Convection as a driving mechanism for gradients formation in interfaced gels for 3-D tissue interfaces

last updated: 2020-02-02
ProjectHierarchiTech :: publications list
TitleConvection as a driving mechanism for gradients formation in interfaced gels for 3-D tissue interfaces
Publication TypeComunications - Poster
Year of Publication2018
AuthorsCanadas R. F., da Silva Morais A., Patrício P., Gasperini L., Vilela C. A., Costa J. B., Araújo N. A. M., Reis R. L., Marques A. P., and Oliveira J. M.

In nature, gradients of 3-D tissue interfaces organized in functional patterns are commonly found[1] and used in diversified fields such as drug delivery, micro-fabrication, drug development, and tissue engineering. While diverse fabrication techniques based on material science, micro-scale engineering, and microfluidics have been used to synthesize such microenvironments[2,3], mimicking native organized gradients is still a challenge. Here, we describe a strategy to obtain a spatial-temporal control over a 3-D cellular environment as it is specially required when a hierarchical tissue has to be formed in vitro. Using 3-D gradient constructs in both, isotropic and anisotropic porous architectures, tissue organization and its spatial composition were controlled. Moreover, the patterned structure was biologically enhanced using an interconnected dual-chamber bioreactor that allowed a simultaneous perfusion of different cell culture media. As proof of concept, an in vitro 3-D osteochondral (OC) tissue model was developed, being evaluated the co-differentiation of stem cells onto the structures. Results showed significant differences in the expression of cartilage and bone markers along a single construct as it occurs in the native osteochondral interface. Additionally, a spatial and temporal induction of endothelization was controlled due to the localized perfusion of pro-angiogenic conditions in a specific region of the 3-D construct, as observed in a native hyaline cartilage. So, the spatial-temporal control over cell phenotype and endothelization described in this study opens-up new solutions for tissue interfaces and angiogenesis in tissue engineering with broad applications in drug testing and regenerative medicine.



[1]         J. B. Gurdon, P.-Y. Bourillot, Nature 2001, 413, 797.

[2]         F. Xu, C.-A. M. Wu, V. Rengarajan, T. D. Finley, H. O. Keles, Y. Sung, B. Li, U. A. Gurkan, U. Demirci, Adv. Mater. 2011, 23, 4254.

[3]         R. F. Canadas, T. Ren, A. Tocchio, A. P. Marques, J. M. Oliveira, R. L. Reis, U. Demirci, Biomaterials 2018, 181, 402.



The authors are grateful for the FCT distinctions attributed to R. F. Canadas (SFRH/BD/92565/2013), who was awarded a PhD scholarship, and to J. M. Oliveira (IF/00423/2012 and IF/01285/2015). The authors acknowledge that this material and collaboration is based in part upon work supported by FLAD. This work was in part supported by European Research Council Grant agreement ERC-2012-ADG 20120216-321266 for project ComplexiTE. The authors also thank SAR - Soluções de Automação e Robótica for the support with bioreactor development, to João Costa (3B’s Research Group) for the assistance with dynamic mechanical analysis, to I. F. Cengiz (3B’s Research Group) and Filipe Carvalho (3B’s Research Group) for their help with material shipment and micro-CT analysis, to Alessandro Tocchio (BAMM Lab) for their helpful and inspiring discussions.



Heterotypic tissues; Biochemical gradient; Micro-particles gradient; Anisotropy

Conference NameChem2Nature Summer School 2018
Date Published2018-06-04
Conference LocationPorto, Portugal
KeywordsAnisotropy, biochemical gradient, Heterotypic tissues, Micro-particles gradient
Peer reviewedyes

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