Aligned and electrospun piezoelectric polymer fiber assembly and scaffold
Inventors
Scott-Carnell, Lisa A. • Siochi, Emilie J. • Holloway, Nancy M. • Leong, Kam W. • Kulangara, Karina
Assignees
National Aeronautics and Space Administration NASA
Publication Number
US-9005604-B2
Publication Date
2015-04-14
Expiration Date
2030-12-15
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Abstract
A scaffold assembly and related methods of manufacturing and/or using the scaffold for stem cell culture and tissue engineering applications are disclosed which at least partially mimic a native biological environment by providing biochemical, topographical, mechanical and electrical cues by using an electroactive material. The assembly includes at least one layer of substantially aligned, electrospun polymer fiber having an operative connection for individual voltage application. A method of cell tissue engineering and/or stem cell differentiation uses the assembly seeded with a sample of cells suspended in cell culture media, incubates and applies voltage to one or more layers, and thus produces cells and/or a tissue construct. In another aspect, the invention provides a method of manufacturing the assembly including the steps of providing a first pre-electroded substrate surface; electrospinning a first substantially aligned polymer fiber layer onto the first surface; providing a second pre-electroded substrate surface; electrospinning a second substantially aligned polymer fiber layer onto the second surface; and, retaining together the layered surfaces with a clamp and/or an adhesive compound.
Core Innovation
The invention provides a scaffold assembly and related methods of manufacturing and using the scaffold for stem cell culture and tissue engineering applications that at least partially mimic a native biological environment. This is achieved by providing biochemical, topographical, mechanical, and electrical cues through the use of an electroactive material. The assembly includes at least one layer of substantially aligned, electrospun polymer fiber with operative connection for individual voltage application, enabling the delivery of electrical and mechanical stimuli through bioactive fibers.
The invention addresses the problem that current scaffold designs and materials do not provide all necessary cues to mimic in vivo conditions for tissue engineering and stem cell engineering applications. Typical cell seeding environments incorporate biochemical and mechanical stimuli, but electrical cues have only recently been included. Novel scaffolds are needed that provide adequate biochemical, mechanical, topographical, and electrical stimuli in the in vitro environment to direct stem cells to differentiate along controlled pathways or develop tissue constructs.
The invention further provides methods of cell tissue engineering and stem cell differentiation using the assembly seeded with cells and applying voltage to one or more layers to produce differentiated cells or tissue constructs. The manufacturing method includes providing pre-electroded substrate surfaces, electrospinning substantially aligned polymer fiber layers onto these surfaces, and retaining the layered surfaces together with clamps or adhesives. The scaffold design also enables independent electrical stimulation of multiple layers arranged in specific configurations, enhancing the mimicry of native environments and providing precise control over stimuli application.
Claims Coverage
The patent claims three main independent inventions related to an assembly of aligned, electrospun piezoelectric polymer fibers configured for electrical stimulation, a multi-layer three-dimensional scaffolding system allowing independent electrical stimulation of layers, and assembly features for bioactive fiber stimuli delivery.
Assembly configured to utilize stimuli through bioactive fibers
An assembly comprising a first substrate film with first and second electrodes disposed thereon, and a layer of aligned, electrospun piezoelectric polymer fibers that forms outer periphery regions connected to the electrodes and an inner region suspended over the bottom surface, enabling electrical stimulation of the fiber layer.
Three dimensional scaffolding system with independent electrical stimulation
A multi-layer (at least two) assembly each having aligned electrospun piezoelectric polymer fiber layers on separate substrate films with pairs of electrodes, configured to selectively and independently apply electrical stimulation to each layer. The stimulation enables conversion of electrical signals to mechanical strain at a molecular level without macroscopic mechanical response.
Assembly with specific structural and material components for stimuli delivery
Features including the use of polyvinylidene fluoride (PVDF) as the polymer fiber material, gold electrodes affixed prior to fiber attachment on pre-electroded substrates, use of silicon adhesive to connect fibers to electrodes, substantially parallel aligned fibers, and configurations permitting individual voltage application and porous fiber layers.
The claims collectively cover scaffold assemblies composed of aligned electrospun piezoelectric polymer fibers arranged on pre-electroded substrates with electrodes allowing independent voltage application. The claims include embodiments of single and multi-layer scaffolds with structural and material details that enable applying electrical stimuli at a molecular level to influence stem cell behavior.
Stated Advantages
The scaffold provides biochemical, topographical, mechanical, and electrical cues that better mimic a native biological environment for stem cell culture and tissue engineering.
Electrical and mechanical stimuli delivered through the electroactive fibers significantly impact the proliferation and differentiation of stem cells and tissue constructs.
Aligned fiber structure controls porosity effectively, promoting cell alignment, attachment, and nutrient diffusion within a 3-D culture environment.
Use of electroactive materials like PVDF with intrinsic piezoelectric and pyroelectric properties allows simultaneous delivery of electrical and mechanical cues and offers good biocompatibility.
The scaffold design enables independent electrical stimulation of multiple fiber layers, allowing precise control over the stimulus applied to cells.
Application of low magnitude electrical fields (around 9 mV/cm) through the scaffold stimulates cellular calcium channels and enhances proliferation compared to standard culture substrates.
Documented Applications
Stem cell culture and differentiation using electrical and mechanical stimuli to direct lineage pathways and tissue construct development.
Tissue engineering applications including mimicking in vivo biological environments for improved cell proliferation and differentiation.
Potential therapeutic stem cell treatments such as for spinal cord disorders, autoimmune diseases, Parkinson's disease, myocardial infarcts, blood vessels, and skin graft tissue engineering.
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