the optimum nanocomposite membrane could be considered as a promising polyelectrolyte membrane (PEM) for DMFC applications

Prepration and Characterization of Novel Ionoic Polymers to beUsed as Artificial Muscles: Novel ionic polymers for artificial muscles

The muscle-like technology would be of enormous advantages for biomedical applications such as medical implants and human assist devices. Ionic polymer metal composites (IPMCs) are one kind of biomimetic actuators. An ionic polymer metal composite composed from an ionomer with high ion exchange capacity that packed between two thin metal layers. In the present study we focused on the preparation of a novel alternative polymeric ionomer to be used as artificial muscles. Sulfonated poly(ether ether ketone) (PEEK) have been synthesized as a new class of ionomeric membrane materials. PEEK was sulfonated at various degrees with sulfuric acid and N,N-Dimethylacetamide as a solvent. Fourier transfer infrared spectroscopy confirmed the quality of substitution reaction. Sulfonated samples showed O-H vibration at 3490 and S=O peaks at 1085 and 1100-1300 cm-1. By increasing degree of sulfonation to 80%, ion exchange capacity, water uptake and the number of water molecules per the fixed sulfone groups (λ) were increased to about 2.4 meq.g-1, 75% and 19, respectively. After calculating the optimum degree of sulfonation, the applications of these ionomers as actuators are studied. Rigid microstructure of PEEK backbone causes to slow displacement. However, this inflexible backbone showed the acceptable tip force during its actuation. These IPMC are easy to prepare and much less expensive than the commercial per-fluorinated membranes such as Nafion®. The results approve the utilization of sulfonated aromatic for artificial muscles applications as novel strong muscles with low flexibility