Extracellular matrix plays a role in differentiation and phenotype development of its resident cells. Although cardiac extracellular matrix from the contractile tissues has been studied and utilized in tissue engineering, extracellular matrix properties of the pacemaking sinoatrial node are largely unknown. In this study, the biomechanical properties and biochemical composition and distribution of extracellular matrix in the sinoatrial node were investigated relative to the left ventricle. Extracellular matrix of the sinoatrial node was found to be overall stiffer than that of the left ventricle and highly heterogeneous with interstitial regions composed of predominantly fibrillar collagens and rich in elastin. The extracellular matrix protein distribution suggests that resident pacemaking cardiomyocytes are enclosed in fibrillar collagens that can withstand greater tensile strength while the surrounding elastin-rich regions may undergo deformation to reduce the mechanical strain in these cells. Moreover, basement membrane-associated adhesion proteins that are ligands for integrins were of low abundance in the sinoatrial node, which may decrease force transduction in the pacemaking cardiomyocytes. In contrast to extracellular matrix of the left ventricle, extracellular matrix of the sinoatrial node may reduce mechanical strain and force transduction in pacemaking cardiomyocytes. These findings provide the criteria for a suitable matrix scaffold for engineering biopacemakers.
Background Placenta accreta spectrum (PAS) in women with previous cesarean delivery has become increasingly prevalent. Depending on the severity, patient management may involve cesarean hysterectomy. Purpose To investigate textural analyses as the radiomics in MRI of the placenta in predicting the PAS requiring cesarean hysterectomy in a high‐risk population. Study Type Retrospective. Population Sixty‐two women with prior cesarean delivery referred for MRI because of sonographic suspicion for PAS. Field Strength/Sequence 1.5T with T1W, T2W, and diffusion‐weighted imaging (DWI). Assessment Two reviewers independently evaluated MR images based on five established PAS variables. Placental regions of interest (ROIs) were generated on T2W, DWI, and an apparent diffusion coefficient (ADC) map, based on definitions of areas of placenta in proximity to and remote from previous surgical incision sites. Statistical Tests Reader agreement was assessed by simple kappa and prevalence adjusted bias adjusted kappa (PABAK). T‐tests and chi‐square analyses between the primary outcome (hysterectomy vs. no hysterectomy) were performed. Thirteen Haralick texture features calculated from gray‐level co‐occurrence matrixes were extracted from manually drawn placental ROIs within each of three MR acquisitions. Univariate and multivariable logistic regression were used to assess the association with cesarean hysterectomy. Results Of 62 pregnancies at risk for PAS, 40 required cesarean hysterectomy (65%), with excellent correlation between need for hysterectomy and pathology confirmation of PAS in the hysterectomy specimen [κ = 0.82 (0.62, 1)]. Reader agreement was fair to moderate. Of the 13 Haralick variables within each of three acquisition groups, significant differences (P < 0.05) were seen in 22 of 39 parameters comparing placental ROIs in proximity to incision scar(s) to those ROIs remote from scar. A stepwise selection algorithm indicated that the combination of T2W Fcm.sum.var, ADC Fcm.diff.entr, and DWI Fcm.energy gave the highest leave‐one‐out‐AUC of 0.80 (0.68, 0.91). Data Conclusion Assessment of PAS severity is subjective and dependent on radiologist expertise. We identified textural features on placental MR images in the region of the prior uterine scar that differentiated pregnancies requiring cesarean hysterectomy based on clinical suspicion of PAS from those that did not, suggesting predictive capabilities of these objective radiomics features. Level of Evidence: 3 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;51:936–946.
Statins (e.g., simvastatin) have shown to induce expression of the bone morphogenic protein-2 gene in bone cells, but they are not used clinically because of a lack of a suitable delivery device. The overall objective is to develop optimized statin delivery devices for bone regeneration. The specific objective was to determine the effect of grafting statins to biodegradable poly[lactide-co-glycolide] (PLG) on release kinetics. Simvastatin was grafted to PLG (OG-PLG) and characterized using contact-angle measurements, attenuated total reflectance-Fourier transform infrared, and ultraviolet-visible spectroscopy to determine success of the synthesis. An ultraviolet-visible assay for measuring release of statins and degraded OG-PLG in media was also developed. In vitro release studies using films and scaffolds made with PLG, PLG blended with simvastatin (PLG + Sim), and OG-PLG (simvastatin grafted to PLG) blended into PLG at different concentrations showed that release rate of OG-PLG from films was significantly greater than that of PLG + Sim. However, release rate from scaffolds showed PLG + Sim to be significantly higher than that of OG-PLG. The diffusion-controlled release kinetics of simvastatin from PLG + Sim seems to be more heavily affected by device morphology, whereas the degradation-controlled release kinetics seem to be less affected. In short, release kinetics can be modulated by grafting statins to PLG.
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