creating a
healthier future

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

Orge I.D., Nogueira Pinto H., Silva M.A., Bidarra S.J., Ferreira S.A., Calejo I., Masereeuw R., Mihăilă S.M., Barrias C.C.
Vascular units as advanced living materials for bottom-up engineering of perfusable 3D microvascular networks. Bioactive Materials38:499-511, 2024. [Journal: Article] [IF: 18 (*)]
DOI: 10.1016/j.bioactmat.2024.05.021 SCOPUS: 85193041211

Barros da Silva P., Oliveira R.J.A., Araújo M., Caires H.R., Bidarra S.J., Barrias C.C.
An integrative alginate-based 3D in vitro model to explore epithelial-stromal cell dynamics in the breast tumor microenvironment. Carbohydrate Polymers342:, 2024. [Journal: Article] [IF: 10.7 (*)]
DOI: 10.1016/j.carbpol.2024.122363 SCOPUS: 85195551038

Carvalho E.D., Morais M.R.G., Pêgo A.P., Barrias C.C., Araújo M.
The interplay between chemical conjugation and biologic performance in the development of alginate-based 3D matrices to mimic neural microenvironments. Carbohydrate Polymers323:, 2024. [Journal: Article] [CI: 2] [IF: 10.7 (*)]
DOI: 10.1016/j.carbpol.2023.121412 SCOPUS: 85173151997

Magalhães M.V., Débera N., Pereira R.F., Neves M.I., Barrias C.C., Bidarra S.J.
In situ crosslinkable multi-functional and cell-responsive alginate 3D matrix via thiol-maleimide click chemistry. Carbohydrate Polymers337:, 2024. [Journal: Article] [IF: 10.7 (*)]
DOI: 10.1016/j.carbpol.2024.122144 SCOPUS: 85190291263

Neves M.I., Magalhães M.V., Bidarra S.J., Moroni L., Barrias C.C.
Versatile click alginate hydrogels with protease-sensitive domains as cell responsive/instructive 3D microenvironments. Carbohydrate Polymers320:, 2023. [Journal: Article] [CI: 2] [IF: 10.7]
DOI: 10.1016/j.carbpol.2023.121226 SCOPUS: 85165717522

Neves M.I., Bidarra S.J., Magalhães M.V., Torres A.L., Moroni L., Barrias C.C.
Microstructured click hydrogels for cell contact guidance in 3D. Materials Today Bio19:, 2023. [Journal: Article] [CI: 4] [IF: 8,2 (*)]
DOI: 10.1016/j.mtbio.2023.100604 SCOPUS: 85150054257

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: 11] [IF: 15,3]
DOI: 10.1016/j.biomaterials.2021.121222 SCOPUS: 85118349708

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: 10] [IF: 11,1]
DOI: 10.1088/1758-5090/abc790 SCOPUS: 85105354294

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: 30] [IF: 12,5]
DOI: 10.1016/j.biomaterials.2019.119554 SCOPUS: 85074166551

Neves S.C., Moroni L., Barrias C.C., Granja P.L.
Leveling Up Hydrogels: Hybrid Systems in Tissue Engineering. Trends in Biotechnology38(3):292-315, 2020. [Journal: Review] [CI: 73] [IF: 19,5]
DOI: 10.1016/j.tibtech.2019.09.004 SCOPUS: 85075891574

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

Ongoing Projects

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 01-APR-25
Angiogenesis in tissue engineering: from computational approach to clinical application
Reference: PTDC/EME-APL/3058/2021
Proponent: INEGI
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-JAN-22 to 31-JUL-25
MyoTextile - Living cell-based 3D biotextiles for skeletal muscle tissue regeneration
Reference: ON/ICORS Kick-Starter Grant 2022 n? 22-287
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: ON Foundation
From 01-MAY-23 to 31-DEC-24
MRD-on-chip: Exploring the emergence of minimal residual disease and relapse in Acute Myeloid Leukaemia
Reference: 2022.05195.PTDC
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 12-MAR-23 to 31-DEC-24
Bioengineering living materials for personalized treatment of osteoradionecrosis patients
Reference: Premio Alfredo da Silva 2023 - BioMade4U
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: Fundação Amélia de Mello
From 01-JAN-24 to 31-DEC-25
Training for Organoids modelling Physiology and Pathology in the human gastrointestinal tract
Reference: HORIZON-TMA-MSCA-DN - GA 101119911
Sponsor: CE - Comissão Europeia
From 01-NOV-23 to 31-OCT-27