Recently, biomedicine and tissue regeneration have emerged as great advances that impacted the spectrum of healthcare. This left the door open for further improvement of their applications to revitalize the impaired tissues. Hence, restoring their functions. The implementation of therapeutic protocols that merge biomimetic scaffolds, bioactive molecules, and cells plays a pivotal role in this track. Smart/stimuli-responsive hydrogels are remarkable three-dimensional (3D) bioscaffolds intended for tissue engineering and other biomedical purposes. They can simulate the physicochemical, mechanical, and biological characters of the innate tissues. Also, they provide the aqueous conditions for cell growth, support 3D conformation, provide mechanical stability for the cells, and serve as potent delivery matrices for bioactive molecules. Many natural and artificial polymers were broadly utilized to design these intelligent platforms with novel advanced characteristics and tailored functionalities that fit such applications. In the present review, we highlighted the different types of smart/stimuli-responsive hydrogels with emphasis on their synthesis scheme. Besides, the mechanisms of their responsiveness to different stimuli were elaborated. Their potential for tissue engineering applications was discussed. Furthermore, their exploitation in other biomedical applications as targeted drug delivery, smart biosensors, actuators, 3D and 4D printing, and 3D cell culture were outlined. In addition, we threw light on smart self-healing hydrogels and their applications in biomedicine. Eventually, we presented their future perceptions in biomedical and tissue regeneration applications. Conclusively, current progress in the design of smart/stimuli-responsive hydrogels enhances their prospective to function as intelligent, and sophisticated systems in different biomedical applications.

Background: The effects of pimobendan on left atrial pressure (LAP) in dogs with mitral valve disease (MR) have not been documented in a quantitative manner.Objective: The objective was to document and study the short-term effects of pimobendan on LAP and echocardiographic parameters in MR dogs.Animals: Eight healthy Beagle dogs weighing 10.0-14.7 kg (3 males and 5 females; aged 2 years) were used. Methods: Experimental, cross-over, and interventional study. Dogs with surgically induced MR received pimobendan at either 0.25 mg/kg or 0.50 mg/kg PO q12h for 7 days and then, after a 7-day wash-out period, the other dosage. LAP was measured for 30 minutes at baseline and again on days 1, 2, 4, and 7 of pimobendan administration.Results: Mean LAP was significantly decreased after the administration of 0.25 mg/kg (15.81 ± 5.44 mmHg to 12.67 ± 5.71 mmHg, P < .001) and 0.50 mg/kg (15.76 ± 5.45 mmHg to 10.77 ± 5.23 mmHg, P < .001). Also, the 0.50 mg/ kg group led to a significantly lower LAP (P < .01) compared with the 0.25 mg/kg group. Significant reduction was seen for the first time 4 days after the administration of 0.25 mg/kg and a day after the administration of 0.50 mg/kg.Conclusions and Clinical Importance: Pimobendan decreased LAP in a dose-dependent manner in dogs with acute MR caused by experimental chordal rupture. This study did not evaluate adverse effects of high-dose pimobendan, and additional studies in clinical patients are warranted.

The double-chambered right ventricle (DCRV) is a rare congenital cardiac disease in dogs, and its detailed epidemiological and morphological features are not clearly understood. By investigating the profile, clinical signs, and characteristics of examination findings of eleven dogs with DCRV by means of a retrospective study, we attempted to clarify the epidemiology and morphology of the condition. The study group consisted of nine males and two females. Breeds included Pug (n=3), Miniature Dachshund (n=1), French Bull-dog (n=1), Shiba (n=1), and Retrievers (n=5). The attachment site of the anomalous muscular bundle was continuous with the cardiac apex in nine dogs, and it was attached to the right ventricle free wall in the other two dogs. In dogs with DCRV, at least one of the following conditions was present concurrently: congenital or acquired tricuspid valve regurgitation (TR), ventricular septal defect, and atrial septal defect. Also, the pressure difference between the two chambers increased over time, and progressive right-sided heart failure was observed. In summary, DCRV occurs in small breeds of dog as well as in large breeds of dog and it may be more prevalent in males. The existence of two types of DCRV in dogs was established. Dog with DCRVs will have a high incidence of concurrent cardiac abnormalities. Concurrent TR may be either congenital or acquired. DCRV is a congenital disorder, but the clinical condition progresses as the dog develops.

Evaluation of diastolic function is a pivotal challenge due to limitations of the conventional echocardiography, especially when the heart rate is rapid as in rats. Currently, by using color M-mode echocardiography (CMME), intraventricular pressure difference (IVPD) and intraventricular pressure gradient (IVPG) in early diastole can be generated and are available as echocardiographic indices. These indices are expected to be useful for the early diagnosis of heart failure (HF), especially diastolic dysfunction. There have not been any studies demonstrating changes in IVPD and IVPG in response to changes in loading conditions in rats. Therefore, the present study aims to evaluate CMME-derived IVPD and IVPG changes in rats under various loading conditions. Twenty rats were included, divided into two groups for two different experiments, and underwent jugular vein catheterization under inhalational anesthetics. Conventional echocardiography, CMME, and 2D speckle tracking echocardiography were measured at the baseline (BL), after intravenous infusion of milrinone (MIL, n = 10), and after the infusion of hydroxyethyl starch (HES, n = 10). Left ventricular IVPD and IVPG were calculated from color M-mode images and categorized into total, basal, mid-to-apical, mid, and apical parts, and the percentage of the corresponding part was calculated. In comparison to the BL, the ejection fraction, mid-to-apical IVPG, mid IVPG, and apical IVPD were significantly increased after MIL administration (p < 0.05); meanwhile, the end-diastolic volume, E-wave velocity, total IVPD, and basal IVPD were significantly increased with the administration of HES (p < 0.05). The increase in mid-to-apical IVPD, mid IVPD, and apical IVPD indicated increased relaxation. A significant increase in basal IVPD reflected volume overloading by HES. CMME-derived IVPD and IVPG are useful tools for the evaluation of various loading conditions in rats. The approach used in this study provides a model for continuous data acquisition in chronic cardiac disease models without drug testing.

BackgroundOne of the purposes of treatment for dogs with mitral regurgitation (MR) is lowering left atrial pressure (LAP). There has been few study of the amlodipine in dogs with MR and amlodipine’s effect on LAP has not been fully evaluated in a quantitative manner because of difficulties in directly measuring LAP. The objective of our study was to compare the short-term effects of amlodipine (0.2 mg/kg PO q12h) vs benazepril (0.5 mg/kg PO q12h), on LAP and echocardiographic parameters in five beagle dogs with experimentally-induced MR. LAP of eight dogs that has own control were measured using radiotelemetry system at baseline and again on days 1, 2, 3, 4, 5, 6, 7 of the drug administration.ResultsMean LAP decreased significantly after amlodipine (11.20 ± 4.19 mmHg vs 14.61 ± 3.81 mmHg at baseline, p < .01) but not after benazepril treatment (13.19 ± 3.47 mmHg, p > .05). LAP was lower after 7 days of amlodipine treatment than after 7 days of benazepril treatment. Significant reduction was seen for the first time 4 days after the administration amlodipine. The rate of the maximal area of the regurgitant jet signals to the left atrium area (ARJ/LAA) of the amlodipine treatment was significantly lower (p < .05) after 7 days compared to baseline. Other echocardiographic parameters did not change significantly.ConclusionsLAP was significantly decreased after amlodipine treatment in dogs with surgically-induced MR but not after benazepril treatment. Although this study did not focus on adverse effects, amlodipine may be an effective drug for helping the patients with acute onset of severe MR, such as rupture of chordae tendinae or end stage patients were the LAP is likely to be elevated. Additional studies in clinical patients with degenerative mitral valve disease and acute chordal rupture are warranted because the blood-pressure lowering effects of amlodipine can decrease renal perfusion and this can further activate the RAAS.