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Dive into the research topics where Nima Khadem Mohtaram is active.

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Featured researches published by Nima Khadem Mohtaram.


Advanced Materials | 2017

Emerging Biofabrication Strategies for Engineering Complex Tissue Constructs

R. Daniel Pedde; Bahram Mirani; Ali Navaei; Tara Styan; Sarah Wong; Mehdi Mehrali; Ashish Thakur; Nima Khadem Mohtaram; Armin Bayati; Alireza Dolatshahi-Pirouz; Mehdi Nikkhah; Stephanie M. Willerth; Mohsen Akbari

The demand for organ transplantation and repair, coupled with a shortage of available donors, poses an urgent clinical need for the development of innovative treatment strategies for long-term repair and regeneration of injured or diseased tissues and organs. Bioengineering organs, by growing patient-derived cells in biomaterial scaffolds in the presence of pertinent physicochemical signals, provides a promising solution to meet this demand. However, recapitulating the structural and cytoarchitectural complexities of native tissues in vitro remains a significant challenge to be addressed. Through tremendous efforts over the past decade, several innovative biofabrication strategies have been developed to overcome these challenges. This review highlights recent work on emerging three-dimensional bioprinting and textile techniques, compares the advantages and shortcomings of these approaches, outlines the use of common biomaterials and advanced hybrid scaffolds, and describes several design considerations including the structural, physical, biological, and economical parameters that are crucial for the fabrication of functional, complex, engineered tissues. Finally, the applications of these biofabrication strategies in neural, skin, connective, and muscle tissue engineering are explored.


Biomedical Materials | 2013

Biomaterial-based drug delivery systems for the controlled release of neurotrophic factors

Nima Khadem Mohtaram; Amy Montgomery; Stephanie M. Willerth

This review highlights recent work on the use of biomaterial-based drug delivery systems to control the release of neurotrophic factors as a potential strategy for the treatment of neurological disorders. Examples of neurotrophic factors include the nerve growth factor, the glial cell line-derived neurotrophic factor, the brain-derived neurotrophic factor and neurotrophin-3. In particular, this review focuses on two methods of drug delivery: affinity-based and reservoir-based systems. We review the advantages and challenges associated with both types of drug delivery system and how these systems can be applied to neurological diseases and disorders. While a limited number of affinity-based delivery systems have been developed for the delivery of neurotrophic factors, we also examine the broad spectrum of reservoir-based delivery systems, including microspheres, electrospun nanofibers, hydrogels and combinations of these systems. Finally, conclusions are drawn about the current state of such drug delivery systems as applied to neural tissue engineering along with some thoughts on the future direction of the field.


Journal of Biomaterials Science-polymer Edition | 2014

Fabrication of poly (ϵ-caprolactone) microfiber scaffolds with varying topography and mechanical properties for stem cell-based tissue engineering applications

Junghyuk Ko; Nima Khadem Mohtaram; Farid Ahmed; Amy Montgomery; Michael Carlson; Patrick C. Lee; Stephanie M. Willerth; Martin B.G. Jun

Highly porous poly (ϵ-caprolactone) microfiber scaffolds can be fabricated using electrospinning for tissue engineering applications. Melt electrospinning produces such scaffolds by direct deposition of a polymer melt instead of dissolving the polymer in a solvent as performed during solution electrospinning. The objective of this study was to investigate the significant parameters associated with the melt electrospinning process that influence fiber diameter and scaffold morphology, including processing temperature, collection distance, applied, voltage and nozzle size. The mechanical properties of these microfiber scaffolds varied with microfiber diameter. Additionally, the porosity of scaffolds was determined by combining experimental data with mathematical modeling. To test the cytocompatability of these fibrous scaffolds, we seeded neural progenitors derived from murine R1 embryonic stem cell lines onto these scaffolds, where they could survive, migrate, and differentiate into neurons; demonstrating the potential of these melt electrospun scaffolds for tissue engineering applications.


Journal of Biomedical Materials Research Part A | 2015

Electrospun biomaterial scaffolds with varied topographies for neuronal differentiation of human-induced pluripotent stem cells

Nima Khadem Mohtaram; Junghyuk Ko; Craig King; Lin Sun; Nathan Muller; Martin B.G. Jun; Stephanie M. Willerth

In this study, we investigated the effect of micro and nanoscale scaffold topography on promoting neuronal differentiation of human induced pluripotent stem cells (iPSCs) and directing the resulting neuronal outgrowth in an organized manner. We used melt electrospinning to fabricate poly (ε-caprolactone) (PCL) scaffolds with loop mesh and biaxial aligned microscale topographies. Biaxial aligned microscale scaffolds were further functionalized with retinoic acid releasing PCL nanofibers using solution electrospinning. These scaffolds were then seeded with neural progenitors derived from human iPSCs. We found that smaller diameter loop mesh scaffolds (43.7 ± 3.9 µm) induced higher expression of the neural markers Nestin and Pax6 compared to thicker diameter loop mesh scaffolds (85 ± 4 µm). The loop mesh and biaxial aligned scaffolds guided the neurite outgrowth of human iPSCs along the topographical features with the maximum neurite length of these cells being longer on the biaxial aligned scaffolds. Finally, our novel bimodal scaffolds also supported the neuronal differentiation of human iPSCs as they presented both physical and chemical cues to these cells, encouraging their differentiation. These results give insight into how physical and chemical cues can be used to engineer neural tissue.


Journal of Materials Chemistry B | 2015

Development of a glial cell-derived neurotrophic factor-releasing artificial dura for neural tissue engineering applications

Nima Khadem Mohtaram; Junghyuk Ko; Andrew Agbay; D. Rattray; P. O. Neill; A. Rajwani; R. Vasandani; H. L. Thu; Martin B.G. Jun; Stephanie M. Willerth

Encapsulated electrospun nanofibers can serve as an artificial dura mater, the membrane that surrounds the brain and spinal cord, due to their desirable drug delivery properties. Such nanofiber scaffolds can be used to deliver drugs such as glial cell-derived neurotrophic factor (GDNF). GDNF promotes the survival of both dopaminergic and motor neurons, making it an important target for treatment of central nervous system injuries and disorders. This work focuses on designing a novel class of encapsulated poly(ε-caprolactone) (PCL) nanofiber scaffolds with different topographies (random and aligned) that generate controlled release of GDNF to potentially serve as a suitable substitute for the dura mater during neurosurgical procedures. Random and aligned scaffolds fabricated using solution electrospinning were characterized for their physical properties and their ability to release GDNF over one month. GDNF bioactivity was confirmed using a PC12 cell assay with the highest concentrations of released GDNF (∼341 ng mL-1 GDNF) inducing the highest levels of neurite extension (∼556 μm). To test the cytocompatibility of aligned GDNF encapsulated PCL nanofibers, we successfully seeded neural progenitors derived from human induced pluripotent stem cells (hiPSCs) onto the scaffolds where they survived and differentiated into neurons. Overall, this research demonstrates the potential of such substrates to act as artificial dura while delivering bioactive GDNF in a controlled fashion. These scaffolds also support the culture and differentiation of hiPSC-derived neural progenitors, suggesting their biocompatibility with the cells of the central nervous system.


Journal of Micromechanics and Microengineering | 2014

Using mathematical modeling to control topographical properties of poly (ε-caprolactone) melt electrospun scaffolds

Junghyuk Ko; S.K. Bhullar; Nima Khadem Mohtaram; Stephanie M. Willerth; Martin B.G. Jun

Melt electrospinning creates fibrous scaffolds using direct deposition. The main challenge of melt electrospinning is controlling the topography of the scaffolds for tissue engineering applications. Mathematical modeling enables a better understanding of the parameters that determine the topography of scaffolds. The objective of this study is to build two types of mathematical models. First, we modeled the melt electrospinning process by incorporating parameters such as nozzle size, counter electrode distance and applied voltage that influence fiber diameter and scaffold porosity. Our second model describes the accumulation of the extruded microfibers on flat and round surfaces using data from the microfiber modeling. These models were validated through the use of experimentally obtained data. Scanning electron microscopy (SEM) was used to image the scaffolds and the fiber diameters were measured using Quartz-PCI Image Management Systems® in SEM to measure scaffold porosity.


Cells Tissues Organs | 2016

Biomaterial Strategies for Delivering Stem Cells as a Treatment for Spinal Cord Injury

Andrew Agbay; John M. Edgar; Meghan Robinson; Tara Styan; Krista Wilson; Julian Schroll; Junghyuk Ko; Nima Khadem Mohtaram; Martin B.G. Jun; Stephanie M. Willerth

Ongoing clinical trials are evaluating the use of stem cells as a way to treat traumatic spinal cord injury (SCI). However, the inhibitory environment present in the injured spinal cord makes it challenging to achieve the survival of these cells along with desired differentiation into the appropriate phenotypes necessary to regain function. Transplanting stem cells along with an instructive biomaterial scaffold can increase cell survival and improve differentiation efficiency. This study reviews the literature discussing different types of instructive biomaterial scaffolds developed for transplanting stem cells into the injured spinal cord. We have chosen to focus specifically on biomaterial scaffolds that direct the differentiation of neural stem cells and pluripotent stem cells since they offer the most promise for producing the cell phenotypes that could restore function after SCI. In terms of biomaterial scaffolds, this article reviews the literature associated with using hydrogels made from natural biomaterials and electrospun scaffolds for differentiating stem cells into neural phenotypes. It then presents new data showing how these different types of scaffolds can be combined for neural tissue engineering applications and provides directions for future studies.


Micromachines | 2016

Microfluidic-Based Multi-Organ Platforms for Drug Discovery

Ahmad Rezaei Kolahchi; Nima Khadem Mohtaram; Hassan Pezeshgi Modarres; Mohammad Hossein Mohammadi; Armin Geraili; Parya Jafari; Mohsen Akbari; Amir Sanati-Nezhad

Development of predictive multi-organ models before implementing costly clinical trials is central for screening the toxicity, efficacy, and side effects of new therapeutic agents. Despite significant efforts that have been recently made to develop biomimetic in vitro tissue models, the clinical application of such platforms is still far from reality. Recent advances in physiologically-based pharmacokinetic and pharmacodynamic (PBPK-PD) modeling, micro- and nanotechnology, and in silico modeling have enabled single- and multi-organ platforms for investigation of new chemical agents and tissue-tissue interactions. This review provides an overview of the principles of designing microfluidic-based organ-on-chip models for drug testing and highlights current state-of-the-art in developing predictive multi-organ models for studying the cross-talk of interconnected organs. We further discuss the challenges associated with establishing a predictive body-on-chip (BOC) model such as the scaling, cell types, the common medium, and principles of the study design for characterizing the interaction of drugs with multiple targets.


Journal of Micromechanics and Microengineering | 2015

Mathematical model for predicting topographical properties of poly (ε-caprolactone) melt electrospun scaffolds including the effects of temperature and linear transitional speed

Junghyuk Ko; Nima Khadem Mohtaram; Patrick C. Lee; Stephanie M. Willerth; Martin B.G. Jun

Funding support from Natural Sciences and Engineering Research Council (NSERC) Discovery Grants is acknowledged. The authors would also like to acknowledge the Advanced Microscopy Facility at the University of Victoria.


Journal of Biological Engineering | 2017

Modeling the behavior of human induced pluripotent stem cells seeded on melt electrospun scaffolds

Meghan E. Hall; Nima Khadem Mohtaram; Stephanie M. Willerth; Roderick Edwards

BackgroundHuman induced pluripotent stem cells (hiPSCs) can form any tissue found in the body, making them attractive for regenerative medicine applications. Seeding hiPSC aggregates into biomaterial scaffolds can control their differentiation into specific tissue types. Here we develop and analyze a mathematical model of hiPSC aggregate behavior when seeded on melt electrospun scaffolds with defined topography.ResultsWe used ordinary differential equations to model the different cellular populations (stem, progenitor, differentiated) present in our scaffolds based on experimental results and published literature. Our model successfully captures qualitative features of the cellular dynamics observed experimentally. We determined the optimal parameter sets to maximize specific cellular populations experimentally, showing that a physiologic oxygen level (∼ 5%) increases the number of neural progenitors and differentiated neurons compared to atmospheric oxygen levels (∼ 21%) and a scaffold porosity of ∼ 63% maximizes aggregate size.ConclusionsOur mathematical model determined the key factors controlling hiPSC behavior on melt electrospun scaffolds, enabling optimization of experimental parameters.

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Junghyuk Ko

University of Victoria

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Lin Sun

University of Victoria

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