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The endothelialization of prosthetic scaffolds is considered to be an effective strategy to improve the effectiveness of small-diameter vascular grafts. We report the development of a nanofibrous scaffold that has a polymeric core and a shell mimicking mussel adhesive for enhanced attachment, proliferation, and phenotypic maintenance of human endothelial cells. Polycaprolactone (PCL) was chosen as a core material because of its good biodegradability and mechanical properties suitable for tissue engineering. PCL was electrospun into nanofibers with a diameter of approximately 700 nm and then coated with poly(dopamine) (PDA) to functionalize the surface of PCL nanofibers with numerous catechol moieties similar to mussel adhesives in nature. The formation of a PDA ad-layer was analyzed using multiple techniques, including scanning electron microscopy, Raman spectroscopy, and water contact angle measurements. When PDA-coated PCL nanofibers were compared to unmodified and gelatin-coated nanofibers, human umbilical vein endothelial cells (HUVECs) exhibited highly enhanced adhesion and viability, increased stress fiber formation, and positive expression of endothelial cell markers (e.g., PECAM-1 and vWF).

Amyloid-beta (Abeta) is the major constituent of senile plaques in the brains of Alzheimer's disease patients. In order to develop an efficient in vitro system for studying the interaction of cells with Abeta aggregates, we have prepared a synthetic amyloid lawn by immobilizing Abeta peptides over a functionalized glass surface and subsequently incubating the template in a fresh Abeta solution. On the top of different types of amyloid lawns (e.g. monomeric, oligomeric, and fibrillar), we cultivated PC12 cells, creating physical contacts between the cells and the lawns. Results indicated that cell viability was differentially affected when grown atop different Abeta lawns while cells were well adhered onto the surface of these Abeta lawns. The mode of cell death by Abeta lawn was confirmed to be apoptotic rather than necrotic, showing that cells undergo suicide by just contact with Abeta lawn. While conventional 'solution-based' methods for testing amyloid toxicity suffer from problems such as lot-to-lot variations, continued fibrillation, and heterogeneous population of aggregates, our 'surface-based' lawn system is suitable for high-throughput analysis of amyloid toxicity, which may enable high-throughput screening of potential drug candidates for treating amyloid diseases with the goal of reducing the cell death on the lawn.

Inflammatory response in myocardial ischemia-reperfusion injury plays a critical role in ventricular remodeling. To avoid deleterious effects of overwhelming inflammation, we blocked the expression of receptor for advanced glycation end-products (RAGE), a key mediator of the local and systemic inflammatory responses, via RNAi mechanism. Herein, a facial amphipathic deoxycholic acid-modified low molecular weight polyethylenimine (DA-PEI) was used as a siRNA delivery carrier to myocardium. The DA-PEI conjugate formed a stable complex with siRNA via electrostatic and hydrophobic interactions. The siRAGE/DA-PEI formulation having negligible toxicity could enhance intracellular delivery efficiency and successfully suppress RAGE expression both in vitro and in vivo. Furthermore, the cardiac administration of siRAGE/DA-PEI reduced apoptosis and inflammatory cytokine release, subsequently led to attenuation of left ventricular remodeling in rat myocardial infarction model. The potential therapeutic effects of RAGE gene silencing on myocardial ischemia-reperfusion injury may suggest that the siRAGE/DA-PEI delivery system can be considered as a promising strategy for treating myocardial infarction.

Graphene-based nanomaterials have received much attention in biomedical applications for drug/gene delivery, cancer therapy, imaging, and tissue engineering. Despite the capacity of 2D carbon materials as a nontoxic and implantable platform, their effect on myogenic differentiation has been rarely studied. We investigated the myotube formation on graphene-based nanomaterials, particularly graphene oxide (GO) and reduced graphene oxide (rGO). GO sheets were immobilized on amine-modified glass to prepare GO-modified glass, which was further reduced by hydrazine treatment for the synthesis of rGO-modified substrate. We studied the behavior, including adhesion, proliferation, and differentiation, of mouse myoblast C2C12 on unmodified, GO-, and rGO-modified glass substrates. According to our analyses of myogenic protein expression, multinucleate myotube formation, and expression of differentiation-specific genes (MyoD, myogenin, Troponin T, and MHC), myogenic differentiation was remarkably enhanced on GO, which resulted from serum protein adsorption and nanotopographical cues. Our results demonstrate the ability of GO to stimulate myogenic differentiation, showing a potential for skeletal tissue engineering applications.

The interactions between cells and materials play critical roles in the success of new scaffolds for tissue engineering, since chemical and physical properties of biomaterials regulate cell adhesion, proliferation, migration, and differentiation. We have developed nanofibrous substrates that possess both topographical cues and electroactivity. The nanofiber scaffolds were fabricated through the electrospinning of polycaprolactone (PCL, a biodegradable polymer) and polyaniline (PANi, a conducting polymer) blends. We investigated the ways in which those properties influenced myoblast behaviors. Neither nanofiber alignment nor PANi concentration influenced cell growth and proliferation, but cell morphology changed significantly from multipolar to bipolar with the anisotropy of nanofibers. According to our analyses of myosin heavy chain expression, multinucleate myotube formation, and the expression of differentiation-specific genes (myogenin, troponin T, MHC), the differentiation of myoblasts on PCL/PANi nanofibers was strongly dependent on both nanofiber alignment and PANi concentration. Our results suggest that topographical cues and the electroactivity of nanofibers synergistically stimulate muscle cell differentiation to make PCL/PANi nanofibers a suitable scaffold material for skeletal tissue engineering.