One-Step Rapid Fabrication of Cell-Only Living Fibers

resumo

Cellular aggregates are used as relevant regenerative building blocks, tissue models, and cell delivery platforms. Biomaterial-free structures are often assembled either as 2D cell sheets or spherical microaggregates, both incompatible with free-form deposition, and dependent on challenging processes for macroscale 3D upscaling. The continuous and elongated nature of fiber-shaped materials enables their deposition in unrestricted multiple directions. Cellular fiber fabrication has often required exogenously provided support proteins and/or the use of biomaterial-based sacrificial templates. Here, the rapid (<24 h) assembly of fiberoids is reported: living centimeter-long scaffold-free fibers of cells produced in the absence of exogenous materials or supplements. Adipose-derived mesenchymal stem cell fiberoids can be easily modulated into complex multidimensional geometries and show tissue-invasive properties while keeping the secretion of trophic factors. Proangiogenic properties studied on a chick chorioallantoic membrane in an ovo model are observed for heterotypic fiberoids containing endothelial cells. These micro-to-macrotissues may find application as morphogenic therapeutic and tissue-mimetic building blocks, with the ability to integrate 3D and 4D full biological materials.

palavras-chave

EXTRACELLULAR-MATRIX; ANGIOGENESIS; VASCULARIZATION; MORPHOGENESIS; SPHEROIDS; HYDROGELS; HEALTH

categoria

Chemistry; Science & Technology - Other Topics; Materials Science; Physics

autores

Sousa, AR; Martins-Cruz, C; Oliveira, MB; Mano, JF

nossos autores

agradecimentos

A.R.S., C.M.-C., and M.B.O. contributed equally to this work. This work was supported by the Programa Operacional Competitividade e Internacionalizacao, in the component FEDER, and by national funds (OE) through FCT/MCTES, in the scope of the projects TranSphera (PTDC/BTM-ORG/30770/2017). This work was also developed within the scope of the project CICECO-Aveiro Institute of Materials, POCI-01-0145-FEDER-007679 (FCT Ref. UID/CTM/50011/2013), financed by national funds through the FCT/MEC and when appropriate cofinanced by FEDER under the PT2020 Partnership Agreement. M.B.O. acknowledges the individual contract CEECIND/03605/2017. Human adipose-derived mesenchymal stem cells (hASCs) were purchased from ATCC, USA. CAM assay experiments were performed according to European Directive 2010/63/EU and the national Decreto-Lei no113/2013; specific ethical approval is not required. Paulo Laranjeira is acknowledged for his support in the preparation of Videos S2-S5 (Supporting Information).

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