Injectable leachable-free hydrogel foams for cell delivery

• Autor(a) principal: Salvador, Tânia Raquel Ferreira
• Data de Publicação: 2019
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/30102
• topic: Tissue engineering; Microporosity; Hydrogels; Foams

Microporosity is often associated with pre-formed scaffolds with pre-defined shapes that are unable to be injected and to withstand cell encapsulation during its manufacturing process. Injectable hydrogels are widely applied in regenerative medicine, since they are capable of withstanding cell encapsulation and to undergo in situ physical or chemical crosslinking. However, the diffusion of nutrients is often limited to 100 – 200 μm within bulk hydrogels with clinically relevant dimensions, leading to the appearance of necrotic cores, or uneven cell response. In addition, the migration of cells is also impaired due to hydrogels’ nanometric pore sizes. Therefore, the combination of injectable hydrogels with microporous structures is desired; however, the techniques currently used to achieve this feature often rely on the use of solid or liquid leaching agents, which may be toxic or locally modulate the host implantation site in unexpected manners. Therefore, the main goal of this project is the development of a cellladen injectable gelatin methacryloyl (GelMA) hydrogel foam, that do not require the use of leaching agents and that is able to be injected and undergo in situ photocrosslinking. GelMA hydrogel foams were prepared by a newly developed syringe foaming technique using a single polymer formulation. When exposed to UV irradiation, the structure of the foam was successfully maintained due to photocrosslinking. Three different conditions were studied: (1) GelMA hydrogels without the introduction of air bubbles (H7s); (2) GelMA foams (F7s) and (3) pre-crosslinked foams in which cells were added after a pre-crosslinking step (F5s2s), aiming at the development of a milder process. Water uptake studies demonstrated that both foam formulations have a high capacity of water uptake and water retention compared to H7s. Moreover, molecule release studies indicated that foams have a lower value of FITCdextran release, serving as potential long-term reservoirs of medium-sized molecules. Cell viability assays showed that H7s samples present a highly proliferative area at its surface after 7 days of cell culture, and liquified core at the center of the biomaterial. In both foam formulations, cell viability was demonstrated throughout the whole structures at all studied time points. Moreover, cell metabolic activity after 7 days of cell culture was higher in F5s2s foams, compared to H7s and F7s conditions. The technique reported here allowed a leachable-free fabrication of injectable fitto-shape GelMA foams combined living cells using a single material formulation. In addition, this strategy allows the in situ crosslinking of the GelMA foam structures in tissue defects.