Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 14, Issue 17, Pages 19116-19128Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.2c01161
Keywords
biophysical cues; compartmentalization; liquefied-core capsules; nanogrooved microdiscs; bottom-up tissue engineering; cell self-assembly; osteogenesis; prevascularization
Funding
- Portuguese Foundation for Science and Technology (FCT) [SFRH/BD/129224/2017, SFRH/BD/141523/2018, 2020.06525.BD]
- European Research Council [ERC-2014-ADG-669858]
- national funds (OE) through (FCT/MCTES) [PTDC/BTM-MAT/3201/2020, PTDC/BTM-MAT/31064/2017, PTDC/BTM-MAT/31210/2017, PTDC/BTM-MAT/29830/2017]
- Programa Operacional Competitividade e Internacionalizacao, in the component FEDER [POCI-01-0145-FEDER-031064, POCI-01-0145-FEDER-031210]
- Portuguese Mass Spectrometry Network [ROTEIRO/0028/2013, LISBOA-01-0145-FEDER-022125, POCI-01-0145-FEDER-022122, UIDB/50011/2020, UIDP/50011/2020]
- iBiMED [UID/BIM/04501/2019]
- FCT/MEC
- FEDER
- [2020.00366.CEECIND]
- [2020.04344.CEECIND]
- Fundação para a Ciência e a Tecnologia [PTDC/BTM-MAT/3201/2020, PTDC/BTM-MAT/31210/2017, PTDC/BTM-MAT/31064/2017, 2020.06525.BD, SFRH/BD/141523/2018, SFRH/BD/129224/2017, PTDC/BTM-MAT/29830/2017] Funding Source: FCT
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A modular and hierarchical tissue-engineering strategy is proposed to fabricate vascularized large-scale constructs. The strategy promotes prevascularization and autonomously enhances osteogenesis and construct's mineralization.
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.
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