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Patient-specific cancer therapies can evolve by vitalizing the mother tissue-like cancer niche, cellular profile, genetic signature, and drug responsiveness. This evolution has enabled the elucidation of a key mechanism along with development of the mechanism-driven therapy. After surgical treatment, glioblastoma (GBM) patients require prompt therapy within 14 days in a patient-specific manner. Hence, this study approaches direct culture of GBM patient tissue (1 mm diameter) in a microchannel network chip. Cancer vasculature-mimetic perfusion can support the preservation of the mother tissue-like characteristic signatures and microenvironment. When temozolomide and radiation are administered within 1 day, the responsiveness of the tissue in the chip reflected the clinical outcomes, thereby overcoming the time-consuming process of cell and organoid culture. When the tissue chip culture is continued, the intact GBM signature gets lost, and the outward migration of stem cells from the tissue origin increases, indicating a leaving-home effect on the family dismantle. Nanovesicle production using GBM stem cells enables self-chasing of the cells that escape the temozolomide effect owing to quiescence. The anti-PTPRZ1 peptide display and temozolomide loading to nanovesicles awakes cancer stem cells from the quiescent stage to death. This study suggests a GBM clinic-driven avatar platform and mechanism-learned nanotherapy for translation.

Shape memory materials have been successfully applied to minimally invasive implantation of medical devices. However, organ-movement-specific shape programing at a microscale level has never been demonstrated despite significant unmet needs. As vein-to-artery grafting induces vein dilation and stenosis, a polymeric self-enclosable external support (SES) is designed to wrap the vascular out-wall. Its micropores are programmed to increase sizes and interconnections upon dilation. Vessel dilation promotes venous maturation, but overdilation induces stenosis by disturbed blood flow. Therefore, the unique elastic shape-fixity of SES provides a foundation to enable a stable microscale shape transition by maintaining the vein dilation. The shape transition of micropore architecture upon dilation induces beneficial inflammation, thereby regenerating vasa vasorum and directing smooth muscle cell migration toward adventitia with the consequent muscle reinforcement of veins. This game-changer approach prevents the stenosis of vein-to-artery grafting by rescuing ischemic disorders and promoting arterial properties of veins.

Remarkable achievements have been made in the clinical application of mechanical circulatory support and cardiac transplantation for patients with end-stage heart failure. Despite the successes, complications associated with these therapies continue to drive cardiac regenerative research utilizing stem cell based therapies. Multiple stem cell lineages hold clinical promise for cardiac regeneration—mostly through cellular differentiation, cellular fusion, and paracrine signaling mechanisms. Bone marrow-derived endothelial progenitor cells are among the most intriguing and controversial cell types currently being investigated. Formidable barriers exist, however, in finding the ideal cardiac regenerative stem cell, such as identifying specific lineage markers, optimizing in vitro cellular expansion and improving methods of stem cell delivery. Hybrid approaches of cardiac regeneration using stem cell therapies in conjunction with immunomodulation after cardiac transplantation or with mechanical circulatory support produce cutting edge stem cell technologies. This review summarizes the current knowledge and therapeutic applications of stem cells in patients with end-stage heart failure, including stem cell therapy after implantation of mechanical circulatory support and cardiac transplantation. J. Cell. Biochem. 115: 1217–1224, 2014. © 2014 Wiley Periodicals, Inc.

Inserting a graft into vessels with different diameters frequently causes severe damage to the host vessels. Poor flow patency is an unresolved issue in grafts, particularly those with diameters less than 6 mm, because of vessel occlusion caused by disturbed blood flow following fast clotting. Herein, successful patency in the deployment of an ≈2 mm diameter graft into a porcine vessel is reported. A new library of property-tunable shape-memory polymers that prevent vessel damage by expanding the graft diameter circumferentially upon implantation is presented. The polymers undergo seven consecutive cycles of strain energy-preserved shape programming. Moreover, the new graft tube, which features a diffuser shape, minimizes disturbed flow formation and prevents thrombosis because its surface is coated with nitric-oxide-releasing peptides. Improved patency in a porcine vessel for 18 d is demonstrated while occlusive vascular remodeling occurs. These insights will help advance vascular graft design.

Recently, significant progress has been made in developing “stimuli-sensitive” biomaterials as a new therapeutic approach to interact with dynamic physiological conditions. Reactive oxygen species (ROS) production has been implicated in important pathophysiological events, such as atherosclerosis, aging, and cancer. ROS are often overproduced locally in diseased cells and tissues, and they individually and synchronously contribute to many of the abnormalities associated with local pathogenesis. Therefore, the advantages of developing ROS-responsive materials extend beyond site-specific targeting of therapeutic delivery, and potentially include navigating, sensing, and repairing the cellular damages via programmed changes in material properties. Here we review the mechanism and development of biomaterials with ROS-induced solubility switch or degradation, as well as their performance and potential for future biomedical applications.

An estimated 16 million people in the United States have coronary artery disease (CAD), and approximately 325,000 people die annually from cardiac arrest. About two-thirds of unexpected cardiac deaths occur without prior recognition of cardiac disease. A vast majority of these deaths are attributable to the rupture of 'vulnerable atherosclerotic plaques'. Clinically, plaque vulnerability is typically assessed through imaging techniques, and ruptured plaques leading to acute myocardial infarction are treated through angioplasty or stenting. Despite significant advances, it is clear that current imaging methods are insufficiently capable for elucidating plaque composition--which is a key determinant of vulnerability. Further, the exciting improvement in the treatment of CAD afforded by stenting procedures has been buffered by significant undesirable host-implant effects, including restenosis and late thrombosis. Nanotechnology has led to some potential solutions to these problems by yielding constructs that interface with plaque cellular components at an unprecedented size scale. By leveraging the innate ability of macrophages to phagocytose nanoparticles, contrast agents can now be targeted to plaque inflammatory activity. Improvements in nano-patterning procedures have now led to increased ability to regenerate tissue isotropy directly on stents, enabling gradual regeneration of normal, physiologic vascular structures. Advancements in immunoassay technologies promise lower costs for biomarker measurements, and in the near future, may enable the addition of routine blood testing to the clinician's toolbox--decreasing the costs of atherosclerosis-related medical care. These are merely three examples among many stories of how nanotechnology continues to promise advances in the diagnosis and treatment of vulnerable atherosclerotic plaques.

Stem cells are a promising cell source for regenerative medicine due to their differentiation and self-renewal capacities. In the field of regenerative medicine and tissue engineering, a variety of biomedical technologies have been tested to improve proangiogenic activities of stem cells. However, their therapeutic effect is found to be limited in the clinic because of cell loss, senescence, and insufficient therapeutic activities. To address this type of issue, advanced techniques for biomaterial synthesis and fabrication have been approached to mimic proangiogenic microenvironment and to direct proangiogenic activities. This review highlights the types of polymers and design strategies that have been studied to promote proangiogenic activities of stem cells. In particular, scaffolds, hydrogels, and surface topographies, as well as insight into their underlying mechanisms to improve proangiogenic activities are the focuses. The strategy to promote angiogenic activities of hMSCs by controlling substrate repellency is introduced, and the future direction is proposed.

Pretreatment of tissue by using antibiotics is a critical step to prevent microbial contamination before venous transplantation. In this study, the optimal time and temperature of antibiotic solution treatment for maintaining cellular viability with antibacterial effect were investigated. The antibiotic-nutrient solutions were composed of cefoxitin, lincomycin, vancomycin, and polymyxin B in RPMI-1640 medium. After various antibiotic solution treatment times (4, 8, and 12 h) and temperatures (4, 25, and 37 degrees C), the viabilities of cells dissociated from veins (jugular vein, femoral vein, superior vena cava, and inferior vena cava) were determined. Double staining by Griffonia simplicifolia agglutins-fluorescein isothiocyanate (GS1-FITC) and propidium iodide was used. To measure the antibacterial effect of the antibiotic solution, canine veins were artificially infected by 3 kinds of bacteria (Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae) and were treated by antibiotic solutions as viability test conditions. After the treatment with the antibiotic solution, the tissue was minced, and the homogenized tissue fraction was cultured on standard method agar. The colony that seemed to be resistant to the antibiotic solution was counted. At 37 and 25 degrees C, the viability of whole cells decreased significantly Asymptotic Significance 2-tailed (Asymp.Sig 2-tailed) < 0.05 after 4 h of antibiotic solution treatment, whereas at 4 degrees C it began to reduce significantly after 8 h of treatment. By antibiotic solution treatment at all 3 temperatures for 4 h, no significant difference in viability of the endothelial cells and whole cells was observed. To maintain the donor vein's cellular viability until transplantation, antibiotic solution treatment for 4 h at 4 degrees C is assumed to be appropriate.