Nanocomposite hydrogels: an emerging biomimetic platform for myocardial therapy and tissue engineering

Recent years have seen a significant rise in patient survival rate after myocardial infarction, commonly known as heart attack. This is mainly due to improvement in hospital instrument facilities, clinical management system, surgical tools and technologies. However, many of these patients soon develop heart failure, with 50% mortality rate within 5 years of heart attack [1]. As the regeneration power of the heart muscle is very limited, negative remodeling and nonfunctional scar tissue deposition leads to gradual terminal failure of the heart. Current treatments include heart transplantation and ventricular assist devices, which are both highly invasive and risky surgical procedures with inconsistent results. Stem cell transplantation has recently shown some potential that can improve heart function through several mechanisms such as cardiac differentiation, neoangiogenesis and paracrine effects [2]. Despite promising results, stem cell therapy still remains limited because of economic, timing and logistic issues, particularly when isolating cells from elderly patients under clinical settings. Reduced cell survival and retention at the transplant site further limits their therapeutic potential [3]. Thus, we see an urgent need for new strategies to attenuate the progression of the disease postmyocardial infarction. The following sections highlight the emerging roles of biocompatible nanomaterials and hydrogels and provide insights for further development in cardiac therapy and tissue engineering applications

Diet-induced metabolic hamster model of nonalcoholic fatty liver disease

Obesity, hypercholesterolemia, elevated triglycerides, and type 2 diabetes are major risk factors for metabolic syndrome. Hamsters, unlike rats or mice, respond well to diet-induced obesity, increase body mass and adiposity on group housing, and increase food intake due to social confrontation-induced stress. They have a cardiovascular and hepatic system similar to that of humans, and can thus be a useful model for human pathophysiology

A multilayered microfluidic blood vessel-like structure

There is an immense need for tissue engineered blood vessels. However, current tissue engineering approaches still lack the ability to build native blood vessel-like perfusable structures with multi-layered vascular walls. This paper demonstrated a new method to fabricate tri-layer biomimetic blood vessel-like structures on a microfluidic platform using photocrosslinkable gelatin hydrogel. The presented method enables fabrication of physiological blood vessel-like structures with mono-, bi- or tri-layer vascular walls. The diameter of the vessels, the total thickness of the vessel wall and the thickness of each individual layer of the wall were independently controlled. The developed fabrication process is a simple and rapid method, allowing the physical fabrication of the vascular structure in minutes, and the formation of a vascular endothelial cell layer inside the vessels in 3–5 days. The fabricated vascular constructs can potentially be used in numerous applications including drug screening, development of in vitro models for cardiovascular diseases and/or cancer metastasis, and study of vascular biology and mechanobiology.American University of Beirut (startup grant and University Research Board grant)National Council for Scientific Research (Lebanon)National Science Foundation (U.S.) (EFRI-1240443)Immodgel (602694)National Institutes of Health (U.S.) (EB012597, AR057837, DE021468, HL099073, AI105024, AR063745)National Institute of General Medical Sciences (U.S.) ( Award Number P20GM103638-04)King Abdulaziz City for Science and Technology (Grant No. 12-MED3096-3

Cationic Albumin Nanoparticles for Enhanced Drug Delivery to Treat Breast Cancer: Preparation and In Vitro Assessment

Most anticancer drugs are greatly limited by the serious side effects that they cause. Doxorubicin (DOX) is an antineoplastic agent, commonly used against breast cancer. However, it may lead to irreversible cardiotoxicity, which could even result in congestive heart failure. In order to avoid these harmful side effects to the patients and to improve the therapeutic efficacy of doxorubicin, we developed DOX-loaded polyethylenimine- (PEI-) enhanced human serum albumin (HSA) nanoparticles. The formed nanoparticles were ~137 nm in size with a surface zeta potential of ~+15 mV, prepared using 20 μg of PEI added per mg of HSA. Cytotoxicity was not observed with empty PEI-enhanced HSA nanoparticles, formed with low-molecular weight (25 kDa) PEI, indicating biocompatibility and safety of the nanoparticle formulation. Under optimized transfection conditions, approximately 80% of cells were transfected with HSA nanoparticles containing tetramethylrhodamine-conjugated bovine serum albumin. Conclusively, PEI-enhanced HSA nanoparticles show potential for developing into an effective carrier for anticancer drugs

Deciphering the role of substrate stiffness to enhance internalization efficiency of plasmid DNA in stem cells using lipid-based nanocarriers

This study investigates the role of substrate stiffness on non-viral transfection of human adipose-derived stem cells (hASCs) with the aim to maximize hASCs expression of vascular endothelial growth factor (VEGF). The results confirm the direct effect of substrate stiffness in regulating cytoskeletal remodeling and corresponding plasmid internalization

Cationic Albumin Nanoparticles for Enhanced Drug Delivery to Treat Breast Cancer: Preparation and In Vitro Assessment

Most anticancer drugs are greatly limited by the serious side effects that they cause. Doxorubicin (DOX) is an antineoplastic agent, commonly used against breast cancer. However, it may lead to irreversible cardiotoxicity, which could even result in congestive heart failure. In order to avoid these harmful side effects to the patients and to improve the therapeutic efficacy of doxorubicin, we developed DOX-loaded polyethylenimine- (PEI-) enhanced human serum albumin (HSA) nanoparticles. The formed nanoparticles were ~137 nm in size with a surface zeta potential of ~+15 mV, prepared using 20 μg of PEI added per mg of HSA. Cytotoxicity was not observed with empty PEI-enhanced HSA nanoparticles, formed with low-molecular weight (25 kDa) PEI, indicating biocompatibility and safety of the nanoparticle formulation. Under optimized transfection conditions, approximately 80% of cells were transfected with HSA nanoparticles containing tetramethylrhodamine-conjugated bovine serum albumin. Conclusively, PEI-enhanced HSA nanoparticles show potential for developing into an effective carrier for anticancer drugs

Mitotic and antiapoptotic effects of nanoparticles coencapsulating human VEGF and human angiopoietin-1 on vascular endothelial cells

Research towards the application of nanoparticles as carrier vehicles for the delivery of therapeutic agents is increasingly gaining importance. The angiogenic growth factors, human vascular endothelial growth factor (VEGF) and human angiopoietin-1 are known to prevent vascular endothelial cell apoptosis and in fact to stimulate human vascular endothelial cell (HUVEC) proliferation. This paper aims to study the combined effect of these bioactive proteins coencapsulated in human serum albumin nanoparticles on HUVECs and to evaluate the potential application of this delivery system towards therapeutic angiogenesis

Suppression of Tumorigenesis: Modulation of Inflammatory Cytokines by Oral Administration of Microencapsulated Probiotic Yogurt Formulation

The objective of this study was to examine the ability of a novel microencapsulated probiotic yogurt formulation to suppress the intestinal inflammation. We assessed its anticancer activity by screening interleukin-1, 6, and 12 (IL-1, 6, 12), secretory levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), prostaglandin E2  (PGE2), and thromboxane B2 in the digesta obtained from the duodenum, jejunum, proximal, and distal segments of the ileum of C57BL/6J-ApcMin/J mice. Formulation-receiving animals showed consistently lower proinflammatory cytokines' levels when compared to control group animals receiving empty alginate-poly-L-lysine-alginate (APA) microcapsules suspended in saline. The concentrations of IL-12 found in serum in control and treatment group animals were significant: 46.58 ± 16.96 pg/mL and 158.58 ± 28.56 pg/mL for control and treatment animals, respectively. We determined a significant change in plasma C-reactive protein: 81.04 ± 23.73 ng/mL in control group and 64.21 ± 16.64 ng/mL in treatment group. Western blots showed a 71% downregulation of cyclooxygenase-2 (COX-2) protein in treatment group animals compared to control. These results point to the possibility of using this yogurt formulation in anticancer therapies, in addition to chronic gut diseases such as Crohn's disease, irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD) thanks to its inflammation lowering properties