These findings aid in the systematic understanding of the effects of in vitro parameters on engineered vessels and will be useful for the translation of vessel culture techniques to human cells for the development of autologous human vascular grafts.

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Gelatin is a natural polymer used in pharmaceutical and medical applications, especially in the production of biocompatible and biodegradable wound dressings and drug delivery systems. Gelatin granules hydrate, swell and solubilize in water, and rapidly degrade in vivo. The durability of these materials could, however, be prolonged by cross-linking by aldehydes, carbodiimides, and aldose sugars, but the biocompatibility of collagenous biomaterials is profoundly influenced by the nature and extent of cross-linking. In this study, gelatin sponges were prepared by using various cross-linkers such as glutaraldehyde (GA), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDAC), and D-fructose. The effects of the type and the amount of cross-linker on thermal and mechanical properties, stability, and cytotoxicity were investigated. The mechanical analysis data showed that an increase in the amount of GA in the sponge structures caused a slight increase in the modulus of elasticity but had almost no effect on the tensile strength. Increase in the EDAC concentration produced a maximum in the modulus of elasticity and tensile strength values. The stability of the sponges and the time required for complete degradation in aqueous media increased in parallel with the cross-linker content. In vitro studies carried out with fibroblast cells demonstrated a higher cell viability for the samples cross-linked with low concentrations of GA than for those cross-linked with EDAC.

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancers with a median survival of 6 months after diagnosis. Intrinsic resistance to chemotherapeutics and lack of effective targeted therapies are the major factors contributing to dismal prognosis. Several important genetic alterations (i.e., mutations, deletions) have been identified to be involved in the initiation and progression of pancreatic cancer, including KRAS and inactivation of tumor suppressors, such as TP53, SMAD4 and CDKN2A. Unique tumor microenvironment with excessive stroma due to desmoplastic reaction is one of the major characteristics of PDAC, promoting tumor growth and leading to treatment failures. In addition, tumor stroma represents an important biological barrier for drug delivery and successful treatment of PDAC. Small interfering RNA (siRNA) has recently emerged as a potential and targeted therapeutic approach which is now evaluated in clinical trials. However, siRNAbased therapeutics face important challenges, including rapid serum degradation, poor tumor cell uptake and cellular uptake, leading to off-target effects. Therefore, there is a great need for the development of safe and effective nanoparticles for better tumor-specific delivery of anti-cancer therapeutics. In this article, the main challenges in the treatment of pancreatic cancer and recent advancements on nano delivery systems of chemotherapeutics and gene-targeted agents, used both in preclinical and clinical trials are reviewed.

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