RESUMEN
We report a simple method of preparing autonomous and rapid self-adhesive hydrogels and their use as building blocks for additive manufacturing of functional tissue scaffolds. Dynamic cross-linking between 2-aminophenylboronic acid-functionalized hyaluronic acid and poly(vinyl alcohol) yields hydrogels that recover their mechanical integrity within 1 min after cutting or shear under both neutral and acidic pH conditions. Incorporation of this hydrogel in an interpenetrating calcium-alginate network results in an interfacially stiffer but still rapidly self-adhesive hydrogel that can be assembled into hollow perfusion channels by simple contact additive manufacturing within minutes. Such channels withstand fluid perfusion while retaining their dimensions and support endothelial cell growth and proliferation, providing a simple and modular route to produce customized cell scaffolds.
Asunto(s)
Adhesivos/química , Hidrogeles/química , Ingeniería de Tejidos/métodos , Andamios del Tejido , Ácidos Borónicos/química , Reactivos de Enlaces Cruzados/química , Células Epiteliales/citología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Ácido Hialurónico/química , Concentración de Iones de Hidrógeno , Alcohol Polivinílico/químicaRESUMEN
Using a well-defined poly(2,2-bis(hydroxymethyl)propanoic acid) dendrimer scaffold, a series of G1 to G3 dendrons is functionalized at the periphery with alkynes to enable "Click" functionalization via the copper-catalyzed alkyne-azide cycloaddition (CuAAC). The resulting dendrons are further functionalized at the core with a dipicolylamine (DPA) moiety to enable radiolabeling with 99m Tc for molecular imaging applications. Efficient CuAAC coupling is achieved using an azide-functionalized triethylene glycol monomethyl ether (TEG-N3 ). Removal of copper from the DPA ligand is successfully performed on G1 and G2 dendrimers prior to radiolabeling with 99m Tc. Radiolabeling of the G3 dendrimer is accomplished via transmetallation of the [CuDPA]2+ ligand with 99m Tc, further demonstrating the feasibility of the synthetic strategies in the preparation of dendritic imaging agents. Subsequent attachment of an acyloxymethyl ketone (AOMK) derivative for targeting of cathepsin B is also explored. Despite demonstrating the ability to ligate multiple AOMK ligands, the AOMK-dendrimer conjugates are not able to bind to cathepsin B, which may be attributed to steric hindrance at the dendrimer periphery.