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Multivalent presentation of glycosaminoglycans by their end-on conjugation to star and linear polymers

AuthorsNovoa-Carballal, Ramón; Amaral, S.; Valcárcel, J.; Gomes, M.; Vázquez, José Antonio ; Carretero, A.; Reis, Rui L.; Pashkuleva, I.
Issue Date2019
CitationTerm Sterm Conference (2019)
AbstractGlycosaminoglycans (GAGs) are negatively charged polysaccharides present in the extracellular matrix (ECM) and basement membrane of multicellular organisms. All GAGs but hyaluronic acid (HA) are presented as brush-like molecules –proteoglycans (PG) –in which the polysaccharide is attached by its reducing end to a protein core. PGs are crucial in the regeneration of musculoskeletal tissues, e.g. tendon and cartilage contain essentially hydrogels formed by the self-assembly of GAGs (PGs and HA) with fibers of collagen and elastin. Because PGs isolation is challenging, the common strategy to prepare hydrogel matrixes for stem cell therapy is the covalent crosslinking of one or several ECM components. However, this strategy fails mimicking the real organization of the ECM and hinder the interactions of GAG with other ECM proteins (growth factors, cytokines and chemokines) that is vital for STEM cell differentiation. A morerecent strategy to prepare hydrogels for stem cell therapy is based in the preparation of glycopolymers that mimic PGs.3 However, current approaches for synthesis of PG mimics have two main disadvantages: they either include modification of the GAG’s mainchain thus changing the functional groups responsible for their bioactivity or use oligosaccharides which are, in our opinion, too short to mimic the multivalent interactions governing the GAG bioactivity.4 Herein, we conjugate GAGs via their reducing endto star and linear polymers by oxime reaction thus generating star and brush-like copolymers. We demonstrate that this approach is applicable to high molecular weight GAGs and the main chain of the GAGs is preserved. Our results showed that the multivalent presentation of the GAG preserves their bioactivity and specificity against other ECM components such as growth factors (e.g. FGF-2). The obtained PG mimics can also self-assemble with proteins into microfibers that can serve as ECM mimics
DescriptionPóster.-- Term Sterm 2019 Conference, Braga, 7-8 November
Appears in Collections:(IIM) Comunicaciones congresos
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