Chitosan—A versatile semi-synthetic polymer in biomedical applications

Recent progress in the structural modification of chitosan for applications in diversified biomedical fields

Chitosan, a linear and semicrystalline polysaccharide composed of randomly distributed β, 1–4 linkages of N-acetyl-d-glucosamine and d-glucosamine, obtained from partial deacetylation of chitin, is a natural polysaccharide present in shells of marine crustaceans and cell walls of fungi, as well as other invertebrate organisms. This biopolymer is a polyelectrolyte with reactive functional groups, high adsorption capacity, mucoadhesive, biodegradable, bioresorbable, innately biocompatible and non-toxic to living tissues as well as having antibacterial, antifungal, and antitumor activity. These features highlight the suitability and extensive applications of chitosan in the biomedical field, such as implant coatings, wound healing devices, tissue engineering, and drug delivery systems. However, its limited solubility in water and other organic solvents, poor colloidal stability, poor mechanical strength, and high swelling ratio limits its full exploitation for some biomedical purposes. To overcome these limitations, chitosan-inorganic composites have been formulated to enable the adjustment of the desired properties for intended applications. This chapter focused on the fundamentals of chitosan and its composites and how the chitosan-inorganic materials, called “green composites” or “bionanocomposites,” can be utilized in biomedical applications.

To the Editor: The article by Xue et al1 on human embryonic stem cell-derived pacemakers illustrates that embryonic stem cells differentiated into spontaneously beating cardiocytes may function as biological pacemakers and mentions a potential limitation: The intrinsic pacemaker rate was slower than desirable. They suggest that incorporating HCN pacemaker channel genes might achieve more desirable rates, an idea consistent with our published results using HCN2 in gene- and adult human mesenchymal stem cell (hMSC)-based therapies.2–4 However, certain of the comments by Xue et al misinterpret our own work on HCN-loaded hMSCs. They state that “…these modified, undifferentiated, human mesenchymal stem cells are incapable of pacing quiescent cells because the former are neither electrically active nor genuine cardiac cells” (p 19). This statement suggests a misunderstanding of the rationale and underlying biophysics of the hMSC experiments. In fact, generation of pacemaker activity does not require delivery of an “excitable differentiated cardiac cell,” but only that the delivered cell (1) carry sufficient pacemaker current and (2) make gap junctions; thus, the hMSC-myocyte pair should behave as a pacemaker unit entirely equivalent to a single heart cell with substantial if. We clearly demonstrated both …

What's in a Name?

A safe and efficient drug carrier must offer protection to human tissues in which it is admin‐ istered as well as protection to the drugs against degradation, improve therapeutic effect, prolong biological activity, control drug release rate, and decrease the frequency of adminis‐ tration. These characteristics could be achieved by using chitosan to prepare carriers of drugs. It is almost the only cationic polysaccharide in nature with a great innate medical potential. Chitosan, a cationic polymer of natural origin, is a remarkable example of an excipient which currently has enormous potential for using in pharmaceutical dosage forms because of its properties as polyelectrolyte with reactive functional groups, gel-forming capability, high adsorption capacity, biodegradability and biocompatible and non-toxic to living tissues as well as having antibacterial, antifungal and antitumor activity. These functional properties provide suitability and extensive pharmaceutical applications such as for the preparation of drug delivery systems (drug conjugate, micro/nanoparticles, hydrogels, emulsions, biodegradable release system, etc.) and for regenerative medicine for many components such as proteins/ peptides, growth factors, anti-inflammatory drugs, antibiotics intended to be administered in non parenteral routes (oral, topical, intranasal, vaginal, rectal and ocular). Interesting appli‐ cations of chitosan has been receiving considerable attention since it has been developed systems more versatile by the incorporation of chitosan and other components in novel systems. They have provided a strategy for the functionalization by modulating physico‐

It is the kind of thing you see everyday. In the elaborate poetics of graffiti: the signatures left so artfully, the politics of slashing through them, crossing them out, erasing them, replicating them all over town.... Something in its roughened surface points to a residue in things, a something that refuses to disappear, . . . gathering a counter-force to a point of intensity that both slashes at itself and spits at the world.

5 ISSN 1746-0751 10.2217/RME.09.84 © 2010 Future Medicine Ltd Regen. Med. (2010) 5(1), 5–6 “To further the advancement of responsible stem cell research, the Canadian Stem Cell Foundation ... released the Stem Cell Charter in September 2009 ... The promulgation and promotion of this Charter aims to prospectively frame stem cell research and to serve as a benchmark for the guidance of international and national initiatives in both scientific research and policymaking.” Bartha Maria Knoppers Author for correspondence: Director, Centre of Genomics & Policy, Faculty of Medicine, Department of Human Genetics, McGill University, 740 Dr. Penfield Avenue, Suite 5214, Montreal, Quebec, H3A 1A4 Canada Tel.: +1 514 398 8866; Fax: +1 514 398 8954; bartha.knoppers@mcgill.ca

How physicians and scientists can respond responsibly and effectively to religiously based opposition to human embryonic stem cell research

I: Perspectives For Tissue Engineering And Stem Cells. 1. Tissue engineering: confronting the transplantation crisis R. Nerem. 2. Human embryonic stem cells- realising the potential J. McWhir, A. Thomson, V. Sottile. 3. Human embryonic or adult stem cells: an overview on ethics and perspectives for tissue engineering P. Henon. 4. Stem cell biology and plasticity E. Kansu. II: Stem Cells In Tissue Engineering And Cell-Based Therapies. 5. Liver tissue engineering: successes and limitations V. Dixit, Y.M. Elcin. 6. Pancreatic islet and stem cell transplantation in diabetes mellitus: results and perspectives R.G. Bretzel. 7. Cell based therapy of chronic degenerative diseases of the central nervous system Ye.V. Pankratov, A.I. Ivanov, T.D. Kolokoltsova, Ye.A. Nechayeva, I.F. Radayeva, L.I. Korochkin, A.V. Revischin, S.A. Naumov, I.A. Khlusovi, A.I. Autenshlus. 8. CD 34+ cells in hematopoietic stem cell transplantation T. Demirer. 9. The effects of different growth factors on human bone marrow stromal cells differentiating into hepatocyte-like cells Y.-S. Weng, H.-Y. Lin, Y.-J. Hsiang, C.-T. Hsieh, W.-T. Li. III: Biomarkers For Tissue-Engineered Products. 10. Oxidative DNA damage biomarkers used in tissue-engineered skin H. Rodriguez, P. Jaruga, M. Birincioglu, P.E. Barker, C. O'Connell, M. Dizdaroglu. 11. Biomarkers used to detect genetic damage in tissue-engineered skin C. O'Connell, P.E. Barker, M. Marino, P. McAndrew, D.H. Atha, P. Jaruga, M. Birincioglu, M. Dizdaroglu, H. Rodriguez. IV: Biomaterials In TissueEngineering And Repair. 12. Design peptide scaffolds for regenerative medicine S. Zhang, C.E. Semino. 13. Progresses in synthetic vascular prostheses: toward the endothelialization M. Crombez, D. Mantovani. 14. Adhesion and growth of rat aortic smooth muscle cells on lactide-based polymers L. Bacakova, M. Lapcikova, D. Kubies, F. Rypacek. 15. Biodegradable copolymers carrying cell-adhesion peptide sequences V. Proks, L. Machova, S. Popelka, F. Rypacek. 16. Polymer based scaffolds and carriers for bioactive agents from different natural origin materials P.B. Malafaya, M.E. Gomes, A.J. Salgado, R.L. Reis. 17. Preparation and characterization of natural/synthetic hybrid scaffolds G. Khang, S.J. Lee, C.W. Han, J.M. Rhee, H.B. Lee. 18. Polyhipe polymer: a novel scaffold for in vitro bone tissue engineering M. Bokhari, M. Birch, G. Akay. 19. Pancreatic islet culture and transplantation using chitosan and PLGA scaffolds Y.M. Elcin, A.E. Elcin, R.G. Bretzel, T. Linn. V: Gene Therapy And Other Approaches. 20. Challenges and prospects for targeted transgenesis in livestock M.M. Marques, A.J. Thomson, J. McWhir. 21. Controlled release of bioactive agents in gene therapy and tissue engineering D.S. Keskin, V. Hasirci. 22. Interleukin 1 (IL-1) induces the activation of stat3 A. Arman, P.E. Auron. 23. The use of antibodies in diagnosis and therapy of cancer A. Muvaffak, Hasirci. 24. Detection of phage displayed peptides with blocking ability in vascular endothelial growth factor (VEGF) model B. Erdag, B.K.

Nanoparticles for transcutaneous vaccinationCould nanotechnology prevent onethird of all deaths caused by infections?Many of these deaths are due to the lack of efficient prophylaxis and treatment options owing to the unavailability of vaccines and antibiotics or due to the development of drug resistances.Thus, it is of upmost importance to develop strategies for preventing and treating infectious diseases.In this mini-review in Microbial Biotechnology, the authors argue that there is no doubt that nanotechnology holds great promise for vaccination and especially transcutaneous immunization.Key issues that will have to be solved in the future are how nano delivery devices can transport a sufficient dose of the vaccine across the SC and how this can be achieved without opening the skin barrier for the invasion of pathogens or harmful material.Currently, ultra-flexible liposomes are the best investigated carriers in this aspect./feh

The analysis of Parliamentary debates provides the opportunity to assess the political context of Canadian legislation, particularly in controversial areas such as stem cell research. Parliamentary debates surrounding the recent Assisted Human Reproduction Act, (1) which lasted nearly a decade, were dominated by religious conservatives. At the forefront of the debate were issues such as the moral status of the embryo and the regulation of somatic cell nuclear transfer (SCNT). The resulting restrictive statutory provisions that ban SCNT ultimately arose from a convergence of rhetoric on dignity and the moral status of the embryo, and the resultant promotion of adult stem cell research. Approach We qualitatively analyzed the Canadian Hansard debates concerning stem cell policy from 1994 to 2004 by assigning codes to full text databases. (2) While the majority of the debates related to ethical issues, we focused on descriptions of scientific research by politicians, references to scientific progress, both proven and speculative, economic arguments, references to media coverage and direct quotes from scientific and other experts because the media and experts are major sources of information for politicians. The Parliamentary Debates Descriptions of Scientific Research We found Canadian politicians lack an understanding of scientific research, resulting in inflammatory statements on both costs and benefits of embryonic human stem cell research. Politicians generally misunderstood the process of obtaining embryonic stem cells and SCNT, a methodology used in both therapeutic and reproductive Both therapeutic and reproductive (human) cloning commence with the use of SCNT. However, reproductive cloning and therapeutic cloning for research purposes are used for different reasons with significantly different endpoints. Politicians generally conflate the two procedures. For instance, building upon the public's distaste for reproductive cloning, one member described the research of the Raelians, a Canadian research group who claim to have successfully cloned a human being, (3) in conjunction with therapeutic The member stated that we took one of [the Speaker's] cells, extracted the nucleus and put it into an ovum, one could stimulate it electrically and allow it to grow. The so-called therapeutic clone would be to take the immature model of Mr. Speaker and extract an organ, if he needed one, killing the clone in the That is so-called somatic nuclear cell transfer or therapeutic cloning. (4) Another member stated, I would suggest that most members of the House do not understand the difference between therapeutic and reproductive Certainly most people in Canada do not totally understand the difference between the two. In reality, there is not any difference. It is the same process. (5) Such statements demonstrate the lack of understanding of scientific research by politicians, and underscore the need for further education of all policy makers on issues relating to stem cell research prior to the creation of ideologically driven legislation. Alternatively, and of greater concern, these statements may also indicate a willingness of politicians to mislead the House and the public on controversial scientific research on the basis of ideology. Statements on Stem Cell Research The debates on both adult and embryonic stem cell research were dominated by the opposition parties, primarily the Canadian Alliance, which later merged with the Progressive Conservatives to become the Conservative Party, without any significant response from the governing party. It could be implied that the majority's silence demonstrated its unwillingness to assume the political risk of associating itself with the support of controversial research. Whatever the reason, however, the result was a debate largely centered on the moral status of the embryo and based upon the ideologies of the religious right and the god squad of the Liberal party. …

Star polymers: Advances in biomedical applications

Chapter 18 - Application of induced pluripotent stem cells in tissue engineering

The fields of vascular biology and vascular medicine are so intertwined that advances in one predict, explain, or are required for progress in the other. Bypass grafting, which once served as a “bailout” procedure,1 2 is now performed more than 600 000 times annually in the United States. In major part, this increase can be attributed to a surge in understanding of the vascular response to injury. At the same time, the science of vascular biology has been primarily stimulated by the clinical imperative to combat complications that ensue from vascular interventions.3 Thus, when a novel vascular biological finding or cardiovascular medical/surgical technique is presented, we are required to ask the 2-fold question: what have we learned about the biology of the blood vessel, and how might this knowledge be used to enhance clinical perspective and treatment? The innovative method of engineering arterial conduits presented by Campbell et al4 in this issue of Circulation Research presents us with just such a challenge, and I will attempt to deal with the biological and clinical ramifications of this work. Although routinely applied and ubiquitously used, vascular grafting is not without significant constraints and complications.3 Arterial conduits are in limited supply and restricted dimensions. Venous conduits are more abundant but lack vasomotor tone and are prone to thrombotic and hyperplastic occlusion and, less frequently, infection. Veins and arteries must be harvested from sites that leave wounds that can break down or become infected. Synthetic materials do not fare well in small-bore vascular beds and are excessively thrombotic. Graft passivation has been attempted to minimize material-blood interaction by surface modification with coatings of proteins,5 polymer materials, or cells.6 7 Although somewhat successful in limiting thrombosis and hyperplasia, such linings do not provide vascular responsiveness or other biochemical secretory …

National Institutes of Health releases new guidelines for stem cell research