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      Nanotechnology-Based Gene-Eluting Stents

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          Abstract

          Cardiovascular disease is one of the major causes of death in the world. Coronary stenting in percutaneous coronary intervention (PCI) has revolutionized the field of cardiology. Coronary stenting is seen as a less invasive procedure compared to coronary artery bypass graft (CABG) surgery. Two main types of stents currently exist in the market: bare-metal stents (BMS) and drug-eluting stents (DES). DES were developed in response to problems associated with BMS use, like neointimal hyperplasia leading to restenosis. However, the use of DES engendered other problems as well, like late stent thrombosis (ST), which is a serious and lethal complication. Gene-eluting stents (GES) have recently been proposed as a novel method of circumventing problems seen in BMS and DES. Utilizing nanotechnology, sustained and localized delivery of genes can mitigate problems of restenosis and late ST by accelerating the regenerative capacity of re-endothelialization. Therefore this review seeks to explore the realm of GES as a novel alternative to BMS and DES, and its potential implications in the field of nanotechnology and regenerative medicine.

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          From 3D cell culture to organs-on-chips.

          Dongeun Huh, Geraldine A. Hamilton, Donald E. Ingber (2011)
          3D cell-culture models have recently garnered great attention because they often promote levels of cell differentiation and tissue organization not possible in conventional 2D culture systems. We review new advances in 3D culture that leverage microfabrication technologies from the microchip industry and microfluidics approaches to create cell-culture microenvironments that both support tissue differentiation and recapitulate the tissue-tissue interfaces, spatiotemporal chemical gradients, and mechanical microenvironments of living organs. These 'organs-on-chips' permit the study of human physiology in an organ-specific context, enable development of novel in vitro disease models, and could potentially serve as replacements for animals used in drug development and toxin testing. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Stem-cell-based, tissue engineered tracheal replacement in a child: a 2-year follow-up study.

            Paolo Coppi, Derek J. Roebuck, Clare McLaren … (2012)
            Stem-cell-based, tissue engineered transplants might offer new therapeutic options for patients, including children, with failing organs. The reported replacement of an adult airway using stem cells on a biological scaffold with good results at 6 months supports this view. We describe the case of a child who received a stem-cell-based tracheal replacement and report findings after 2 years of follow-up. A 12-year-old boy was born with long-segment congenital tracheal stenosis and pulmonary sling. His airway had been maintained by metal stents, but, after failure, a cadaveric donor tracheal scaffold was decellularised. After a short course of granulocyte colony stimulating factor, bone marrow mesenchymal stem cells were retrieved preoperatively and seeded onto the scaffold, with patches of autologous epithelium. Topical human recombinant erythropoietin was applied to encourage angiogenesis, and transforming growth factor β to support chondrogenesis. Intravenous human recombinant erythropoietin was continued postoperatively. Outcomes were survival, morbidity, endoscopic appearance, cytology and proteomics of brushings, and peripheral blood counts. The graft revascularised within 1 week after surgery. A strong neutrophil response was noted locally for the first 8 weeks after surgery, which generated luminal DNA neutrophil extracellular traps. Cytological evidence of restoration of the epithelium was not evident until 1 year. The graft did not have biomechanical strength focally until 18 months, but the patient has not needed any medical intervention since then. 18 months after surgery, he had a normal chest CT scan and ventilation-perfusion scan and had grown 11 cm in height since the operation. At 2 years follow-up, he had a functional airway and had returned to school. Follow-up of the first paediatric, stem-cell-based, tissue-engineered transplant shows potential for this technology but also highlights the need for further research. Great Ormond Street Hospital NHS Trust, The Royal Free Hampstead NHS Trust, University College Hospital NHS Foundation Trust, and Region of Tuscany. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              Metalloproteinase inhibitors: biological actions and therapeutic opportunities.

              Gillian Murphy, Jodi Edwards, Andrew Baker (2002)
              Tissue inhibitors of metalloproteinases (TIMPs) are the major cellular inhibitors of the matrix metalloproteinase (MMP) sub-family, exhibiting varying efficacy against different members, as well as different tissue expression patterns and modes of regulation. Other proteins have modest inhibitory activity against some of the MMPs, including domains of netrins, the procollagen C-terminal proteinase enhancer (PCPE), the reversion-inducing cysteine-rich protein with Kazal motifs (RECK), and tissue factor pathway inhibitor (TFPI-2), but their physiological significance is not at all clear. Alpha2-macroglobulin, thrombospondin-1 and thrombospondin-2 can bind to some MMPs and act as agents for their removal from the extracellular environment. In contrast, few effective inhibitors of other members of the metzincin family, the astacins or the distintegrin metalloproteinases, ADAMs have been identified. Many of these MMP inhibitors, including the TIMPs, possess other biological activities which may not be related to their inhibitory capacities. These need to be thoroughly characterized in order to allow informed development of MMP inhibitors as potential therapeutic agents. Over activity of MMPs has been implicated in many diseases, including those of the cardiovascular system, arthritis and cancer. The development of synthetic small molecule inhibitors has been actively pursued for some time, but the concept of the use of the natural inhibitors, such as the TIMPs, in gene based therapies is being assessed in animal models and should provide useful insights into the cell biology of degradative diseases.
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                Author and article information

                Journal
                Title: Molecular Pharmaceutics
                Abbreviated Title: Mol. Pharmaceutics
                Publisher: American Chemical Society (ACS)
                ISSN (Print): 1543-8384
                ISSN (Electronic): 1543-8392
                Publication date Created: April 01 2013
                Publication date (Electronic): February 26 2013
                Publication date (Print): April 01 2013
                Volume: 10
                Issue: 4
                Pages: 1279-1298
                Affiliations
                [1 ]Centre for Nanotechnology & Regenerative Medicine, UCL Division of Surgery & Interventional Science, University College London, London NW3 2QG, United Kingdom
                [2 ]UCL Medical School, University College London, London WC1E 6BT, United Kingdom
                [3 ]Biomaterials & Advanced Drug Delivery Laboratory, School of Medicine, Stanford University, California 94305, United States
                [4 ]Pharmidex Pharmaceutical Services Ltd., London W1S 1YH, United Kingdom
                [5 ]Royal Free London NHS Foundation Trust, London NW3 2QG, United Kingdom
                Article
                DOI: 10.1021/mp3006616
                PubMed ID: 23394068
                SO-VID: 8b5cb597-1205-40b5-9413-ec698c0f5e57
                Copyright © © 2013
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