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Cardiovascular diseases, including myocardial infarction, are the cause of significant morbidity and mortality globally. Tissue engineering is a key emerging treatment method for supporting and repairing the cardiac scar tissue caused by myocardial infarction. Creating cell supportive scaffolds that can be directly implanted on a myocardial infarct is an attractive solution. Hydrogels made of collagen are highly biocompatible materials that can be molded into a range of shapes suitable for cardiac patch applications. The addition of mechanically reinforcing materials, carbon nanotubes, at subtoxic levels allows for the collagen hydrogels to be strengthened, up to a toughness of 30 J m-1 and a two to threefold improvement in Youngs' modulus, thus improving their viability as cardiac patch materials. The addition of carbon nanotubes is shown to be both nontoxic to stem cells, and when using single-walled carbon nanotubes, supportive of live, beating cardiac cells, providing a pathway for the further development of a cardiac patch., Funding agencies: Linkoping Initiative in Life Science Technologies (LIST); Central ALF Matching Grant from Landstinget i Ostergotland [LIO-344071]; European Research Agency [304209]; GeCONiI [POIG.02.03.01-24-099/13]

The combination of stem cell therapy with a supportive scaffold is a promising approach to improving cardiac tissue engineering. Stem cell therapy can be used to repair nonfunctioning heart tissue and achieve myocardial regeneration, and scaffold materials can be utilized in order to successfully deliver and support stem cells in vivo. Current research describes passive scaffold materials; here an electroactive scaffold that provides electrical, mechanical, and topographical cues to induced human pluripotent stem cells (iPS) is presented. The poly(lactic-co-glycolic acid) fiber scaffold coated with conductive polymer polypyrrole (PPy) is capable of delivering direct electrical and mechanical stimulation to the iPS. The electroactive scaffolds demonstrate no cytotoxic effects on the iPS as well as an increased expression of cardiac markers for both stimulated and unstimulated protocols. This study demonstrates the first application of PPy as a supportive electroactive material for iPS and the first development of a fiber scaffold capable of dynamic mechanical actuation., Funding Agencies|Linkoping University, Integrative Regenerative Medicine (IGEN) Center; Swedish Research Council [VR-2014-3079]; COST-Action [MP1003]; Knut och Alice Wallenberg Commemorative Fund; GeCONiI [POIG.02.03.01-24-099/13]; European Research Agency

Polypyrrole (PPy) is a conducting polymer that enables controlled drug release upon electrical stimulation. We characterized the biocompatibility of PPy with human primary osteoblasts, and the effect of dopants. We investigated the biocompatibility of PPy comprising various dopants, i.e. p-toluene sulfonate (PPy-pTS), chondroitin sulfate (PPy-CS), or dodecylbenzenesulfonate (PPy-DBS), with human primary osteoblasts. PPy-DBS showed the roughest appearance of all surfaces tested, and its wettability was similar to the gold-coated control. The average number of attached cells was 45% higher on PPy-DBS than on PPyCS or PPy-pTS, although gene expression of the proliferation marker Ki-67 was similar in osteoblasts on all surfaces tested. Osteoblasts seeded on PPy-DBS or gold showed similar vinculin attachment points, vinculin area per cell area, actin filament structure, and Ferets diameter, while cells seeded on PPY-CS or PPY-pTS showed disturbed focal adhesions and were enlarged with disorganized actin filaments. Osteoblasts grown on PPy-DBS or gold showed enhanced alkaline phosphatase activity and osteocalcin gene expression, but reduced osteopontin gene expression compared to cells grown on PPy-pTS and PPy-CS. In conclusion, PPy doped with DBS showed excellent biocompatibility, which resulted in maintaining focal adhesions, cell morphology, cell number, alkaline phosphatase activity, and osteocalcin gene expression. Taken together, conducting polymers doped with DBS are well tolerated by osteoblasts. Our results could provide a basis for the development of novel orthopedic or dental implants with controlled release of antibiotics and pharmaceutics that fight infections or focally enhance bone formation in a tightly controlled manner., Funding Agencies|VINNOVA [2012-04409]; Vetenskapradet [521-2013-2593]; Linkoping Initiative in Life Science Technologies (LIST)

Cardiac tissue engineering via the use of stem cells is the future for repairing impaired heart function that results from a myocardial infarction. Developing an optimised platform to support the stem cells is vital to realising this, and through utilising new smart materials such as conductive polymers we can provide a multi-pronged approach to supporting and stimulating the stem cells via engineered surface properties, electrical, and electromechanical stimulation. Here we present a fundamental study on the viability of cardiac progenitor cells on conductive polymer surfaces, focusing on the impact of surface properties such as roughness, surface energy, and surface chemistry with variation of the polymer dopant molecules. The conductive polymer materials were shown to provide a viable support for both endothelial and cardiac progenitor cells, while the surface energy and roughness were observed to influence viability for both progenitor cell types. Characterising the interaction between the cardiac progenitor cells and the conductive polymer surface is a critical step towards optimising these materials for cardiac tissue regeneration, and this study will advance the limited knowledge on biomaterial surface interactions with cardiac cells.