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FunctionHeAling - Hyaluronan-based multifunctional hydrogels for wound healing

Principal investigator: Helena AZEVEDO
Funding source(s): WHRI ACADEMY Marie Curie cofund/ European Union
 Start: 01-10-2014  /  End: 30-09-2015
Directly incurred staff: Daniela Ferreira

Hyaluronan (HA) is a natural polymer made of N-acetylglucosamine and glucuronic acid. As one of the main constituents of skin extracellular matrix (ECM), offers many unique advantages as a starting material to for developing skin substitutes. The focus of this project is to develop hyaluronan-based multifunctional hydrogels capable of rapidly gelling in situ under physiological conditions. We aim to use an enzyme-triggered crosslinking mechanism to cross-link in situ the developed hydrogel by using the transglutaminase factor XIIIa. The system will integrate HA macromers conjugated with peptide substrates for factor XIIIa (TG-Lys and TG-Gln) and others including the factor XIIa substrate and a biological epitope (e.g. TG-Gln-RGDS). Peptide substrates will be rationally designed, synthesized and coupled to acrylate-HA. These polymerpeptide conjugates will then be crosslinked by factor XIIIa to rapidly form an hydrogel under physiological conditions. This proposal is divided in three work packages, starting from the design and synthesis of the hydrogel building blocks to cell culture studies and in vitro characterization for it potential use in wound healing. The proposed strategy will present a way to develop a platform that mimics skin ECM microenvironment in both composition and crosslinking chemistry, and has the potential to recapitulate the instructive signals that ultimately promote tissue regeneration. The tuneable nature of the peptides used in this project makes the hydrogel developed in the proposed work an innovative approach for many different applications from cell delivery to growth factor reservoir system which makes the proposed hydrogel a potential candidate for a variety of applications beyond wound healing.