Due to its regenerative potential, hyaluronic acid-based hydrogel provides a promising novel therapy to be used alone, or as a scaffold delivering a variety of drugs or cells to combat heart disease in a multifaceted approach.
Injectable hydrogels are extensively used in drug delivery and tissue engineering to administer drugs, genes, growth factors and live cells. We report a method to produce tough, in-situ thermogelling, non-toxic, injectable hydrogels made of chitosan and hyaluronic acid co-crosslinked with β-glycerophophate and genipin. The gels are highly homogeneous and form within 32 min, i.e., faster than gels crosslinked with either genipin or β-glycerophophate. The shear strength of co-crosslinked hydrogels is 3.5 kPa, higher than any chitosan-based gel reported. Chondrocytes and nucleus pulposus cells thrive inside the gels and produce large amounts of collagen II. Injection in rats shows that the gels form in-vivo within a short time and remain well localized for more than one week while the rats remain healthy and active. The excellent mechanical properties, fast in-situ gelation, good biocompatibility and the ability to encapsulate live cells at physiological conditions make these hydrogels ideal for tissue engineering, especially cartilage regeneration.
Introduction: Heart failure with reduced ejection fraction (HFrEF) exhibits exaggerated sympathoexcitation and altered cardiac and vascular responses to muscle metaboreflex activation (MMA). However, left ventricular (LV) responses to MMA are not well studied in patients with HFrEF. The purpose of this study was to examine LV function during MMA using cardiac magnetic resonance imaging (MRI) in patients with HFrEF. Methods: Thirteen patients with HFrEF and 18 healthy age-matched controls underwent cardiac MRI during rest and MMA. MMA protocol included 6-min of isometric handgrip exercise followed by 6-min of brachial post-exercise circulatory occlusion. LV stroke volume index (SVi), end-systolic volume index (ESVi), end-diastolic volume index (EDVi) and global longitudinal strain (GLS) were measured by 2- and 4-chamber cine images. Volumes were indexed to body surface area. Heart rate (via ECG) and brachial mean arterial pressure (MAP) were recorded. Cardiac output and total peripheral resistance (TPR) were calculated. Results: SVi decreased during MMA in HFrEF (P=0.037) but not controls (P=0.392). ESVi (P=0.007) and heart rate (P<0.001) increased during MMA in HFrEF but not controls (P≥0.170). TPR (P=0.021) and MAP (P<0.001) increased during MMA in both groups. Cardiac output (P=0.946), EDVi (P=0.177), and GLS (P=0.619) were maintained from rest to MMA in both groups. Conclusions: Despite similarly maintained cardiac output, LV strain, and increased TPR in HFrEF and control groups, SVi decreased, and heart rate increased during MMA in patients with HFrEF. These findings suggest an impaired contractility reserve in response to increased TPR during MMA in HFrEF.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.