epithelial, connective, and nerve tissues of vertebrates. It is designated as a glycosaminoglycan. [1] Glycosaminoglycans are composed of disaccharide blocks of N-acetylgalactosamine or N-acetylglucosamine, (amino sugars) and uronic sugars such as glucuronic acid, iduronic acid or galactose. This group of heteropolysaccharides comprises HA, chondroitin sulfates, dermatan sulfate, heparin and heparin sulfates whose sulfation degree is less than that of heparin. Unlike other glycosaminoglycans, hyaluronan is not sulfated and it is self-standing, i.e. without an association with a core protein. [2] It was isolated in 1934 by Meyer and Palmer from bovine vitreous humor. [3] The polymer chain of hyaluronan comprises repeating disaccharide units where the pyranose rings are connected by β-1,3 bonds. The repeating units are bonded with a β-1,4 glycosidic bond within the chain between N-acetyl-D-glucosamine and D-glucuronic acid. At physiological pH each glucuronate unit, associated with its carboxylate group, carries an anionic charge. The hundreds of negative charges are fixed to each chain. These anionic groups are balanced with mobile cations such as Na + , K + , Ca 2+ and Mg 2+ . During ionization of D-glucuronic acid with the carboxylic groups, the charges influence the organization of the chains and their interactions with their surroundings. In turn, they are affected by pH and ionic strength. The chain organization and charge directly affect the solubility in water, since hyaluronan is water-insoluble when convertedAs an Extracellular Matrix (ECM) component, Hyaluronic acid (HA) plays a multi-faceted role in cell migration, proliferation and differentiation at micro level and system level events such as tissue water homeostasis. Among its biological functions, it is known to interact with cytokines and contribute to their retention in ECM microenvironment. In addition to its biological functions, it has advantageous physical properties which result in the industrial endeavors in the synthesis and extraction of HA for variety of applications ranging from medical to cosmetic. Recently, HA and its derivatives have been the focus of active research for applications in biomedical device coatings, drug delivery systems and in the form of scaffolds or cell-laden hydrogels for tissue engineering. A specific reason for the increase in use of HA based structures is their immunomodulatory and regeneration inducing capacities. In this context, this article reviews recent literature on modulation of the implantable biomaterial microenvironment by systems based on HA and its derivatives, particularly hydrogels and microscale coatings that are able to deliver cytokines in order to reduce the adverse immune reactions and promote tissue healing.

Advances in nanoparticle (NP) production and demand for control over nanoscale systems have had significant impact on tissue engineering and regenerative medicine (TERM). NPs with low toxicity, contrasting agent properties, tailorable characteristics, targeted/stimuli-response delivery potential, and precise control over behavior (via external stimuli such as magnetic fields) have made it possible their use for improving engineered tissues and overcoming obstacles in TERM. Functional tissue and organ replacements require a high degree of spatial and temporal control over the biological events and also their real-time monitoring. Presentation and local delivery of bioactive (growth factors, chemokines, inhibitors, cytokines, genes etc.) and contrast agents in a controlled manner are important implements to exert control over and monitor the engineered tissues. This need resulted in utilization of NP based systems in tissue engineering scaffolds for delivery of multiple growth factors, for providing contrast for imaging and also for controlling properties of the scaffolds. Depending on the application, materials, as polymers, metals, ceramics and their different composites can be utilized for production of NPs. In this review, we will cover the use of NP systems in TERM and also provide an outlook for future potential use of such systems.

(2017) Generation of anti-inflammatory macrophages for implants and regenerative medicine using self-standing release systems with a phenotype-fixing cytokine cocktail formulation. Acta Biomaterialia . ISSN 1878-7568 Access from the University of Nottingham repository: http://eprints.nottingham.ac.uk/40797/1/2017%2001%2016_Ryabov_Acta %20Biomaterialia.pdf Copyright and reuse:The Nottingham ePrints service makes this work by researchers of the University of Nottingham available open access under the following conditions. This article is made available under the University of Nottingham End User licence and may be reused according to the conditions of the licence. For more details see: http://eprints.nottingham.ac.uk/end_user_agreement.pdf A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription.For more information, please contact eprints@nottingham.ac.uk facilitated wound closure by human fibroblasts in co-culture conditions. Using a model for induction of inflammation by LPS we have shown that the M2Ct phenotype is stable for 12 days. However, in the absence of M2Ct in the medium macrophages underwent rapid pro-inflammatory re-programming upon IFNg stimulation. Therefore, loading and release of the cytokine cocktail from a self-standing, transferable Gelatin/Tyraminated Hyaluronic acid based release system was developed to stabilize macrophage phenotype for in vivo application in implantation and tissue engineering. The M2Ct cytokine cocktail retained its anti-inflammatory activity in controlled release conditions. Our data indicate that the direct application of a potent M2 inducing cytokine cocktail in a transferable release system can significantly improve the long term functionality of biomedical devices by decreasing proinflammatory cytokine secretion and increasing the rate of wound healing.