Electrospinning has developed as a unique and versatile process to fabricate ultrathin fibers in the form of nonwoven meshes or as oriented arrays from a variety of polymers. The very small dimension of these fibers can generate a high surface area, which makes them potential candidates for various biomedical and industrial applications. The objective of the present study was to develop nanofibers from polyphosphazenes, a class of inorganic-organic polymers known for high biocompatibility, high-temperature stability, and low-temperature flexibility. Specifically, we evaluated the feasibility of developing bead-free nonwoven nanofiber mesh from poly[bis(p-methylphenoxy)phosphazene] (PNmPh) by electrospinning. The effect of process parameters such as nature of solvent, concentration of the polymer solution, effect of needle diameter, and applied potential on the diameter and morphology (beaded or bead-free) of resulting nanofibers were investigated. It was found that solution of PNmPh in chloroform at a concentration range of 7% (wt/v) to 9% (wt/v) can be readily electrospun to form bead-free fibers at room temperature. The mean diameter of the fibers obtained under optimized spinning condition was found to be approximately 1.2 microm. The bead-free, cylindrical nanofibers formed under the optimized condition showed a slightly irregular surface topography with indentations of a few nanometer scale. Further, the electrospun nanofiber mats supported the adhesion of bovine coronary artery endothelial cells (BCAEC) as well as promoted the adhesion and proliferation of osteoblast like MC3T3-E1 cells.

Amino acid ester substituted polyphosphazenes are attractive candidates for various biomedical applications because of their biocompatibility, controllable hydrolytic degradation rates, and nontoxic degradation products. In this study, the biocompatibility of three L-alanine ethyl ester functionalized polyphosphazenes was evaluated in a subcutaneous rat model. The polymers used in the study were poly[bis(ethylalanato)phosphazene] (PNEA), poly[(50% ethylalanato) (50% methylphenoxy) phosphazene] (PNEA(50)mPh(50)), and poly[(50% ethylalanato)(50% phenyl phenoxy) phosphazene] (PNEA(50)PhPh(50)). Polymer disks of diameter 7.5 mm were prepared by a solvent evaporation technique and were implanted subcutaneously in rats. After 2, 4, and 12 weeks, the polymer along with the surrounding tissues were excised, prepared, and viewed by light microscopy to evaluate the tissue responses of the implanted polymers. The tissue responses were classified as minimal, mild, or moderate, based on a biocompatibility scheme developed in our laboratory. Minimal inflammation was characterized by the presence of few neutrophils, erythrocytes, and lymphocytes; mild response was characterized by the predominant presence of macrophages, fibroblasts, or giant cells; and moderate inflammation was characterized by the abundance of macrophages, giant cells, and by the presence of tissue exudates. The in vivo degradation profiles of the polymers at various time points were evaluated by gel permeation chromatography (GPC). PNEA and PNEA(50)mPh(50) matrices elicited varying levels of tissue responses during the 12-week implantation period. At 2 weeks both polymers evoked a moderate response, and by 12 weeks the response was found to be mild. However, PNEA(50)PhPh(50) elicited a mild response at the end of 2 weeks and demonstrated a further decreased inflammatory response after 12 weeks. The in vivo degradation of the polymers was followed by determining the molecular weights of the explanted polymer disks. PNEA and PNEA(50)mPh(50) disks showed significant decrease in molecular weight after 2 weeks of implantation. The molecular weights of PNEA and PNEA(50)mPh(50) residues could not be determined by GPC after 12 weeks of implantation because of almost complete degradation. On the other hand the in vivo degradation of PNEA(50)PhPh(50) was found to be slow, with a 63% loss in molecular weight in 12 weeks. Furthermore, this polymer maintained its shape and structure during the entire study. Thus, these polymers demonstrated excellent tissue compatibility and in vivo biodegradability and can be potential candidates for various biomedical applications.

The versatility of polymers for tissue regeneration lies in the feasibility to modulate the physical and biological properties by varying the side groups grafted to the polymers. Biodegradable polyphosphazenes are high molecular weight polymers with alternating nitrogen and phosphorus atoms in the backbone. This study is the first of its kind to systematically investigate the effect of side group structure on the compressive strength of novel biodegradable polyphosphazene based polymers as potential materials for tissue regeneration. The alanine polyphosphazene based polymers, poly [bis(ethyl alanato) Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Moreover cells on the surface of the polymers expressed type I collagen, alkaline phosphatase, osteocalcin, osteopontin, and bone sialoprotein which are characteristic genes for osteoblast maturation, differentiation, and mineralization. NIH Public Access

Poor prognoses remain the most challenging aspect of hepatocellular carcinoma (HCC) therapy. Consequently, alternative therapeutics are essential to control HCC. This study investigated the anticancer effects of safranal against HCC using in vitro, in silico, and network analyses. Cell cycle and immunoblot analyses of key regulators of cell cycle, DNA damage repair and apoptosis demonstrated unique safranal-mediated cell cycle arrest at G2/M phase at 6 and 12 h, and at S-phase at 24 h, and a pronounced effect on DNA damage machinery. Safranal also showed pro-apoptotic effect through activation of both intrinsic and extrinsic initiator caspases; indicating ER stress-mediated apoptosis. Gene set enrichment analysis provided consistent findings where UPR is among the top terms of up-regulated genes in response to safranal treatment. Thus, proteins involved in ER stress were regulated through safranal treatment to induce UPR in HepG2 cells.