Controlled release of glial cell line-derived neurotrophic factor from poly(ε-caprolactone) microspheres

Agbay, Andrew; Mohtaram, Nima Khadem; Willerth, Stephanie M.

doi:10.1007/s13346-013-0189-0

Cited by 17 publications

(18 citation statements)

References 49 publications

(55 reference statements)

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“…1 Microspheres were suspended in a small volume of ethanol and dispersed over SEM stubs. After the ethanol evaporated, the stubs were sputter coated with gold-palladium using an Anatech Hummer VI sputter coater.…”

Section: Microsphere Characterizationmentioning

confidence: 99%

“…Accordingly, there has been a renewed interest in poly(ɛ-caprolactone) (PCL) as a low cost alternative for fabricating scaffolds and microspheres. 1,31,51 PCL has a biodegradation rate that can extend well over a year, a desirable feature for long-term applications. 51 These properties offer a compelling case for using PCL in neural tissue engineering where the differentiation process can take up to 150 days.…”

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confidence: 99%

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Incorporation of Retinoic Acid Releasing Microspheres into Pluripotent Stem Cell Aggregates for Inducing Neuronal Differentiation

et al. 2015

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Pluripotent stem cells (PSCs) can form any specialized cell type found in the body making them an excellent tool for regenerative medicine applications. Directed differentiation of PSCs into specific phenotypes can be accomplished by introducing specific chemical cues such as the small molecule retinoic acid (RA). Expressed in the developing nervous system, RA can induce differentiation of PSCs into neural phenotypes including neurons. In this study, we encapsulated all-trans RA within poly (ɛ-caprolactone) (PCL) microspheres to generate controlled morphogen release over 28 days. RA/PCL microspheres less than ~10 µm in diameter were readily incorporated within the interstitial sites of human induced pluripotent stem cell (hiPSC) aggregates. After 5 days of culture, the microspheres did not induce cytotoxic effects and the hiPSC aggregates containing microspheres showed a decrease in the pluripotency marker SSEA-4. After 7 days of culture on laminin surfaces, aggregates expressed the neuronal marker TUJ1 and displayed extended neurite outgrowth. This approach provides consistent RA delivery throughout the aggregate and could be an effective strategy for differentiating cells in vivo.Overall, our results demonstrate that it is possible to combine hiPSC aggregates with RA/PCL microspheres for neural tissue engineering applications.

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Section: Microsphere Characterizationmentioning

confidence: 99%

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confidence: 99%

Incorporation of Retinoic Acid Releasing Microspheres into Pluripotent Stem Cell Aggregates for Inducing Neuronal Differentiation

et al. 2015

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“…We have previously encapsulated the small molecule RA inside PCL nanofibers using solution electrospinning to fabricate random and aligned encapsulated nanofibers 45 37 . To our knowledge, we are the first group to develop synthetic encapsulated PCL-BSA-GDNF nanofibers with varied topographies.…”

Section: Encapsulation Efficiency and Release Studymentioning

confidence: 99%

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

Mohtaram

Agbay

et al. 2015

J. Mater. Chem. B

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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 solutiom 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 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. factor (GDNF) promotes the survival of motor and dopaminergic neurons, making it a promising therapeutic for

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“…The collection method for these fibers can be altered to produce different types of topography. Chemical cues can be incorporated into the polymer solution to enable the resulting fibers to present bioactive factors in a controlled fashion [54][55][56]. Two variants of the electrospinning process existsolution and melt.…”

Section: Fabrication Of Fibrous Scaffolds Using Solution and Melt Elementioning

confidence: 99%

Commercializing Electrospun Scaffolds For Pluripotent Stem Cell-Based Tissue Engineering Applications

Mohtaram¹,

Karamzadeh

Shafieyan³

et al. 2017

Electrospinning

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Tissue engineering, the process of combining bioactive scaffolds often with cells to produce replacements for damaged organs, represents an enormous market opportunity. This review critically evaluates the commercialization potential of electrospun scaffolds for applications in stem cell biology, including tissue engineering. First, it provides an overview of pluripotent stem cells (PSCs) and their defining properties, pluripotency and the ability to self-renew. These cells serve as an important tool for engineering tissues, including for clinical applications. Next, we review the technique of electrospinning and its promise for fabricating cell culture substrates and scaffolds for directing tissue formation from stem cells and compare these scaffolds to existing technologies, such as hydrogels. We address the associated market for electrospun scaffolds for PSCs and its potential for growth along with highlighting the importance of 3D cell culture substrates for PSCs by analyzing the net capital invested in this market and the associated growth rate. This review finishes by detailing the current state of commercializing electrospun scaffolds along with pathways for translating these scaffolds from research laboratories into successful start-up companies and the associated challenges with this process.

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Controlled release of glial cell line-derived neurotrophic factor from poly(ε-caprolactone) microspheres

Cited by 17 publications

References 49 publications

Incorporation of Retinoic Acid Releasing Microspheres into Pluripotent Stem Cell Aggregates for Inducing Neuronal Differentiation

Incorporation of Retinoic Acid Releasing Microspheres into Pluripotent Stem Cell Aggregates for Inducing Neuronal Differentiation

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

Commercializing Electrospun Scaffolds For Pluripotent Stem Cell-Based Tissue Engineering Applications

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