Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.

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Principles of nanoparticle design for overcoming biological barriers to drug delivery

The intrinsic limits of conventional cancer therapies prompted the development and application of various nanotechnologies for more effective and safer cancer treatment, herein referred to as cancer nanomedicine. Considerable technological success has been achieved in this field, but the main obstacles to nanomedicine becoming a new paradigm in cancer therapy stem from the complexities and heterogeneity of tumour biology, an incomplete understanding of nano-bio interactions and the challenges regarding chemistry, manufacturing and controls required for clinical translation and commercialization. This Review highlights the progress, challenges and opportunities in cancer nanomedicine and discusses novel engineering approaches that capitalize on our growing understanding of tumour biology and nano-bio interactions to develop more effective nanotherapeutics for cancer patients.

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Cancer nanomedicine: progress, challenges and opportunities.

This Perspective explores and explains the fundamental dogma of nanoparticle delivery to tumours and answers two central questions: ‘how many nanoparticles accumulate in a tumour?’ and ‘how does this number affect the clinical translation of nanomedicines?’

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Analysis of nanoparticle delivery to tumours

Engineered nanoparticles have the potential to revolutionize the diagnosis and treatment of many diseases; for example, by allowing the targeted delivery of a drug to particular subsets of cells. However, so far, such nanoparticles have not proved capable of surmounting all of the biological barriers required to achieve this goal. Nevertheless, advances in nanoparticle engineering, as well as advances in understanding the importance of nanoparticle characteristics such as size, shape and surface properties for biological interactions, are creating new opportunities for the development of nanoparticles for therapeutic applications. This Review focuses on recent progress important for the rational design of such nanoparticles and discusses the challenges to realizing the potential of nanoparticles.

Strategies in the design of nanoparticles for therapeutic applications

With digital equipment becoming increasingly networked, either on wired or wireless networks, for personal and professional use alike, distributed software systems have become a crucial element in information and communications technologies. The study of these systems forms the core of the ARLES' work, which is specifically concerned with defining new system software architectures, based on the use of emerging networking technologies. In this context, we concentrate on the study of distributed systems which bring to life the vision of ubiquitous computing systems, also known as ambient intelligence.

반도체 공정 overview

Background Context: Mesenchymal stem cells (MSC) are being used for spine and orthopaedic surgical and research applications. Bone marrow and fat are the most commonly used sources of these cells. Purpose: To describe a new technique allowing the isolation and expansion of human MSC from cortical bone. Study Design: MSC from human cortical bone (vertebral lamina) were isolated, expanded, and verified in vitro. Methods: Human MSC were isolated from laminar bone obtained during surgery (decompression/laminectomy). They were then cultured and assessed using fluorescence-activated cell sorting techniques for MSC markers, colonyforming unit assays, and multilineage differentiation. Results: Isolated and cultured cells demonstrated MSC markers and trilineage differentiation confirming their stemness. International Journal of Translational Science, Vol. 2016, 71–86. doi: 10.13052/ijts2246-8765.2016.005 c © 2016 River Publishers. All rights reserved. 72 J. S. Fernandez-Moure et al. Conclusion: A novel method for the isolation of MSC from cortical bone has been described. These cells have significant current and future application in spine and orthopaedic surgery; and both the source of the cells and particular characteristics of the cortical bone derived MSC have advantages over currently used MSC obtained from other sources.

https://riverpublishers.com/journal/journal_articles/RP_Journal_2246-8765_20161005.pdf

Characterization of Mesenchymal Stem Cells from Human Cortical Bone

[This corrects the article on p. 54 in vol. 5, PMID: 28983481.].

Corrigendum: Heparan Sulfate: A Potential Candidate for the Development of Biomimetic Immunomodulatory Membranes.

Disclosed are trilaminate collagen-based tissue scaffolds that exhibit remarkable morphological mimicry to that of the natural mammalian periosteum tissue they are useful in remodeling. In particular embodiments, periosteum-modeling trizonal membranes for reforming and regrowing human bone tissue are provided that are composed of a first zone of compact collagen, a second layer of collagen-elastin, and a third layer of biomineralized collagen.

Trizonal membranes for periosteum regeneration

Not all stem cells are created equal: a comparative analysis of osteogenic potential in compact bone and adipose-derived mesenchymal stem cells

The present invention relates to a polymer scaffold design and method for treating segmental long bone defects without amputation that permits permanent regrowth of bone in the area of the segmental defect, without external fixation or other problems inherent in current systems. The polymer scaffold is preferably made from a poly(ester urea) polymer and includes an outer shell, sized to fit over a segmental defect in a bone, and a collagen containing material. In some embodiments, the collagen containing material is placed in a polymer insert sized to fit within the segmental bone defect and within said outer shell. In some embodiments, the outer shell may contain struts running longitudinal struts along the inside surface of the outer shell. In some of these embodiments, the insert will have a corresponding set of grooves sized to receive the struts.

Ennio Tasciotti

Papers

Characterization of Mesenchymal Stem Cells from Human Cortical Bone

Corrigendum: Heparan Sulfate: A Potential Candidate for the Development of Biomimetic Immunomodulatory Membranes.

Trizonal membranes for periosteum regeneration

Not all stem cells are created equal: a comparative analysis of osteogenic potential in compact bone and adipose-derived mesenchymal stem cells

Modular device for preventing compression and instability in a segmental defect repair scaffold