We introduce a theoretical model based upon the kinetic Monte Carlo (KMC) simulation approach capable of quantifying chain shuttling copolymerization (CSP) of ethylene and 1-octene in a semibatch operation. To make a deeper understanding of kinetics and evolution of microstructure, the reversible transfer reaction is first investigated by applying each of the individual catalysts to the reaction media, and the competences and shortcomings of a qualified set of CSP catalysts are discussed based on coordinative chain transfer copolymerization (CCTP) requirements. A detailed simulation study is also provided, which reflects and compares the contributions of chain transfer reversibility and other chain breaking reactions in controlling distribution fashion of molecular weight and chemical composition. The developed computer code is executed to capture developments in dead chain concentration and time-driven composition drift during CCTP. Also, the effect of chain shuttling agent (CSA) on the copolymerization kinetics is theoretically studied by simultaneous activation of both catalysts. In this way, it is attempted to make control over comonomer incorporation in the course of copolymerization. The molecular-level criteria reflecting copolymer properties, i.e., ethylene sequence length distribution and longest ethylene sequence length, as the signature of CSA performance, are virtually simulated in the presence and absence of hydrogen to capture an image on gradient copolymers in CCTP and blocks with gradually changing composition in CSP.

Background: There is significant interest in using nanofibers in tissue engineering from stem cells. The transdifferentiation of mesenchymal stem cells into the hepatic lineage in a nanofibrous structure has not been reported. In this study, a three dimensional nanofibrous scaffold is introduced for differentiation of human bone marrow derived mesenchymal stem cells (hBMSCs) into hepatocytes. Methods: A scaffold composed of Poly (e-caprolactone), collagen and polyethersulfone was fabricated by the electrospinning technique. After characterization of isolated hBMSCs, the performance of the cells on the scaffold was evaluated by Scanning Electron Microscopy (SEM) and MTT assay. Cytological, molecular and biochemical markers were measured to confirm differentiation potential of hBMSCs into hepatocytes. Results: The isolated cells possessed the basic properties of mesenchymal stem cells (MSCs). Based on scanning electron microscope (SEM) analysis and MTT assay, it was shown that the cells adhere, penetrate and proliferate on the nanofibers. Cultured cells on the nanofibers differentiated into hepatocyte-like cells and expressed hepatocyte specific markers such as albumin, a-fetoprotein, cytokeratin-18, cytokeratin-19 and cytochrome P450 3A4 at mRNA levels. Appearance of a considerable number of albumin-positive cells cultivated on the scaffold (47 Ϯ 4%) as compared to the two-dimensional culture system (28 Ϯ 6%) indicates the supporting role of the scaffold. The efficiency of the cells to produce albumin, urea, transferrin, serum glutamic pyruvic transaminase and serum oxaloacetate aminotransferase in hepatocytes on the scaffold further attest to the functionality of the cells. Conclusion:The data presented in this study show that the engineered nanofibrous scaffold is a conductive matrix which supports and enhances MSC development into functional hepatocyte-like cells.

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Tissue engineering of implantable cellular constructs is an emerging cellular therapy for hepatic disease. In this study, we tested the ability of poly(ε-caprolactone) (PCL) nanofiber scaffold to support and maintain hepatic differentiation of human cord blood-derived unrestricted somatic stem cells (USSCs) in vitro. USSCs, self-renewing pluripotent cells, were isolated from human cord blood. The electrospun PCL nanofiber porous scaffold was constructed of uniform, randomly oriented nanofibers. USSCs were seeded onto PCL nanofiber scaffolds, and were induced to differentiate into hepatogenic lineages by culturing with differentiation factors for 6 weeks. RT-PCR analysis of endoderm and hepatic-specific gene expression, immunohistochemical detection of cytokeratin 18 (CK-18), α-fetoprotein, albumin, glycogen storage and indocyanine green uptake confirmed the differentiation of USSCs into endoderm and hepatocyte-like cells. In the present study, we show that hepatocyte-like cells differentiated from USSCs on the PCL nanofiber scaffold can be candidate for tissue engineering and cell therapy of hepatic tissues.

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