Cardiac tissue engineering (CTE) aims to generate potential scaffolds to mimic extracellular matrix (ECM) for recreating the injured myocardium. Highly porous scaffolds with properties that aid cell adhesion, migration and proliferation are critical in CTE. In this study, electrospun porous poly (l-lactic acid) (PLLA) porous scaffolds were fabricated and modified with different ECM derived proteins such as collagen, gelatin, fibronectin and poly-L-lysine. Subsequently, adult human cardiac fibroblasts (AHCF) were cultured on the protein modified and unmodified fibers to study the cell behavior and guidance. Further, the cytotoxicity and reactive oxygen species (ROS) assessments of the respective fibers were performed to determine their biocompatibility. Excellent cell adhesion and proliferation of the cardiac fibroblasts was observed on the PLLA porous fibers regardless of the surface modifications. The metabolic rate of cells was on par with the conventional cell culture ware while the proliferation rate surpassed the latter by nearly two-folds. Proteome profiling revealed that apart from being an anchorage platform for cells, the surface topography has modulated significant expression of the cellular proteome with many crucial proteins responsible for cardiac fibroblast growth and proliferation.

Current conventional mono and combination therapeutic strategies often fail to target breast cancer tissue effectively due to tumor heterogeneity comprising cancer stem cells (CSCs) and bulk tumor cells. This is further associated with drug toxicity and resistivity in the long run. A nanomedicine platform incorporating combination anti-cancer treatment might overcome these challenges and generate synergistic anti-cancer effects and also reduce drug toxicity. GANT61 and curcumin were co-delivered via polymeric nanoparticles (NPs) for the first time to elicit enhanced anti-tumor activity against heterogeneous breast cancer cell line MCF-7. We adopted the single-emulsion-solvent evaporation method for the preparation of the therapeutic NPs. The GANT61-curcumin PLGA NPs were characterized for their size, shape and chemical properties, and anti-cancer cell studies were undertaken for the plausible explanation of our hypothesis. The synthesized GANT61-curcumin PLGA NPs had a spherical, smooth surface morphology, and an average size of 347.4 d. nm. The NPs induced cytotoxic effects in breast cancer cells at a midminimal dosage followed by cell death via autophagy and apoptosis, reduction in their target protein expression along with compromising the self-renewal property of CSCs as revealed by their in vitro cell studies. The dual-drug NPs thus provide a novel perspective on aiding existing anti-cancer nanomedicine therapies to target a heterogeneous tumor mass effectively.

Cardiovascular disease remains a major cause of deaths globally. Post heart infarction, the most abundant cell type of the heart, fibroblasts, undergo a series of culminating events that lead to fibrotic scar tissue. In many organisms, injury to the heart can be restored, but the adult human heart is unable to efficiently regenerate after ischemic injury. So, the inefficiency of the heart at regenerating on its own after ischemic injury accounts for its reprogramming. Herein, we demonstrate the effect of microRNAs encapsulating poly(lactic-co-glycolic acid) (PLGA)-polyethylenimine (PEI) nanocarriers for direct reprogramming of cardiac fibroblast to cardiomyocyte-like cells. Dual, cardiac-muscle-specific miRNA (miR-1 and miR-133a) polyplexes were encapsulated in biodegradable PLGA nanospheres. Cytocompatibility of the nanocomplexes were evaluated by various in vitro assays, confirming their safety profile. The change in cardiac fibroblast phenotype to cardiomyocyte was identified by the expression of late-stage signature markers. The PLGA-PEI-miRNA nanocomplex improved the intracellular internalization of cargo, exhibited pH-dependent release of the genetic material, and efficiently reprogrammed cardiac fibroblasts to cardiomyocyte-like cells. This is a first report of development of a nanovector targeting cardiac fibroblast for direct genetic reprogramming. Thus, this nanoscale approach serves as an ideal system for gene delivery and a promising therapeutic strategy for direct reprogramming of the heart.

Collagen-functionalized electrospun smooth and porous poly(l-lactide) scaffolds supporting keratinocytes and fibroblasts as a potential model to serve as self-organized skin substitute.