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Date: 08 January 2009
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An Interdisciplinary Researchers Team has Studied Ground-Breaking Work on a New Type of Polymer that Shows CMA  

Topic Name: An Interdisciplinary Researchers Team has Studied Ground-Breaking Work on a New Type of Polymer that Shows CMA

Category: Polymer Interfaces and Macromolecular Assemblies

Research persons: Case Researchers

Location: Case Western Reserve University, United States

Details

An Interdisciplinary Researchers Team has Studied Ground-Breaking Work on a New Type of Polymer that Shows CMA

An interdisciplinary team of researchers from the departments of macromolecular science and engineering and biomedical engineering at the Case School of Engineering and the Louis Stokes Cleveland Department of Veterans Affairs Medical Center has published ground-breaking work on a new type of polymer that displays chemoresponsive mechanic adaptability -- meaning the polymer can change from hard to soft plastic and vice versa in seconds when exposed to liquid -- in the March 7, 2008, issue of Science, one of the world's most prestigious scholarly journals covering all aspects of science.

Jeffrey R. Capadona, associate investigator at the VA's Advanced Platform Technology (APT) Center, graduate student Kadhiravan Shanmuganathan, and Case Western Reserve University professors and APT investigators Dustin Tyler (biomedical engineering), Stuart Rowan (macromolecular science) and Christoph Weder (macromolecular science) have unveiled a radically new approach for developing polymer nanocomposites which alter their mechanical properties when exposed to certain chemical stimuli.

"We can engineer these new polymers to change their mechanical properties -- in particular stiffness and strength -- in a programmed fashion when exposed to a specific chemical," says Weder, one of the senior authors of the paper.

"The materials on which we reported in Science were designed to change from a hard plastic -- think of a CD case -- to a soft rubber when brought in contact with water," adds Rowan, who has been Weder's partner on the project for almost six years.

"Our new materials were tailored to respond specifically to water and to exhibit minimal swelling, so they don't soak up water like a sponge," saud Shanmuganathan.

In their new approach, the team used a biomimetic approach -- or mimicking biology -- copying nature's design found in the skin of sea cucumbers.

"These creatures can reversibly and quickly change the stiffness of their skin. Normally it is very soft, but, for example, in response to a threat, the animal can activate its 'body armor' by hardening its skin," explains Capadona, who has a sea cucumber in his aquarium. Marine biologists have shown in earlier studies that the switching effect in the biological tissue is derived from a distinct nanocomposite structure in which highly rigid collagen nanofibers are embedded in a soft connective tissue. The stiffness is mediated by specific chemicals that are secreted by the animal's nervous system and which control the interactions among the collagen nanofibers. When connected, the nanofibers form a reinforcing network which increases the overall stiffness of the material considerably, when compared to the disconnected (soft) state.

Building on their recent success on the fabrication of artificial polymer nanocomposites containing rigid cellulose nanofibers, which earned them the December 2007 cover of Nature Nanotechnology, the team mimicked the architecture nature 'designed' for the sea cucumbers and created artificial materials that display similar mechanical morphing characteristics.

The Case Western Reserve/VA team is specifically interested in using such dynamic mechanical materials in biomedical applications, for example as adaptive substrates for intracortical microelectrodes. These devices are being developed as part of 'artificial nervous systems' that have the potential to help treat patients that suffer from medical conditions such as Parkinson's disease, stroke or spinal cord injuries, i.e., disorders in which the body's interface to the brain is compromised. A problem observed in experimental studies is that the quality of the brain signals recorded by such microelectrodes usually degrades within a few months after implantation, making chronic applications challenging. One hypothesis for this failure is that the high stiffness of these electrodes, which is required for their insertion, causes damage to the surrounding, very soft brain tissue over time. "We believe that electrodes that use mechanically adaptive polymer as substrate could alleviate this problem" explains Dustin Tyler, who specializes in neural interfacing and functional electrical stimulation. The development and testing of experimental microelectrodes that involve the new adaptive materials is currently underway. "That's why we designed our first materials to respond to water" explains Weder. "This allows the rigid electrodes to become soft when implanted into the water-rich brain" he adds.

Note for Nanocomposite
Nanocomposites are materials that are created by introducing nanoparticulates (often referred to as filler) into a macroscopic sample material (often referred to as the matrix). This is part of the growing field of nanotechnology. After adding nanoparticulates to the matrix material, the resulting nanocomposite may exhibit drastically enhanced properties. For example, adding carbon nanotubes tends to drastically add to the electrical and thermal conductivity. Other kinds of nanoparticulates may result in enhanced optical properties, dielectric properties or mechanical properties such as stiffness and strength. In general, the nanosubstance is dispersed into the matrix during processing. The percentage by weight (called mass fraction) of the nanoparticulates introduced is able to remain very low (on the order of 0.5% to 5%) due to the incredibly high surface area to volume ratio of nanoparticulates. Much research is going into developing more efficient combinations of matrix and filler materials and into better controlling the production process.

Note for Biomimetic Material
Biomimetic materials are materials that have been designed such that they elicit specified cellular responses mediated by interactions with scaffold-tethered peptides from extracellular matrix (ECM) proteins; essentially, the incorporation of cell-binding peptides into biomaterials via chemical or physical modification.
Such peptides include both native long chains of ECM proteins as well as short peptide sequences derived from intact ECM proteins. The idea is that the biomimetic material will mimic some of the roles that an extracellular matrix plays in neural tissue. In addition to promoting cellular growth and mobilization, the incorporated peptides could also mediate material degradation by specific protease enzymes or initiate cellular responses not present in a local native tissue. In the beginning, long chains of ECM proteins including fibronectin (FN), vitronectin (VN), and laminin (LN) were used, but more recently the advantages of using short peptides have been discovered. Short peptides are more advantageous because, unlike the long chains that fold randomly upon adsorption causing the active protein domains to be sterically unavailable, short peptides remain stable and do not hide the receptor binding domains when adsorbed. Another advantage to short peptides is that they can be replicated more economically due to the smaller size. A bi-functional cross-linker with a long spacer arm is used to tether peptides to the substrate surface. If a functional group is not available for attaching the cross-linker, photochemical immobilization may be used. In addition to modifying the surface, biomaterials can be modified in bulk, meaning that the cell signaling peptides and recognition sites are present not just on the surface but also throughout the bulk of the material. The strength of cell attachment, cell migration rate, and extent of cytoskeletal organization formation is determined by the receptor biding to the ligand bound to the material; thus, receptor-ligand affinity, the density of the ligand, and the spatial distribution of the ligand must be carefully considered when designing a biomimetic material.
Many studies utilize laminin-1 when designing a biomimetic material. Laminin is a component of the extracellular matrix that is able to promote neuron attachment and differentiation, in addition to axon growth guidance. Its primary functional site for bioactivity is its core protein domain isoleucine-lysine-valine-alanine-valine (IKVAV), which is located in the α-1 chain of laminin. A recent study by Wu, Zheng et al., synthesized a self-assembled IKVAV peptide nanofiber and tested its effect on the adhesion of neuron-like pc12 cells. Early cell adhesion is very important for preventing cell degeneration; the longer cells are suspended in culture, the more likely they are to degenerate. The purpose was to develop a biomaterial with good cell adherence and bioactivity with IKVAV, which is able to inhibit differentiation and adhesion of glial cells in addition to promoting neuronal cell adhesion and differentiation. The IKVAV peptide domain is on the surface of the nanofibers so that it is exposed and accessible for promoting cell contact interactions. The IKVAV nanofibers promoted stronger cell adherence than the electrostatic attraction induced by poly-L-lysine, and cell adherence increased with increasing density of IKVAV until the saturation point was reached. IKVAV does not exhibit time dependent effects because the adherence was shown to be the same at 1 hour and at 3 hours.

Note for Nanofiber
Nanofibers are defined as fibers with diameters less than 100 nanometers. They can be produced by interfacial polymerization and electrospinning. Carbon nanofibers are graphitized fibers produced by catalytic synthesis.

Applications
In one study, combined neural stem cells with carbon nanofibers triggered neural tissue regeneration in the brains of rats that had suffered a simulated stroke. On their own, neither nanofibers nor stem cells could heal the rats.
Napkins with nanofibers contain antibodies against numerous biohazards and chemicals that signal by changing color (potentially useful in identifying bacteria in kitchens).
In wound healing nanofibers assemble at the injury site and stay put, drawing the body's own growth factors to the injury site.
Donaldson develops nanofiber filter media for new air and liquid filtration applications, such as vacuum cleaners.
Other applications include industrial and high-tech applications for aerospace, capacitors, transistors, battery separators, energy storage, fuel cells and information technology.

Note for Parkinson's Disease
Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the central nervous system that often impairs the sufferer's motor skills and speech.
Parkinson's disease belongs to a group of conditions called movement disorders. It is characterized by muscle rigidity, tremor, a slowing of physical movement (bradykinesia) and, in extreme cases, a loss of physical movement (akinesia). The primary symptoms are the results of decreased stimulation of the motor cortex by the basal ganglia, normally caused by the insufficient formation and action of dopamine, which is produced in the dopaminergic neurons of the brain. Secondary symptoms may include high level cognitive dysfunction and subtle language problems. PD is both chronic and progressive.
PD is the most common cause of chronic progressive parkinsonism, a term which refers to the syndrome of tremor, rigidity, bradykinesia and postural instability. PD is also called "primary parkinsonism" or "idiopathic PD" (classically meaning having no known cause although this term is not strictly true in light of the plethora of newly discovered genetic mutations). While many forms of parkinsonism are "idiopathic", "secondary" cases may result from toxicity most notably drugs, head trauma, or other medical disorders.
Parkinson disease affects movement (motor symptoms). Typical other symptoms include disorders of mood, behavior, thinking, and sensation (non-motor symptoms). Individual patients' symptoms may be quite dissimilar and progression of the disease is also distinctly individual.
There are currently no blood or laboratory tests that have been proven to help in diagnosing PD. Therefore the diagnosis is based on medical history and a neurological examination. The disease can be difficult to diagnose accurately. The Unified Parkinson's Disease Rating Scale is the primary clinical tool used to assist in diagnosis and determine severity of PD. Indeed, only 75% of clinical diagnoses of PD are confirmed at autopsy. Early signs and symptoms of PD may sometimes be dismissed as the effects of normal aging. The physician may need to observe the person for some time until it is apparent that the symptoms are consistently present. Usually doctors look for shuffling of feet and lack of swing in the arms. Doctors may sometimes request brain scans or laboratory tests in order to rule out other diseases. However, CT and MRI brain scans of people with PD usually appear normal.
Clinical practice guidelines introduced in the UK in 2006 state that the diagnosis and follow-up of Parkinson's disease should be done by a specialist in the disease, usually a neurologist with an interest in movement disorders.

In figure, Sea cucumbers inspired the design of chemo-responsive nanocomposite with adaptive mechanical properties


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