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      Injectable hydrogel as stem cell scaffolds from the thermosensitive terpolymer of NIPAAm/AAc/HEMAPCL

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          Abstract

          A series of biodegradable thermosensitive copolymers was synthesized by free radical polymerization with N-isopropylacrylamide (NIPAAm), acrylic acid (AAc) and macromer 2-hydroxylethyl methacrylate-poly(ɛ-caprolactone) (HEMAPCL). The structure and composition of the obtained terpolymers were confirmed by proton nuclear magnetic resonance spectroscopy, while their molecular weight was measured using gel permeation chromatography. The copolymers were dissolved in phosphate -buffered saline (PBS) solution (pH = 7.4) with different concentrations to prepare hydrogels. The lower critical solution temperature (LCST), cloud point, and rheological property of the hydrogels were determined by differential scanning calorimetry, ultraviolet-visible spectrometry, and rotational rheometry, respectively. It was found that LCST of the hydrogel increased significantly with the increasing NIPAAm content, and hydrogel with higher AAc/HEMAPCL ratio exhibited better storage modulus, water content, and injectability. The hydrogels were formed by maintaining the copolymer solution at 37°C. The degradation experiment on the formed hydrogels was conducted in PBS solution for 2 weeks and demonstrated a less than 20% weight loss. Scanning electron microscopy was also used to study the morphology of the hydrogel. The copolymer with NIPAAm/AAc/HEMAPCL ratio of 88:9.6:2.4 was bioconjugated with type I collagen for the purpose of biocompatibility enhancement. In -vitro cytotoxicity of the hydrogels both with and without collagen was also addressed.

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          Most cited references 47

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          Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation

          Although mammalian hearts show virtually no ability to regenerate, there is a growing initiative to determine whether existing cardiomyocytes or progenitor cells can be coaxed into eliciting a regenerative response. In contrast to mammals, a number of non-mammalian vertebrate species are able to regenerate their hearts1–3, including the zebrafish4,5, which can fully regenerate its heart following amputation of up to 20% of the ventricle. To directly address the source of newly formed cardiomyocytes during zebrafish heart regeneration, we first established a genetic strategy to lineage-trace cardiomyocytes in the adult fish, based on the Cre/lox system widely used in the mouse6. Using this system, we show here that regenerated heart muscle cells are derived from the proliferation of differentiated cardiomyocytes. Furthermore, we show that proliferating cardiomyocytes undergo limited dedifferentiation characterized by the disassembly of their sarcomeric structure, detachment from one another and expression of regulators of cell cycle progression. Specifically, we show that polo-like kinase1 (plk1) is an essential component of cardiomyocyte proliferation during heart regeneration. Our data provides the first direct evidence for the source of proliferating cardiomyocytes during zebrafish heart regeneration and indicates that stem/progenitor cells are not significantly involved in this process.
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            Heart regeneration.

            Heart failure plagues industrialized nations, killing more people than any other disease. It usually results from a deficiency of specialized cardiac muscle cells known as cardiomyocytes, and a robust therapy to regenerate lost myocardium could help millions of patients every year. Heart regeneration is well documented in amphibia and fish and in developing mammals. After birth, however, human heart regeneration becomes limited to very slow cardiomyocyte replacement. Several experimental strategies to remuscularize the injured heart using adult stem cells and pluripotent stem cells, cellular reprogramming and tissue engineering are in progress. Although many challenges remain, these interventions may eventually lead to better approaches to treat or prevent heart failure.
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              Injectable hydrogels as unique biomedical materials.

              A concentrated fish soup could be gelled in the winter and re-solled upon heating. In contrast, some synthetic copolymers exhibit an inverse sol-gel transition with spontaneous physical gelation upon heating instead of cooling. If the transition in water takes place below the body temperature and the chemicals are biocompatible and biodegradable, such gelling behavior makes the associated physical gels injectable biomaterials with unique applications in drug delivery and tissue engineering etc. Various therapeutic agents or cells can be entrapped in situ and form a depot merely by a syringe injection of their aqueous solutions at target sites with minimal invasiveness and pain. This tutorial review summarizes and comments on this soft matter, especially thermogelling poly(ethylene glycol)-(biodegradable polyester) block copolymers. The main types of injectable hydrogels are also briefly introduced, including both physical gels and chemical gels.
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                Author and article information

                Affiliations
                [1 ]Shanghai Key Laboratory of Advanced Polymeric Materials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, People’s Republic of China
                [2 ]Department of Cardiac Surgery, Zhongshan Hospital, Fudan University and Shanghai Institute of Cardiovascular Diseases, Shanghai, People’s Republic of China
                Author notes
                Correspondence: Yan Xiao, Key Laboratory of Advanced Polymeric, Materials, Key Laboratory for Ultrafine, Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, 130 Meilong Road, 200237 Shanghai, People’s Republic of China, Tel +86 21 64251764, Fax +86 21 64253916, Email yxiao@ 123456ecust.edu.cn . Meidong Lang, Key Laboratory of Advanced Polymeric, Materials, Key Laboratory for Ultrafine, Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, 130 Meilong Road, 200237 Shanghai, People’s Republic of China, Tel +86 21 64253916, Fax +86 21 64253916, Email mdlang@ 123456ecust.edu.cn
                Journal
                Int J Nanomedicine
                Int J Nanomedicine
                International Journal of Nanomedicine
                Dove Medical Press
                1176-9114
                1178-2013
                2012
                2012
                12 September 2012
                : 7
                : 4893-4905
                3446841
                23028218
                10.2147/IJN.S32645
                ijn-7-4893
                © 2012 Lian et al, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                Categories
                Original Research

                Molecular medicine

                thermoresponsive, bioreactive, biodegradable, n-isopropylacrylamide

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