Where Ideas Grow

Bioengineered 3D Microenvironments

ABOUT

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.

 

RESEARCH

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

Selected Publications

Feijão T., Neves M.I., Sousa A., Torres A.L., Bidarra S.J., Orge I.D., Carvalho D.T.O., Barrias C.C.,
Engineering injectable vascularized tissues from the bottom-up: Dynamics of in-gel extra-spheroid dermal tissue assembly. Biomaterials279:, 2021. [Journal: Article] [CI: 2] [IF: 15,3]
DOI: 10.1016/j.biomaterials.2021.121222 SCOPUS: 85118349708

Teixeira F.C., Chaves S., Torres A.L., Barrias C.C., Bidarra S.J.,
Engineering a Vascularized 3D Hybrid System to Model Tumor-Stroma Interactions in Breast Cancer. Frontiers in Bioengineering and Biotechnology9:, 2021. [Journal: Article] [CI: 4] [IF: 6,1]
DOI: 10.3389/fbioe.2021.647031 SCOPUS: 85103053615

Carvalho D.T.O., Feijão T., Neves M.I., Da Silva R.M.P., Barrias C.C.,
Directed self-assembly of spheroids into modular vascular beds for engineering large tissue constructs. Biofabrication13(3):, 2021. [Journal: Article] [CI: 6] [IF: 11,1]
DOI: 10.1088/1758-5090/abc790 SCOPUS: 85105354294

Araújo M., Silveira J., Sousa A., Bessa-Gonçalves M., Santos S.G., Barrias C.C.,
A bioinspired multifunctional hydrogel patch targeting inflammation and regeneration in chronic intestinal wounds. Biomaterials Science9(19):6510-6527, 2021. [Journal: Article] [CI: 1] [IF: 7,6]
DOI: 10.1039/d1bm00118c SCOPUS: 85116461216

Campiglio C.E., Bidarra S.J., Draghi L., Barrias C.C.,
Bottom-up engineering of cell-laden hydrogel microfibrous patch for guided tissue regeneration. Materials Science and Engineering C108:, 2020. [Journal: Article] [CI: 12] [IF: 7,3]
DOI: 10.1016/j.msec.2019.110488 SCOPUS: 85075568685

Araújo M., Bidarra S.J., Alves P.M., Valcarcel J., Vázquez J.A., Barrias C.C.,
Coumarin-grafted blue-emitting fluorescent alginate as a potentially valuable tool for biomedical applications. Journal of Materials Chemistry B8(4):813-825, 2020. [Journal: Article] [CI: 10] [IF: 6,3]
DOI: 10.1039/c9tb01402k SCOPUS: 85078683860

Torres A.L., Bidarra S.J., Vasconcelos D.P., Barbosa J.N., Silva E.A., Nascimento D.S., Barrias C.C.,
Microvascular engineering: Dynamic changes in microgel-entrapped vascular cells correlates with higher vasculogenic/angiogenic potential. Biomaterials228:, 2020. [Journal: Article] [CI: 18] [IF: 12,5]
DOI: 10.1016/j.biomaterials.2019.119554 SCOPUS: 85074166551

Barros da Silva P., Coelho M., Bidarra S.J., Neves S.C., Barrias C.C.,
Reshaping in vitro Models of Breast Tissue: Integration of Stromal and Parenchymal Compartments in 3D Printed Hydrogels. Frontiers in Bioengineering and Biotechnology8:, 2020. [Journal: Article] [CI: 6] [IF: 5,9]
DOI: 10.3389/fbioe.2020.00494 SCOPUS: 85087017058

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: 34] [IF: 10,3]
DOI: 10.1016/j.biomaterials.2017.10.051 SCOPUS: 85032820887

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: 41] [IF: 4,3]
DOI: 10.1038/srep27072 SCOPUS: 84973343030

Ongoing Projects

Uma estratégia de bioengenharia para mobilizar a plasticidade endotelial e promover a revascularização terapêutica de tecido isquémico
Reference: PTDC/BTM-ORG/5154/2020
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 29-MAR-21 to 28-MAR-24
Extracellular vesicles mediate cryptic infections in the human bone marrow and spleen in Plasmodium
Reference: la Caixa HR21-00171
Proponent: Institut de Salut Gobal de Barcelona - ISGlobal
Sponsor: "la Caixa" Foundation
From 01-SEP-21 to 31-AUG-24