We report a simple method to fabricate macroscopic, 3-D, free standing, all-carbon scaffolds (porous structures) using multiwalled carbon nanotubes (MWCNTs) as the starting materials. The scaffolds prepared by radical initiated thermal crosslinking, and annealing of MWCNTs possess macroscale interconnected pores, robust structural integrity, stability, and conductivity. The porosity of the three-dimensional structure can be controlled by varying the amount of radical initiator, thereby allowing the design of porous scaffolds tailored towards specific potential applications. This method also allows the fabrication of 3-D scaffolds using other carbon nanomaterials such as single-walled carbon nanotubes, fullerenes, and graphene indicating that it could be used as a versatile method for 3-D assembly of carbon nanostructures with pi bond networks.

We have developed an engineered heart tissue (EHT) system that uses laser-cut sheets of decellularized myocardium as scaffolds. This material enables formation of thin muscle strips whose biomechanical characteristics are easily measured and manipulated. To create EHTs, sections of porcine myocardium were laser-cut into ribbon-like shapes, decellularized, and mounted in specialized clips for seeding and culture. Scaffolds were first tested by seeding with neonatal rat ventricular myocytes. EHTs beat synchronously by day five and exhibited robust length-dependent activation by day 21. Fiber orientation within the scaffold affected peak twitch stress, demonstrating its ability to guide cells toward physiologic contractile anisotropy. Scaffold anisotropy also made it possible to probe cellular responses to stretch as a function of fiber angle. Stretch that was aligned with the fiber direction increased expression of brain natriuretic peptide, but off-axis stretches (causing fiber shear) did not. The method also produced robust EHTs from cardiomyocytes derived from human embryonic stem cells and induced pluripotent stem cells (hiPSC). hiPSC-EHTs achieved maximum peak stress of 6.5 mN/mm2 and twitch kinetics approaching reported values from adult human trabeculae. We conclude that laser-cut EHTs are a viable platform for novel mechanotransduction experiments and characterizing the biomechanical function of patient-derived cardiomyoctyes.

Cardiac disorders are the main cause of mortality in autosomaldominant polycystic kidney disease (ADPKD). However, how mutated polycystins predispose patients with ADPKD to cardiac pathologies before development of renal dysfunction is unknown. We investigate the effect of decreased levels of polycystin 2 (PC2), a calcium channel that interacts with the ryanodine receptor, on myocardial function. We hypothesize that heterozygous PC2 mice (Pkd2 +/− ) undergo cardiac remodeling as a result of changes in calcium handling, separate from renal complications. We found that Pkd2 +/− cardiomyocytes have altered calcium handling, independent of desensitized calcium-contraction coupling. Paradoxically, in Pkd2 +/− mice, protein kinase A (PKA) phosphorylation of phospholamban (PLB) was decreased, whereas PKA phosphorylation of troponin I was increased, explaining the decoupling between calcium signaling and contractility. In silico modeling supported this relationship. Echocardiography measurements showed that Pkd2 +/− mice have increased left ventricular ejection fraction after stimulation with isoproterenol (ISO), a β-adrenergic receptor (βAR) agonist. Blockers of βAR-1 and βAR-2 inhibited the ISO response in Pkd2 +/− mice, suggesting that the dephosphorylated state of PLB is primarily by βAR-2 signaling. Importantly, the Pkd2 +/− mice were normotensive and had no evidence of renal cysts. Our results showed that decreased PC2 levels shifted the βAR pathway balance and changed expression of calcium handling proteins, which resulted in altered cardiac contractility. We propose that PC2 levels in the heart may directly contribute to cardiac remodeling in patients with ADPKD in the absence of renal dysfunction.calcium signaling | β-adrenergic receptor blocker | excitation contraction coupling

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The influence of the macroscale material properties of bone on its mechanical competence has been extensively investigated, but less is known about possible contributions from bone's nanoscale material properties. These nanoscale properties, particularly the collagen network and the size and shape of hydroxyapatite mineral crystals, may be affected by aging, mechanical loading, and diseases including osteoporosis. Here, changes to the collagen and mineral properties of cortical bone induced by osteoporosis and subsequent pharmaceutical treatments were investigated by simultaneous small- and wide-angle X-ray scattering (SAXS/WAXS) microbeam mapping. Adult rats (6 months old) were ovariectomized and treated with alendronate, parathyroid hormone, or sodium fluoride, and compared to untreated ovariectomized and age-matched controls. Scattering data from tibial cortical bone showed that osteoporosis increased collagen alignment in existing intracortical bone, while this effect was mitigated in the alendronate and sodium fluoride groups though by different mechanisms. Further, mineral crystal lengths in newly formed cortical bone were smaller in animals with osteoporosis, but existing cortical bone was not altered. Subsequent treatment with alendronate mitigated changes in crystal lengths. Together, these results suggest that osteoporosis may alter the collagen alignment and mineral geometry in bone formed before and after the onset of this disease, and that osteoporosis treatments may differentially rescue these changes.

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Electrical signals in excitable tissues such as nerves and muscles are generated by the synchronized opening and closing of ion channels in cell membranes, which generate transient transmembrane gradients in the concentrations of sodium and potassium ions. These channels open and close in response to local