Exercise-induced CITED4 expression is necessary for regional remodeling of cardiac microstructural tissue helicity.

Both exercise-induced molecular mechanisms and physiological cardiac remodeling have been previously studied on a whole heart level. However, the regional microstructural tissue effects of these molecular mechanisms in the heart have yet to be spatially linked and further elucidated. We show in exercised mice that the expression of CITED4, a transcriptional co-regulator necessary for cardioprotection, is regionally heterogenous in the heart with preferential significant increases in the lateral wall compared with sedentary mice. Concordantly in this same region, the heart's local microstructural tissue helicity is also selectively increased in exercised mice. Quantification of CITED4 expression and microstructural tissue helicity reveals a significant correlation across both sedentary and exercise mouse cohorts. Furthermore, genetic deletion of CITED4 in the heart prohibits regional exercise-induced microstructural helicity remodeling. Taken together, CITED4 expression is necessary for exercise-induced regional remodeling of the heart's microstructural helicity revealing how a key molecular regulator of cardiac remodeling manifests into downstream local tissue-level changes.

Fabrication and Evaluation of Polycaprolactone Beads-on-String Membranes for Applications in Bone Tissue Regeneration.

Tissue engineering leads to the development of biomaterial scaffolds where its biocompatibility and bioactivity are often improved after performing physical or chemical surface modification treatments. Micropatterning, soft lithography, and biofabrication are also approaches that provide a biomimetic microenvironment but have proven very costly and time consuming. In this concern, an appropriate substrate with suitable sites for cell attachment represents a major factor in cell behavior and biological functions. For this reason, our strategy was to fabricate a standard fibrous biomaterial with reproducible surface topography, incorporating microbeads and nanofeatures, and show the positive outcomes of the new substrate reflected on cell functions of bone cells. The electrospun polycaprolactone (PCL) beads-on-string membranes were obtained by adjusting the spinning solution at different concentrations until continuous beads were formed. Cell adhesion and proliferation, on the PCL scaffold, were analyzed the subsequent 2 days after initial culture. Complementary studies of cytoskeleton spreading and differentiation were analyzed after 7 and 14 days of the initial incubation. The scanning electron microscopy (SEM) images showed evidence of the formation of beads-on-string nanofibers and suggested that as-formed microstructures worked as attachment sites for osteoblasts. We investigated cell proliferation using anti-BrdU fluorescence assay, and results show a similar proliferation rate of cells cultured between PCL scaffolds and control. Finally, Phalloidin TRITC and antisialoprotein antibody were used to analyze cell spreading and differentiation after 7 and 14 days, respectively. This work shows a low-cost fabrication method to produce a biodegradable scaffold with micro/nanostructured characteristics that favor cell adhesion, proliferation, maturation, and subsequent differentiation of osteoblasts. According to the results, the biocompatibility of PCL beads-on-string could be comparable to other complex biomaterials, and we conclude that our scaffold is optimal for applications in bone tissue regeneration.