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Polycaprolactone–thiophene-conjugated carbon nanotube meshes as scaffolds for cardiac progenitor cells
Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, The Institute of Technology. (Integrative Regenerative Medicine (IGEN) Centre)
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Karolinska Institutet, Stockholm, Sweden. (Integrative Regenerative Medicine (IGEN) Centre)
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology. (Integrative Regenerative Medicine (IGEN) Centre)
Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, The Institute of Technology. (Integrative Regenerative Medicine (IGEN) Centre)
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2014 (English)In: Journal of Biomedical Materials Research. Part B - Applied biomaterials, ISSN 1552-4973, E-ISSN 1552-4981, Vol. 102, no 7, 1553-1561 p.Article in journal (Refereed) Published
Abstract [en]

The myocardium is unable to regenerate itself after infarct, resulting in scarring and thinning of the heart wall. Our objective was to develop a patch to buttress and bypass the scarred area, while allowing regeneration by incorporated cardiac stem/progenitor cells (CPCs). Polycaprolactone (PCL) was fabricated as both sheets by solvent casting, and fibrous meshes by electrospinning, as potential patches, to determine the role of topology in proliferation and phenotypic changes to the CPCs. Thiophene-conjugated carbon nanotubes (T-CNTs) were incorporated to enhance the mechanical strength. We showed that freshly isolated CPCs from murine hearts neither attached nor spread on the PCL sheets, both with and without T-CNT. As electrospun meshes, however, both PCL and PCL/T-CNT supported CPC adhesion, proliferation, and differentiation. The incorporation of T-CNT into PCL resulted in a significant increase in mechanical strength but no morphological changes to the meshes. In turn, proliferation, but not differentiation, of CPCs into cardiomyocytes was enhanced in T-CNT containing meshes. We have shown that changing the topology of PCL, a known hydrophobic material, dramatically altered its properties, in this case, allowing CPCs to survive and differentiate. With further development, PCL/T-CNT meshes or similar patches may become a viable strategy to aid restoration of the postmyocardial infarction myocardium.

Place, publisher, year, edition, pages
John Wiley & Sons, 2014. Vol. 102, no 7, 1553-1561 p.
Keyword [en]
topology, carbon nanotubes, polycaprolactone, cardiac progenitor cells, electrospun meshes
National Category
Clinical Medicine Basic Medicine Physical Sciences
Identifiers
URN: urn:nbn:se:liu:diva-111488DOI: 10.1002/jbm.b.33136ISI: 000342963000020PubMedID: 24664884OAI: oai:DiVA.org:liu-111488DiVA: diva2:756733
Available from: 2014-10-19 Created: 2014-10-19 Last updated: 2017-12-05Bibliographically approved
In thesis
1. Multifunctional Biomimetic Scaffolds Tailored for Cardiac Regeneration
Open this publication in new window or tab >>Multifunctional Biomimetic Scaffolds Tailored for Cardiac Regeneration
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

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 elongation, while retaining the proliferation profile of the cardiac progenitor cells. Although PCL is a well-known implant material, the ability to attract and adhere cardiac cells was limited. Therefore we sought to develop new biomaterials with fiber morphologies similar to the muscle fiber of the heart, but with surface energies similar to positive controls for cell attachment. Poly[2,3-bis-(3-octyloxyphenyl)quinoxaline-5,8-diyl-alt-thiophene-2,5-diyl] (TQ1) was then explored as a ribbon fiber and compared to collagen with embryonic cardiac cells, in vitro, and then implanted into rats for in vivo long term evaluations. The cardiac cells had a preferential adhesion to the TQ1 fibers, and in vivo, the fibers attracted more blood vessels and regrew functional tissue compared to the collagen controls. TQ1 fibers had the added ability to emit light in the near infrared region, which would allow for consistent tracking of the material. Although this material offered the morphological preference for the cardiac cells, it does not degrade and nor did it offer electrical conductivity. The heart muscle is an electrically active muscle. The dead tissue that is formed in the ischemic area loses its ability to  transfer the electrical signals. Hence, I have then developed collagen fibrous materials with silver nanowires to help store and inject charges that would be generated during the contraction of the heart muscle. The silver nanowires served to help carry charges whilst providing resistance to bacterial growth on the material. The collagen/silver nanowires composites were mechanically apt for the culture of embryonic cardiac cells.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2015. 80 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1686
National Category
Physical Sciences Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-120773 (URN)10.3384/diss.diva-120773 (DOI)978-91-7519-021-1 (ISBN)
Public defence
2015-08-28, Planck, Fysikhuset, Campus Valla, Linköping, 09:15 (English)
Opponent
Supervisors
Available from: 2015-08-24 Created: 2015-08-24 Last updated: 2017-01-11Bibliographically approved

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