@article {20220, title = {Convection as a driving mechanism for gradients formation in interfaced gels for 3-D tissue interfaces}, journal = {Chem2Nature Summer School 2018}, year = {2018}, month = {2018-06-04 00:00:00}, address = {Porto, Portugal}, abstract = {

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.

References

[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.

Acknowledgments

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 - Solu{\c c}{\~o}es de Automa{\c c}{\~a}o e Rob{\'o}tica for the support with bioreactor development, to Jo{\~a}o Costa (3B{\textquoteright}s Research Group) for the assistance with dynamic mechanical analysis, to I. F. Cengiz (3B{\textquoteright}s Research Group) and Filipe Carvalho (3B{\textquoteright}s Research Group) for their help with material shipment and micro-CT analysis, to Alessandro Tocchio (BAMM Lab) for their helpful and inspiring discussions.

Keywords

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

}, keywords = {Anisotropy, biochemical gradient, Heterotypic tissues, Micro-particles gradient}, url = {https://chem2nature.eu/}, author = {Canadas, R. F. and da Silva Morais, A. and Patr{\'\i}cio, P. and Gasperini, L. and Vilela, C. A. and Costa, J. B. and Ara{\'u}jo, N. A. M. and Reis, R. L. and Marques, A. P. and Oliveira, J. M.} }