Nanoengineering the Heart: Conductive Scaffolds Enhance Connexin 43 Expression

You, Jin-Oh; Rafat, Marjan; Ye, George J.C.; Auguste, Debra T.

doi:10.1021/nl201514a

Cited by 283 publications

(230 citation statements)

References 65 publications

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“…This is an active research field and numerous beautiful examples have been described in the literature that has inspired this work. [191][192][193] …”

Section: Chapter 4 Multifunctional Biomaterialsmentioning

confidence: 99%

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Multifunctional Biomimetic Scaffolds Tailored for Cardiac Regeneration

Wickham¹

2015

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Linköping 2015Cover: Scanning Electron Microscopy image of a mesenchymal cell on polycaprolactone fibers.During the course of the research presented in this thesis, Abeni Wickham, was enrolled in Forum Scientium, a multidisciplinary graduate school at Linköping University. ColophonThis thesis is not only the summation of 5 years of research, but also a material manifestation of my happiness.It has not been straightforward and I have had numerous failures, disappointments and doubts. These have always been positive moments, as each difficult moment gave me the chance to choose a different path to still achieve my research goals.I have spent the past few years fighting for what I love the most; answering the questions that I ask myself every day. I have been lucky to have two supervisors, Daniel and Bo who pushed me to be better scientifically and family/friends who kept me grounded.During this work, I found who I really am; this thesis is a representation of me.ii Abstract Nature has had millions of years to perfect the structural components of the human body, but has also produced the dysfunctions that result in the cancers and diseases, which ruin that perfection. Congenital heart defects, and myocardial infarction lead to scarring that remodels heart muscle, decreasing the contractility of the heart, with profound consequences for the host. Regenerative medicine is the study of strategies to return diseased body parts to their evolutionarily optimum structure.Cells alone cannot develop into functional tissue, as they require mechanical support and chemical signals from the extracellular matrix in order to play the correct role in the body. In order to imitate the process of tissue formation optimized by nature, scaffolds are developed as the architectural support for tissue regeneration. To mimic the elasticity and strength seen in the heart muscle is one of the major scientific conundrums of our time. The development of new multifunctional materials for scaffolds is an accepted solution for repairing failing heart muscle. In this thesis I accept the notion that endogenous cardiac cells can play a major role in addressing this problem, if we can attract them to the site of defect or injury and make them proliferate. I then proceed to show how improving on a commonly used synthetic polymer was used to develop two new biomaterials.Polycaprolactone (PCL) fibers and sheets were studied for their ability to adsorb proteins based on their surface energies. We found that although the wettability of the PCL might be similar to positive controls for cell attachment, the large differences in surface energies may account for the increased serum protein adsorption and limit cell adhesion. The effect of fiber morphology was then investigated with respect to proliferation of mesenchymal stem cells and cardiac progenitor cells. PCL was also mechanically enhanced with thiophene conjugated single walled carbon nanotubes (T-CNT); where small concentrations of the T-CNT allowed for a 2.5 fold increase in the percentage of elong...

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“…This is an active research field and numerous beautiful examples have been described in the literature that has inspired this work. [191][192][193] …”

Section: Chapter 4 Multifunctional Biomaterialsmentioning

confidence: 99%

“…206 Interestingly, an increase in cardiac cell electrical coupling through the gap junction proteins can be seen on the materials without external electrical stimulation. [191][192][193] …”

Section: Conductive Biomaterialsmentioning

confidence: 99%

Multifunctional Biomimetic Scaffolds Tailored for Cardiac Regeneration

Wickham¹

2015

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“…19 The properties of this extracellular matrix-like architecture can be adjusted by incorporation of nanomaterials such as carbon nanotubes, nanowires, and nanoparticles. 20 For instance, You et al 21 developed an electrically conductive hybrid hydrogel scaffold based on gold nanoparticles homogeneously synthesized throughout a polymer template gel. The expression of connexin-43 increased in neonatal cardiomyocytes grown on the scaffold, suggesting that an electrically active scaffold impregnated with gold can enhance cardiomyocyte function.…”

Section: Applications Of Nanoengineered Scaffolds In Tissue Growth Anmentioning

confidence: 99%

“…The expression of connexin-43 increased in neonatal cardiomyocytes grown on the scaffold, suggesting that an electrically active scaffold impregnated with gold can enhance cardiomyocyte function. 21 Nanoscale topographical features (100 nm to 1 µm in size) defined on cell culture substrates can direct cell behavior, including polarity, migration, proliferation, and differentiation. For example, nanotopographical variations in the cell adhesion substrate can regulate differentiation of human mesenchymal stem cells towards adipocytes or osteocytes.…”

Section: Applications Of Nanoengineered Scaffolds In Tissue Growth Anmentioning

confidence: 99%

Emerging nanotechnology approaches in tissue engineering and regenerative medicine

Kim¹,

Ahn²,

Dvir³

et al. 2014

IJN

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“…Auguste et al showed that spherical gold nanoparticles (AuNPs) could be synthesized in a HEMA-based scaffold, leading to an increase in conductivity of the materials. 12 Silicone field effective transistors embedded in Matrigel and synthetic scaffolds has also been shown to be conductive enough to enable real time monitoring of electrochemical signals from cardiomyocytes and neural cells. 13 Most of these systems, however ingenious, require complicated fabrication procedures and use of materials that are not yet approved for medical implants.…”

Section: Introductionmentioning

confidence: 99%

Electroactive biomimetic collagen-silver nanowire composite scaffolds

Wickham

Vagin²,

Khalaf

et al. 2016

Nanoscale

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Electroactive biomaterials are used in a number of applications, including scaffolds for neural and cardiac regeneration. Most electrodes and conductive scaffolds for tissue regeneration are based on synthetic materials that have limited biocompatibility and often display a large mismatch in mechanical properties with the surrounding tissue. In this work we have developed a nanocomposite material prepared from self-assembled collagen and silver nanowires (AgNW) that display electrical properties analogous to electrodes used in the clinic. The AgNW concentration of the nanocomposites was optimized to stimulate proliferation of isolated embryonic cardiomyocytes. In addition, the AgNWs renders the nanocomposites antimicrobial against both Gram-negative Escherichia coli and Gram-positive Staphylococcus epidermidis.The mechanical properties of the nanocomposites were further characterized in physiological conditions and showed a dynamic modulus within the lower kPa range, suitable for embryonic cardiomyocyte proliferation. An in depth electrochemical analysis of the materials in the wet state showed a charge storage capacity of 12.28 mC cm -2 , and charge injection capacity of 0.33 mC cm -2 , comparable to electrode materials, such as iridium oxide and polypyrrole, currently used for electrical stimulation of tissues. The collagen/AgNW composites are thus multifunctional structural scaffolds that promote embryonic cardiomyocyte function, with the ability to store and inject charges, along with providing antimicrobial resistance.3

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Nanoengineering the Heart: Conductive Scaffolds Enhance Connexin 43 Expression

Cited by 283 publications

References 65 publications

Multifunctional Biomimetic Scaffolds Tailored for Cardiac Regeneration

Multifunctional Biomimetic Scaffolds Tailored for Cardiac Regeneration

Emerging nanotechnology approaches in tissue engineering and regenerative medicine

Electroactive biomimetic collagen-silver nanowire composite scaffolds

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