Development of a natural origin, mineralizable, fit-to-shape, nanocomposite and tissue-adhesive hydrogel

• Autor(a) principal: Nunes, Ana Rita Bandarra
• Data de Publicação: 2018
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/25805
• topic: Hydrogels; Bioactivity; Bioadhesion; Self-Healing; Shape-fitting; Shape fixation

A wide plethora of hydrogels are currently suggested as effective tissue regeneration supports. Aa recent trend concerns bioadhesives with the ability to joint tissue parts together. In particular, biomaterials based on mussel-inspired principles have shown high underwater adhesiveness. Applications as tissue sealants, cardiac patches and bone fixating agents have been suggested. However, the development of systems with tuneable physical properties overtime and bioactivity towards cells and tissues is still scarce. With the current limitations associated to bioadhesives in mind, this thesis targets the development of a fit-to-shape biomaterial with bioadhesiveness as well as the ability to acquire a fixed shape overtime, increasing the mended tissues stability. Moreover, the design of this hydrogel-based system also aims at reaching bioactivity to enable both the in situ osseointegration of the bioactive glue (tackling the regeneration of bone defects), localized ionic release and cytocompatibility. Chitosan modified with the DOPA peptide domain was combined with Stöber silica nanoparticles enriched with calcium and phosphate ions to form a composite multifunctional hydrogel. Biomaterials processed with different contents of nanoparticles were tested for their water content, swelling in water and physiological-like solutions, rheological behavior (including stiffness, loss modulus, shear thinning behavior and recovery after structural destruction), ability to adhere biological tissues, and mineralization capability in simulated body fluid (SBF). A stable hydrogel with partial self-recovery upon destruction and shear thinning behavior was obtained by raising the pH of the dissolved polymer to 7. The addition of nanoparticles to the hydrogel led to an increase in storage modulus, and the maintenance of the shear-thinning behavior. Time-dependent oxidation of chitosan’s catechol groups led a time-driven increase of the stiffness of the hydrogels due to the formation of covalent bonds between quinone groups. Hydrogels also showed the ability to bind skin and bone tissues together and increasing amounts of nanoparticles improved the adhesion properties of the materials. While immersed in SBF, the hydrogels promoted the formation of calcium phosphates with Ca/P ratios close the one of hydroxyapatite (~1.67). Overall, the biomaterials developed herein may be used as a biological tissue adhesive with osseointegrative and shape-fixation/time dependent stiffening properties, which may make them promising tissue regeneration devices. Although directed to fixation and regeneration of bone defects, the hydrogel proposed in this thesis may find application in the regeneration of a multiplicity of tissues, including skin and muscle