Where Ideas grow

Bioengineered 3D Microenvironments


Our group focuses on the development of bioengineered microenvironments to promote controlled 3D cell assembly. We intend to recapitulate tissue-specific morphogenesis and differentiation, and understand the impact of microenvironmental signals on these processes. Ultimately, we aim to translate this knowledge into the design of advanced cell-delivery systems for regenerative therapies and 3D in vitro models.



Engineering 3D cell morphogenesis

We have been developing cell-instructive hydrogels, ranging from complex multifunctional hydrogels, to “minimal matrices” containing only the essential biochemical/biomechanical signals for cells to exhibit their unique self-organizing properties and recapitulate tissue-specific morphogenesis and differentiation. By gaining insights into the mechanisms by which cells sense their microenvironment to organize into specific structures, and how this process can be guided by matrix features, we intend to advance the design of ECM-like 3D matrices for different therapeutic applications, from regenerative medicine to cancer.


Microarraying the cell microenvironment

In 3D microenvironments, cells respond to an array of soluble and matrix-associated cues and it is essential to systematically deconstruct their individual contribution and interplay. Yet, such combinatorial studies are very demanding. To address this challenge we are establishing high-throughput screening (HTS) platforms of 3D microarrays, where the combination of different cell-material scenarios into miniaturized specimens will allow assaying numerous variables in a time/cost-effective manner. In particular, it will greatly facilitate the testing of novel hydrogel formulations and optimization of 3D microenvironments.


Current research areas include:

  • The development of pro-angiogenic scaffold-based and scaffold-free microtissues for cell-based regenerative therapy
  • The development of 3D models to analyze the role of the ECM in cancer-related EMT (epithelial-to mesenchymal transitions)


A) Confocal image of human outgrowth endothelial cells (OEC, red) and human mesenchymal stem cells ((MSC) co-entrapped in molecularly-designed alginate microgels. In primed microgels, cells produce abundant amounts of endogenous extracellular matrix (white) and OEC assemble into tubular-like structu

Team Coordinators


Selected Publications

Torres A.L., Bidarra S.J., Pinto M.T., Aguiar P.C., Silva E.A., Barrias C.C.,
Guiding morphogenesis in cell-instructive microgels for therapeutic angiogenesis. Biomaterials154:34-47, 2018. [Journal: Article] [CI: 24] [IF: 10,3]
DOI: 10.1016/j.biomaterials.2017.10.051 SCOPUS: 85032820887. .

Bauman E., Feijão T., Carvalho D.T.O., Granja P.L., Barrias C.C.,
Xeno-free pre-vascularized spheroids for therapeutic applications. Scientific Reports8(1):, 2018. [Journal: Article] [CI: 13] [IF: 4]
DOI: 10.1038/s41598-017-18431-6 SCOPUS: 85040445656. .

Pereira R.F., Barrias C.C., Bártolo P.J., Granja P.L.,
Cell-instructive pectin hydrogels crosslinked via thiol-norbornene photo-click chemistry for skin tissue engineering. Acta Biomaterialia66:282-293, 2018. [Journal: Article] [CI: 51] [IF: 6,6]
DOI: 10.1016/j.actbio.2017.11.016 SCOPUS: 85034850058. .

Bidarra S.J., Oliveira P., Rocha S., Saraiva D.P., Oliveira C., Barrias C.C.,
A 3D in vitro model to explore the inter-conversion between epithelial and mesenchymal states during EMT and its reversion. Scientific Reports6:, 2016. [Journal: Article] [CI: 32] [IF: 4,3]
DOI: 10.1038/srep27072 SCOPUS: 84973343030. .

Maia F.R., Barbosa M., Gomes D.B., Vale N., Gomes P., Granja P.L., Barrias C.C.,
Hydrogel depots for local co-delivery of osteoinductive peptides and mesenchymal stem cells. Journal of Controlled Release189:158-168, 2014. [Journal: Article] [CI: 37] [IF: 7,7]
DOI: 10.1016/j.jconrel.2014.06.030 SCOPUS: 84904318888. .

Maia F.R., Fonseca K.B., Rodrigues G., Granja P.L., Barrias C.C.,
Matrix-driven formation of mesenchymal stem cell-extracellular matrix microtissues on soft alginate hydrogels. Acta Biomaterialia10(7):3197-3208, 2014. [Journal: Article] [CI: 51] [IF: 6]
DOI: 10.1016/j.actbio.2014.02.049 SCOPUS: 84901785690. .

Fonseca K.B., Gomes D.B., Lee K., Santos S.G., Sousa A., Silva E.A., Mooney D.J., Granja P.L., Barrias C.C.,
Injectable MMP-sensitive alginate hydrogels as hMSC delivery systems. Biomacromolecules15(1):380-390, 2014. [Journal: Article] [CI: 66] [IF: 5,8]
DOI: 10.1021/bm4016495 SCOPUS: 84892606344. .

Fonseca K.B., Granja P.L., Barrias C.C.,
Engineering proteolytically-degradable artificial extracellular matrices. Progress in Polymer Science39(12):2010-2029, 2014. [Journal: Review] [CI: 34] [IF: 26,9]
DOI: 10.1016/j.progpolymsci.2014.07.003 SCOPUS: 84910642434. .

Fonseca K.B., Bidarra S.J., Oliveira M.J., Granja P.L., Barrias C.C.,
Molecularly designed alginate hydrogels susceptible to local proteolysis as three-dimensional cellular microenvironments. Acta Biomaterialia7(4):1674-1682, 2011. [Journal: Article] [CI: 101] [IF: 4,9]
DOI: 10.1016/j.actbio.2010.12.029 SCOPUS: 79952189303. .

Bidarra S.J., Barrias C.C., Fonseca K.B., Barbosa M.A., Soares R.A., Granja P.L.,
Injectable in situ crosslinkable RGD-modified alginate matrix for endothelial cells delivery. Biomaterials32(31):7897-7904, 2011. [Journal: Article] [CI: 106] [IF: 7,4]
DOI: 10.1016/j.biomaterials.2011.07.013 SCOPUS: 80051827430. .