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Editorial: Fractal Engineering and Biomedicine

J. Nanotechnol. Eng. Med. 2016;6(4):040201-040201-3. doi:10.1115/1.4033099.
Commentary by Dr. Valentin Fuster

Guest Editorial: Engineering Cell Microenvironment using Novel Hydrogels

J. Nanotechnol. Eng. Med. 2016;6(4):040301-040301-2. doi:10.1115/1.4033192.

This prelude to Engineering of Cell Microenvironment Using Novel focuses on reporting recent advances and trends in the development of functional hydrogel systems to engineer cell microenvironment for various emerging applications, such as biomanipulation, tissue engineering, and regenerative medicine. Typically, hydrogel systems are network of macromolecular polymers crosslinked through physical or covalent bonds. The unique three-dimensional (3D) net structure endows hydrogels with highly absorbent ability and flexible mechanical properties. These characteristic properties of hydrogels offer them with biomimicking properties to natural extracellular matrix (ECM) in vitro, especially useful for biomedical and pharmaceutical applications. In recent years, novel hydrogel systems with extra structural features, functionalities, or properties have gained increasing attentions and exhibited significant impact for biological, biomedical, and pharmaceutical applications. Such state-of-the-art hydrogel systems can be hybrid, nano/microstructure patterned, multifunctional, and responsive. These add-on features of the functional hydrogels enable the precise manipulation of cell biological, physical, mechanical, and electrical microenvironment in vitro, demonstrating to be ideal model systems to direct dynamic tissue regeneration and to study basic cell biological behaviors.

Topics: Hydrogels
Commentary by Dr. Valentin Fuster

Review Articles: Engineering Cell Microenvironment Using Novel Hydrogels

J. Nanotechnol. Eng. Med. 2016;6(4):040801-040801-10. doi:10.1115/1.4033193.

The rapid progress of embryonic stem cell (ESCs) research offers great promise for drug discovery, tissue engineering, and regenerative medicine. However, a major limitation in translation of ESCs technology to pharmaceutical and clinical applications is how to induce their differentiation into tailored lineage commitment with satisfactory efficiency. Many studies indicate that this lineage commitment is precisely controlled by the ESC microenvironment in vivo. Engineering and biomaterial-based approaches to recreate a biomimetic cellular microenvironment provide valuable strategies for directing ESCs differentiation to specific lineages in vitro. In this review, we summarize and examine the recent advances in application of engineering and biomaterial-based approaches to control ESC differentiation. We focus on physical strategies (e.g., geometrical constraint, mechanical stimulation, extracellular matrix (ECM) stiffness, and topography) and biochemical approaches (e.g., genetic engineering, soluble bioactive factors, coculture, and synthetic small molecules), and highlight the three-dimensional (3D) hydrogel-based microenvironment for directed ESC differentiation. Finally, future perspectives in ESCs engineering are provided for the subsequent advancement of this promising research direction.

Commentary by Dr. Valentin Fuster
J. Nanotechnol. Eng. Med. 2016;6(4):040802-040802-6. doi:10.1115/1.4032832.

Being a natural polymer, DNA attracts extensive attention and possesses great potential to open a new way for researches of biomedical or material science. In the past few decades, approaches have been developed to bring DNA into the realm of bulk materials. In this review, we discussed the progresses achieved for fabrication of novel materials with a large physical dimension from the DNA polymer.

Topics: Bulk solids , DNA , Hydrogels
Commentary by Dr. Valentin Fuster

Research Papers: Engineering Cell Microenvironment Using Novel Hydrogels

J. Nanotechnol. Eng. Med. 2016;6(4):041001-041001-6. doi:10.1115/1.4032902.

To promote bone regeneration in vivo using critical-size calvarial defect model, hybrid hydrogel was prepared by mixing chitosan with hydroxyapatite (HA) and ultraviolet (UV) irradiation in situ. The hydrosoluble, UV-crosslinkable and injectable N-methacryloyl chitosan (N-MAC) was synthesized via single-step N-acylation reaction. The chemical structure was confirmed by 1H-NMR and FTIR spectroscopy. N-MAC hydrogel presented a microporous structure with pore sizes ranging from 10 to 60 μm. Approximately 80% cell viability of N-MAC hydrogel against encapsulated 3T3 cell indicated that N-MAC is an emerging candidate for mimicking native extracellular matrix (ECM). N-MAC hydrogel hybridized with HA was used to accelerate regeneration of calvarial bone using rabbit model. The effects of hybrid hydrogels to promote bone regeneration were evaluated using critical size calvarial bone defect model. The healing effects of injectable hydrogels with/without HA for bone regeneration were investigated by analyzing X-ray image after 4 or 6 weeks. The results showed that the regenerated new bone for N-MAC 100 was significantly greater than N-MAC without HA and untreated controls. The higher HA content in N-MAC/HA hybrid hydrogel benefited the acceleration of bone regeneration. About 50% closure of defect site after 6 weeks postimplantation demonstrated potent osteoinductivity of N-MAC 100 UV-crosslinkable and injectable N-MAC/HA hybrid hydrogel would allow serving as a promising biomaterial for bone regeneration using the critical-size calvarial defect.

Commentary by Dr. Valentin Fuster
J. Nanotechnol. Eng. Med. 2016;6(4):041002-041002-6. doi:10.1115/1.4032903.

Three-dimensional (3D) in vivo cell culture modeling is quickly emerging as a platform to replace two-dimensional (2D) monolayer cell culture in vitro tests. Three-dimensional tumor models mimic physiological conditions and provide valuable insight of the tumor cell response to drug discovery application. In this study, we used poly(ethylene glycol) (PEG) hydrogel microwells to generate 3D brain cancer spheroids and studied their treatment with anticancer drugs in single or combination treatment. Glioblastoma (GBM) spheroids were grown through 14 days before infecting with two drugs: Pitavastatin and Irinotecan at various concentrations. A significant cell lysis was observed and cell viability decreased to lower than 7% when drugs were combined at the concentration Pitavastatin 10 μM and Irinotecan 50 μM to infect after 7 days. These findings demonstrate a promising platform—PEG hydrogel microwells—that should be an efficient way to test the drug sensitivity in vitro as well as application in different studies.

Commentary by Dr. Valentin Fuster

Research Papers: Computational Modeling of Polymer-Matrix Composites at Different Length Scales

J. Nanotechnol. Eng. Med. 2016;6(4):041003-041003-8. doi:10.1115/1.4032012.

Rechargeable lithium-ion batteries (LIBs) are now playing crucial roles in power supply and energy storage systems. Among all types of rechargeable batteries available nowadays, LIBs are one of the most important ways to store energy because of their high energy density, high operating voltage, and low rate of self-discharge. Nonetheless, the performance of LIBs could be improved by different design parameters, such as the size of solid particles in the battery composite electrodes. Therefore, this study aims to investigate the effect of the composite electrode particles size on the electrochemical and heat generation of an LIB. A Newman's electrochemical pseudo two-dimenisonal model was used to model the LIB cell. Reversible heat produced through electrochemical reactions was calculated as well as irreversible heat originating from internal resistances in the battery cell. Our results show that smaller sizes of electrode solid particles improve the thermal characteristics of the battery, especially in higher charge and discharge currents (C-rate). Furthermore, as the solid particle sizes decrease, the battery capacity increases for various C-rates in charge and discharge cycles.

Commentary by Dr. Valentin Fuster

Research Papers: Regular Papers

J. Nanotechnol. Eng. Med. 2016;6(4):041004-041004-5. doi:10.1115/1.4033194.

Here, we report a threshold limit value (TLV) of on-chip cytotoxicity of Nepali Chiya, the Nepali traditional black tea. To demonstrate our proof-of-concept validation, we used the active sealing chip with serial dilution that can directly perform on-chip cytotoxicity testing onto the cells cultured in a petri dish. In our experiments, the TLV for mortality on HeLa cells was observed as 400 μg/ml for Nepali Chiya extract. We believe this approach would be a rapid and simple method for on-chip TLV screening of potability of tea extract at the laboratory level, and furthermore as a new potential drug supplement in pharmaceutical industries.

Commentary by Dr. Valentin Fuster
J. Nanotechnol. Eng. Med. 2016;6(4):041005-041005-9. doi:10.1115/1.4033323.

Understanding environmental factors relative to transfection protocols is key for improving genetic engineering outcomes. In the following work, the effects of temperature on a nonviral transfection procedure previously described as lance array nanoinjection are examined in context of molecular delivery of propidium iodide (PI), a cell membrane impermeable nucleic acid dye, to HeLa 229 cells. For treatment samples, variables include varying the temperature of the injection solution (3C and 23C) and the magnitude of the pulsed voltage used during lance insertion into the cells (+5 V and +7 V). Results indicate that PI is delivered at levels significantly higher for samples injected at 3C as opposed to 23C at four different postinjection intervals (t = 0, 3, 6, 9 mins; p-value ≤ 0.005), reaching a maximum value of 8.3 times the positive control for 3 C/7 V pulsed samples. Suggested in this work is that between 3 and 6 mins postinjection, a large number of induced pores from the injection event close. While residual levels of PI still continue to enter the treatment samples after 6 mins, it occurs at decreased levels, suggesting from a physiological perspective that many lance array nanoinjection (LAN) induced pores have closed, some are still present.

Commentary by Dr. Valentin Fuster

Research Papers: Fractal Engineering and Biomedicine

J. Nanotechnol. Eng. Med. 2016;6(4):041006-041006-7. doi:10.1115/1.4033126.

In this paper, we present the synthesis of nanostructures of magnetite nanoparticles (NPs) with ciprofloxacin and kanamycin antibiotics, based on self-assembling principle. The nanostructures were prepared in crystallite size, ranging 8–16 nm, in one pot addition setup and further washing steps, using only iron precursors and above-mentioned antibiotics as stabilizers. Nanostructures were analyzed by scanning electron microscopy (SEM), X-ray diffraction (XRD) analysis methods, Fourier transform infrared (FTIR) and ultraviolet (UV) spectroscopy methods. It was found that they have well-shaped spherical form and are homogeneous in size. The quantitative analysis of nanostructured antibiotics was performed by atom absorbance spectroscopy (AAS) as well as on the basis of Lambert–Beer law. Prepared nanostructures were tested on Staphylococcus aureus and Pseudomonas aeruginosa. Obtained results demonstrated that these nanostructures are able to improve antimicrobial properties and decrease the minimal inhibitory concentration (MIC) of pristine kanamycin and ciprofloxacin antibiotics.

Commentary by Dr. Valentin Fuster

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