Injectable microbeads with a thermo-responsive shell and a pH-responsive core as a dual-switch-controlled release system.

Treating inflammation with a dual-switch-controlled release system: The release of a drug from the developed microbead system occurs only in response to both an increase in local temperature and an acidic environmental pH. This dual-switch-controlled release system has the advantages of distinguishing between inflamed and healthy tissues to improve treatment efficacy.

Electrical coupling of isolated cardiomyocyte clusters grown on aligned conductive nanofibrous meshes for their synchronized beating.

Myocardial infarction is often associated with abnormalities in electrical function due to a massive loss of functioning cardiomyocytes. This work develops a mesh, consisting of aligned composite nanofibers of polyaniline (PANI) and poly(lactic-co-glycolic acid) (PLGA), as an electrically active scaffold for coordinating the beatings of the cultured cardiomyocytes synchronously. Following doping by HCl, the electrospun fibers could be transformed into a conductive form carrying positive charges, which could then attract negatively charged adhesive proteins (i.e. fibronectin and laminin) and enhance cell adhesion. During incubation, the adhered cardiomyocytes became associated with each other and formed isolated cell clusters; the cells within each cluster elongated and aligned their morphology along the major axis of the fibrous mesh. After culture, expression of the gap-junction protein connexin 43 was clearly observed intercellularly in isolated clusters. All of the cardiomyocytes within each cluster beat synchronously, implying that the coupling between the cells was fully developed. Additionally, the beating rates among these isolated cell clusters could be synchronized via an electrical stimulation designed to imitate that generated in a native heart. Importantly, improving the impaired heart function depends on electrical coupling between the engrafted cells and the host myocardium to ensure their synchronized beating.

Recent advances in chitosan-based nanoparticles for oral delivery of macromolecules.

Chitosan (CS), a cationic polysaccharide, is widely regarded as a safe and efficient intestinal absorption enhancer of therapeutic macromolecules, owing to its inherent mucoadhesive feature and ability to modulate the integrity of epithelial tight junctions reversibly. By using CS-based nanoparticles, many studies have attempted to protect the loaded macromolecules against acidic denaturation and enzymatic degradation, prolong their intestinal residence time, and increase their absorption by the intestinal epithelium. Derivatives of CS such as quaternized CS, thiolated CS and carboxylated CS have also been examined to further enhance its effectiveness in oral absorption of macromolecular drugs. This review article describes the synthesis of these CS derivatives and their characteristics, as well as their potential transport mechanisms of macromolecular therapeutics across the intestinal biological membrane. Recent advances in using CS and its derivatives as carriers for oral delivery of hydrophilic macromolecules and their effects on drug transport are also reviewed.

Cardiac repair with injectable cell sheet fragments of human amniotic fluid stem cells in an immune-suppressed rat model.

Direct intramyocardial injection of the desired cell types in a dissociated form is a common route of cell transplantation for repair of damaged myocardium. However, following injection of dissociated cells, a massive loss of transplanted cells has been reported. In this study, human amniotic fluid stem cells (hAFSCs) were used as the cell source for the fabrication of cell sheet fragments, using a thermo-responsive methylcellulose hydrogel system. The fabricated hAFSC sheet fragments preserved the endogenous extracellular matrices (ECM) and retained their cell phenotype. Test samples were xenogenically transplanted into the peri-ischemic area of an immune-suppressed rat model at 1 week after myocardial infarction (MI) induction. There were four treatment groups (n>=10): sham; saline; dissociated hAFSCs; and hAFSC sheet fragments. The results obtained in the echocardiography revealed that the group treated with hAFSC sheet fragments had a superior heart function to those treated with saline or dissociated hAFSCs. Due to their inherent ECM, hAFSC sheet fragments had a better ability of cell retention and proliferation than dissociated hAFSCs upon transplantation to the host myocardium. Additionally, transplantation of hAFSC sheet fragments stimulated a significant increase in vascular density, consequently contributing towards improved wall thickness and a reduction in the infarct size, when compared with dissociated hAFSCs. Our histological findings and qPCR analyses suggest that the transplanted hAFSCs can be differentiated into cardiomyocyte-like cells and cells of endothelial lineages and modulate expression of multiple angiogenic cytokines and cardiac protective factor with the potential to promote neo-vascularization, which evidently contributed to the improvement of ventricular function.

Cellular cardiomyoplasty with human amniotic fluid stem cells: in vitro and in vivo studies.

Human amniotic fluid stem cells (hAFSCs) derived from second-trimester amniocentesis were evaluated for the therapeutic potential of cardiac repair. Whether hAFSCs can be differentiated into cardiomyogenic cells and toward the maturation of endothelial cell lineage was investigated in vitro using mimicking differentiation milieu. Employing an immune-suppressed rat model with experimental myocardial infarction, an intramyocardial injection was conducted with a needle directly into the peri-infarct areas. There were three treatment groups: sham, saline, and hAFSCs (n > or = 10). When cultured with rat neonatal cardiomyocytes or in endothelial growth medium-2 enriched with vascular endothelial growth factor, hAFSCs were differentiated into cardiomyocyte-like cells and cells of endothelial lineage, respectively. After 4 weeks, hAFSC-treated animals showed a preservation of the infarcted thickness, an attenuation of left ventricle remodeling, a higher vascular density, and thus an improvement in cardiac function, when compared with the saline injection group. Survival and proliferation of the transplanted hAFSCs were revealed by immunohistochemical staining. Expressions of the cardiac-specific markers such as Nkx2.5, alpha-actinin, and cardiac Troponin T were observed in the transplanted hAFSCs. Additionally, Cx43 was clearly expressed at the borders of the transplanted/transplanted and host/transplanted cells, an indication of enhancement of cell connection. The results demonstrated that hAFSCs induce angiogenesis, have cardiomyogenic potential, and may be used as a new cell source for cellular cardiomyoplasty.