RESUMO
Bioprinting is a precise layer-by-layer manufacturing technology utilizing biomaterials, cells, and sometimes growth factors for the fabrication of customized three-dimensional (3D) biological constructs. In recent years, it has gained considerable interest in various biomedical studies. However, the translational application of bioprinting is currently impeded by the lack in efficient techniques for blood vessel fabrications. In this report, by systematically studying the previously reported phenomenon, interfacial polyelectrolyte complexation, an efficient blood vessel bioprinting technique based on the phenomenon, was proposed and subsequently investigated. In this technique, anionic hyaluronate and cationic lysine-based peptide amphiphiles were placed concentrically to bioprint with human umbilical endothelial cells for the fabrication of biological tubular constructs. These constructs demonstrated clear vascular features, which made them highly resemble blood vessels. In addition, to optimize the bioactivity of the printed constructs, this report also, for the first time, studied peptide sequencing's effect on the biocompatibility of the polyelectrolyte-peptide amphiphile complex. All these studies conducted in the report are highly relevant and interesting for research in vascular structure fabrication, which will eventually be beneficial for translational application development of bioprinting.
Assuntos
Bioimpressão , Alicerces Teciduais , Humanos , Alicerces Teciduais/química , Polieletrólitos , Células Endoteliais , Bioimpressão/métodos , Impressão Tridimensional , Engenharia Tecidual/métodosRESUMO
Hyaluronic acid (HA)-based biomaterials have demonstrated only limited in vivo stability as a result of rapid degradation by hyaluronidase and reactive oxidative species. The green tea catechin, (-)-epigallocatechin-3-O-gallate (EGCG), has received considerable attention because of its powerful antioxidant and enzyme-inhibitory activities. We describe here the synthesis of HA-EGCG conjugate using a thiol-mediated reaction and its use for the preparation of a long-lasting injectable hydrogel. HA-EGCG conjugates with tunable degrees of substitution were synthesized by the nucleophilic addition reaction between EGCG quinone and thiolated HA under mild conditions. Contrary to unmodified HA, the conjugates exhibited free radical scavenging and hyaluronidase-inhibitory activities. Peroxidase-catalyzed coupling reaction between EGCG moieties was employed to produce in situ forming HA-EGCG hydrogel with surprisingly high resistance to hyaluronidase-mediated degradation. When injected subcutaneously in mice, HA-EGCG hydrogel was retained much longer than HA-tyramine hydrogel with minimal inflammation.