Autor(es):
Bjørge, Isabel M. ; 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
Data: 2022
Identificador Persistente: http://hdl.handle.net/10773/34587
Origem: RIA - Repositório Institucional da Universidade de Aveiro
Assunto(s): Biophysical cues; Compartmentalization; Liquefied-core capsules; Nanogrooved microdiscs; Bottom-up tissue engineering; Cell self-assembly; Osteogenesis; Prevascularization
Descrição
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.