Bioengineered hierarchical bonelike compartmentalized microconstructs using nanogrooved microdiscs

• Autor(a) principal: Bjørge, Isabel M.
• Data de Publicação: 2022
• Outros Autores: Sousa, Bárbara M. de, Patrício, Sónia G., Silva, Ana Sofia, Nogueira, Liebert P., Santos, Lúcia F., Vieira, Sandra I., Haugen, Håvard J., Correia, Clara R., Mano, João F
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/34587
• topic: Biophysical cues; Compartmentalization; Liquefied-core capsules; Nanogrooved microdiscs; Bottom-up tissue engineering; Cell self-assembly; Osteogenesis; Prevascularization

Fabrication of vascularized large-scale constructs for regenerative medicine remains elusive since most strategies rely solely on cell self-organization or overly control cell positioning, failing to address nutrient diffusion limitations. We propose a modular and hierarchical tissue-engineering strategy to produce bonelike tissues carrying signals to promote prevascularization. In these 3D systems, disc-shaped microcarriers featuring nanogrooved topographical cues guide cell behavior by harnessing mechanotransduction mechanisms. A sequential seeding strategy of adipose-derived stromal cells and endothelial cells is implemented within compartmentalized, liquefied-core macrocapsules in a self-organizing and dynamic system. Importantly, our system autonomously promotes osteogenesis and construct's mineralization while promoting a favorable environment for prevascular-like endothelial organization. Given its modular and self-organizing nature, our strategy may be applied for the fabrication of larger constructs with a highly controlled starting point to be used for local regeneration upon implantation or as drug-screening platforms.