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      Comparative studies of thermogels in preventing post-operative adhesions and corresponding mechanisms

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          Abstract

          Thermogelling PLGA–PEG–PLGA, PCGA–PEG–PCGA, and PCL–PEG–PCL triblock copolymers and their efficacies of prevention of post-surgical peritoneal adhesions in rabbits were investigated and compared.

          Post-surgical peritoneal adhesions constitute a classic problem in surgery, and thus anti-adhesion materials are much required. In this study, a series of polyester–PEG–polyester triblock copolymers with different biodegradable polyester compositions were synthesized, their properties were examined, and the in vivo efficacies as anti-adhesion biomaterials were evaluated in a comparative way for the first time. These samples not only exhibited various morphologies in the bulk state, but also possessed different stabilities in the sol state. All the polymer aqueous solutions with appropriate compositions and concentrations underwent sol–gel transitions with increase of temperature and formed semi-solid hydrogels at body temperature. The efficacy of PEG/polyester thermogels (25 wt%) for preventing post-operative abdominal adhesions was investigated and compared in a rabbit model of sidewall defect-bowel abrasion. Different efficacies of anti-adhesion were observed, possible mechanisms were discussed, and the importance of viscoelasticity was suggested for the first time. These results illustrated that appropriate properties of PEG/polyester thermogels including viscoelastic matrix, hydrophilic surface and moderate in vivo persistence played crucial roles in enabling an effective device to prevent post-surgical peritoneal adhesions.

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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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            Biodegradable block copolymers as injectable drug-delivery systems.

            Polymers that display a physicochemical response to stimuli are widely explored as potential drug-delivery systems. Stimuli studied to date include chemical substances and changes in temperature, pH and electric field. Homopolymers or copolymers of N-isopropylacrylamide and poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (known as poloxamers) are typical examples of thermosensitive polymers, but their use in drug delivery is problematic because they are toxic and non-biodegradable. Biodegradable polymers used for drug delivery to date have mostly been in the form of injectable microspheres or implant systems, which require complicated fabrication processes using organic solvents. Such systems have the disadvantage that the use of organic solvents can cause denaturation when protein drugs are to be encapsulated. Furthermore, the solid form requires surgical insertion, which often results in tissue irritation and damage. Here we report the synthesis of a thermosensitive, biodegradable hydrogel consisting of blocks of poly(ethylene oxide) and poly(L-lactic acid). Aqueous solutions of these copolymers exhibit temperature-dependent reversible gel-sol transitions. The hydrogel can be loaded with bioactive molecules in an aqueous phase at an elevated temperature (around 45 degrees C), where they form a sol. In this form, the polymer is injectable. On subcutaneous injection and subsequent rapid cooling to body temperature, the loaded copolymer forms a gel that can act as a sustained-release matrix for drugs.
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              Hydrogels for protein delivery.

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                Author and article information

                Journal
                BSICCH
                Biomater. Sci.
                Biomater. Sci.
                Royal Society of Chemistry (RSC)
                2047-4830
                2047-4849
                2014
                2014
                : 2
                : 8
                : 1100-1109
                Article
                10.1039/C4BM00029C
                6948e9bb-c68c-41da-92ca-2573fd927211
                © 2014
                History

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