Phosphorylcholine-Based Zwitterionic Biocompatible Thermogel.

Zwitterionic polymers have been investigated as surface-coating materials due to their low protein adsorption properties, which reduce immunogenicity, biofouling, and bacterial adsorption of coated materials. Most zwitterionic polymers, reported so far, are based on (meth)acrylate polymers which can induce toxicity by residual monomers or amines produced by degradation. Here, we report a new zwitterionic polymer consisting of phosphorylcholine (PC) and biocompatible poly(propylene glycol) (PPG) as a new thermogelling material. The PC-PPG-PC polymer aqueous solution undergoes unique multiple sol-gel transitions as the temperature increases. A heat-induced unimer-to-micelle transition, changes in ionic interactions, and dehydration of PPG are involved in the sol-gel transitions. Based on the broad gel window and low protein adsorption properties, the PC-PPG-PC thermogel is proved for sustained delivery of protein drugs and stem cells over 1 week.

Relative importance of left atrial reservoir strain compared with components of the HFA-PEFF score: a cross-sectional study.

Background: The relative importance of left atrial reservoir strain (LASr) regarding the Heart Failure Association Pre-test assessment, Echocardiography and natriuretic peptide, Functional testing, Final etiology (HFA-PEFF) score, a diagnostic tool for patients with heart failure with preserved ejection fraction (HFpEF), remains unclear. We aimed to identify the relative importance of LASr compared with variables associated with HFpEF and HFA-PEFF scores. Methods: Between August 2021 and July 2022, we obtained retrospective data from the participants visiting a single cardiovascular center with subjective symptoms of heart failure, such as dyspnea or chest discomfort. In total, 2,712 participants with sinus rhythm and ejection fraction of more than 50% were enrolled. Multivariable logistic regression analysis, random forest analysis, and supervised machine learning algorithms were performed to identify the relative importance of LASr to the HFA-PEFF score. Results: The average HFA-PEFF score was 2.4 ± 1.6 points. Two hundred and thirty-eight participants had 5 or 6 points. LASr showed a moderate correlation with the HFA-PEFF score (r = -0.50, p < 0.001). Impaired LASr < 25.2% was an independent variable affecting a high HFA-PEFF score with traditional diastolic function parameters and components of the HFA-PEFF diagnostic algorithm. The odds ratio (OR) [1.74, 95% confidence interval (CI) 1.23-2.47] for LASr was higher compared to that of left ventricular global longitudinal strain (OR 1.59, 95% CI 1.14-2.21), septal E/e' (OR 1.23, 95% CI 0.85-1.77), and relative wall thickness (OR 1.20, 95% CI 0.76-1.89). LASr was also a relatively more important variable in estimating a high HFA-PEFF score than TR-Vmax, septal E/e', septal e', left ventricular mass index, and relative wall thickness, the major echocardiographic components of the HFA-PEFF score. Conclusions: LASr is an important factor with components of the HFA-PEFF score and is a useful tool to assess patients with HFpEF. Clinical Trial Registration: URL: https://clinicaltrials.org. Unique identifiers: NCT05638230.

Left Ventricular Global Longitudinal Strain as a Predictor for Left Ventricular Reverse Remodeling in Dilated Cardiomyopathy.

BACKGROUND: A considerable number of patients with dilated cardiomyopathy (DCM) experience left ventricular reverse remodeling (LVRR). LV global longitudinal strain (LV GLS) offers sensitive and reproducible measurement of myocardial dysfunction. The authors sought to evaluate whether LV GLS at the time of diagnosis may predict LVRR in DCM patients with sinus rhythm and investigate its prognostic role in long-term follow-up in this population. METHODS: We enrolled 160 DCM patients with sinus rhythm who had been initially diagnosed, evaluated, and followed at our institute. We analyzed their medical records and echocardiographic data. RESULTS: During the mean follow-up duration of 37.3 ± 21.7 months, LVRR occurred in 28% of patients (n = 45). The initial LV ejection fraction (LVEF) of patients who recovered LV function was 26.1 ± 7.9%, which was not significantly different from the value of 27.1 ± 7.4% (p = 0.49) in those who did not recover. There was a moderate and highly significant correlation between baseline LV GLS (-%) and follow-up LVEF (r = 0.717; p < 0.001). Using multivariate Cox analysis, LV GLS (hazard ratio: 1.474, 95% confidence interval: 1.170-1.856; p = 0.001) was an independent predictor of LVRR. CONCLUSIONS: We demonstrated that LV GLS was an independent predictor for LVRR and the optimal cut-off point of LV GLS for LVRR was -10% in DCM patients with sinus rhythm. There was a significant correlation between baseline LV GLS and follow-up LVEF.

The prognostic value of 2D strain in assessment of the right ventricle in patients with dilated cardiomyopathy.

AIMS: Several studies have been reported using right ventricular (RV) strain as a method for evaluating RV function in patients with various cardiovascular diseases; however, the clinical relevance of RV strain in dilated cardiomyopathy (DCM) patients with sinus rhythm is unknown. The aim of this study was to investigate the relationship between RV strain and adverse events in DCM patients with sinus rhythm. METHODS AND RESULTS: We enrolled 143 DCM patients with sinus rhythm who had been first diagnosed, evaluated, and followed at Sanggye Paik Hospital between March 2013 and August 2017. We performed echocardiography and measured RV strain values using the apical four-chamber view. The mean age was 64.6 years. During the median follow-up period of 40.0 months, adverse cardiovascular events developed in 21 patients (14.7%). By Cox proportional hazards multivariate analysis, only RV free wall longitudinal strain (RV-FWLS) independently predicted the primary outcome. Receiver-operating characteristic curve analysis showed that the optimal RV-FWLS cut-off value to identify patients with an event was -16.5% (area under the curve = 0.703, P = 0.003). When we divided the subjects into two groups based on the RV-FWLS of -16.5%, patients with RV-FWLS <-16.5% showed more favourable clinical outcomes than that in those with RV-FWLS ≥-16.5% (log-rank test, P < 0.001). CONCLUSION: RV-FWLS was associated with a significant prognostic impact in DCM patients with sinus rhythm.

PEG-Poly(L-alanine) thermogel as a 3D scaffold of bone-marrow-derived mesenchymal stem cells.

Bone-marrow-derived mesenchymal stem cells (BMSCs) were cultured in three-dimensional (3D) scaffolds formed by temperature-sensitive sol-to-gel transition of BMSC-suspended poly(ethylene glycol)-poly(L-alanine) (PEG-PA) aqueous solutions. A commercialized thermogelling 3D scaffold of Matrigel™ was used for the comparative study. The cells maintained their spherical shapes in the PEG-PA thermogel, whereas fibrous cell morphologies were observed in the Matrigel™. Type II collagen and myogenic differentiation factor 1 were dominantly expressed in the PEG-PA thermogel. On the other hand, a significant extent of type III ß-tubulin was expressed in the Matrigel™ in addition to type II collagen and myogenic differentiation factor 1. After confirming the dominant chondrogenic differentiation of the BMSCs in the PEG-PA thermogel in in vitro study, in vivo study was performed for injectable tissue engineering application of the BMSCs/PEG-PA system. The cell-growing implant was formed in situ by subcutaneous injection of the BMSC-suspended PEG-PA aqueous solution to mice. In vivo study also proved the excellent expressions of chondrogenic biomarkers including collagen type II and sulfated glycosaminoglycan in the mouse model. This paper suggests that the PEG-PA thermogel is a very promising as a 3D culture matrix as well as an injectable tissue-engineering system for preferential chondrogenic differentiation of the BMSCs.

Polypeptide thermogels as a three dimensional culture scaffold for hepatogenic differentiation of human tonsil-derived mesenchymal stem cells.

Tonsil-derived mesenchymal stem cells (TMSCs) were investigated for hepatogenic differentiation in the 3D matrixes of poly(ethylene glycol)-b-poly(l-alanine) (PEG-L-PA) thermogel. The diblock polymer formed ß-sheet based fibrous nanoassemblies in water, and the aqueous polymer solution undergoes sol-to-gel transition as the temperature increases in a concentration range of 5.0-8.0 wt %. The cell-encapsulated 3D matrix was prepared by increasing the temperature of the cell-suspended PEG-L-PA aqueous solution (6.0 wt %) to 37 °C. The gel modulus at 37 °C was about 1000 Pa, which was similar to that of decellularized liver tissue. Cell proliferation, changes in cell morphology, hepatogenic biomarker expressions, and hepatocyte-specific biofunctions were compared for the following 3D culture systems: TMSC-encapsulated thermogels in the absence of hepatogenic growth factors (protocol M), TMSC-encapsulated thermogels where hepatogenic growth factors were supplied from the medium (protocol MGF), and TMSC-encapsulated thermogels where hepatogenic growth factors were coencapsulated with TMSCs during the sol-to-gel transition (protocol GGF). The spherical morphology and size of the encapsulated cells were maintained in the M system during the 3D culture period of 28 days, whereas the cells changed their morphology and significant aggregation of cells was observed in the MGF and GGF systems. The hepatocyte-specific biomarker expressions and metabolic functions were negligible for the M system. However, hepatogenic genes of albumin, cytokeratin 18 (CK-18), and hepatocyte nuclear factor 4α (HNF 4α) were significantly expressed in both MGF and GGF systems. In addition, production of albumin and α-fetoprotein was also significantly observed in both MGF and GGF systems. The uptake of cardiogreen and low-density lipoprotein, typical metabolic functions of hepatocytes, was apparent for MGF and GGF. The above data indicate that the 3D culture system of PEG-L-PA thermogels provides cytocompatible microenvironments for hepatogenic differentiation of TMSCs. In particular, the successful results of the GGF system suggest that the PEG-L-PA thermogel can be a promising injectable tissue engineering system for liver tissue regeneration after optimizing the aqueous formulation of TMSCs, hepatogenic growth factors, and other biochemicals.