Biocarrier - Biomaterials for Multistage Drug and Cell Delivery

ABOUT

The overall aim of the group is to develop molecularly-designed, cell-instructive biomaterials as 3D artificial matrices for the delivery of drugs, biomolecules, genes and cells with implications in tissue regeneration and cancer diagnosis and treatment.

The group has specialized in directing and mechanistically following cell behavior in engineered 3D microenvironments toward the development of cell-instructive injectable biomaterials for tissue regeneration. Hydrogels were functionalized with cell-interactive peptides in order to reproduce some essential features of the extracellular matrix, namely cell adhesion, proteolytic degradation and guided cell differentiation. They are being investigated as models to study cell behavior in 3D conditions in regenerative therapies (bone, vascular and skin) and degenerative conditions (cancer).

The group is also developing integrative approaches, combining molecularly-designed 3D matrices with advanced high-throughput screening (HTS) tools to design artificial 3D cell culture platforms to answer questions of fundamental biological and of clinical importance, as well as advanced in vitro cell models of human mucosa (gastric and intestinal) as tools to study the transport of biopharmaceuticals and nanoparticles.

Biofunctionalized nanoparticulate systems are also being investigated with application in the pharmaceutical and biomedical fields, to provide the controlled and targeted delivery of bioactive molecules in therapies for infectious diseases (e.g. HIV) and cancer, as well as diagnosis (e.g. cancer).



RESEARCH

The group has developed molecularly designed natural polymers (e.g. cellulose, alginate, chitosan and pectin) as artificial 3D extracellular matrices (ECM) by mimicking some of its key natural features such as cell adhesion ability, proteolytic susceptibility and cell signaling. Angiogenesis is also a main interest and we have contributed to elucidate the crosstalk between mature and progenitor vascular cells (endothelial cells and fibroblasts) and tissue cells (bone and mesenchymal stem cells) in order to promote vascularization of newly formed tissues. The group has also been having an impact on nanomedicine with the development of the following functionalized nanoparticulate systems, with special focus on infection and cancer: vaginal mucosa nanodevices for prevention of HIV; chitosan nanoparticles capable of overcoming macrophage phagocytosis in vitro; nanoparticles selectively targeting EGFR overexpressing cancer cells; dendrimer-based nanoparticles for gene therapy; discovery of new specific biomarkers for gastric cancer, namely CD44v6; development of a triple in vitro intestinal model for the study of the permeability of proteins and nanoparticles.

 

SELECTED PUBLICATIONS

Fonseca KB, Granja PL, Barrias CC. Engineering proteolytically-degradable artificial extracellular matrices. Progress in Polymer Science 2014 (In Press). IF=26.383

A Sosnik, J Neves, B Sarmento. Mucoadhesive polymers in the design of nano-drug delivery systems for administration by non-parenteral routes: A review. Progress in Polymer Science 2014 (In press). (IF: 26.383)

Shrestha N, Shahbazi M-A, Araujo F, Zhang H, Mäkilä E, Sarmento B, Salonen J, Hirvonen J, Santos HA. Chitosan-modified porous silicon microparticles for enhanced permeability of insulin across intestinal cell monolayers, Biomaterials 2014;35:7172-9. (IF: 8.312)

Maia FR, Barbosa M, Gomes DB, Vale N, Gomes P, Granja PL, Barrias CC. Hydrogel depots for local co-delivery of osteoinductive peptides and mesenchymal stem cells. Journal of Controlled Release 2014;189:158–168. (IF=7.261)

Lopes D, Nunes C, Martins MC, Sarmento B, Reis S. Eradication of Helicobacter pylori: Past, present and future. Journal of Controlled Release 2014;189:169-186 (IF: 7.261)

Araújo F, Shrestha N, Shahbazi M-A, Fonte P, Mäkilä E, Salonen J, Hirvonen J, Granja PL, Santos HA, Sarmento B. The impact of nanoparticles on the mucosal translocation and transport of GLP-1 across the intestinal epithelium. Biomaterials 2014;35:9199-207. (IF: 8.312)

Bidarra SJ, Barrias CC, Fonseca KB, Barbosa MA, Soares R, Granja PL. Evaluation of injectable in situ crosslinkable alginate matrix for endothelial cells delivery. Biomaterials 2011;32:7897-904. (IF: 7.404)

Bidarra SJ, Barrias CC, Barbosa MA, Soares R, Granja PL. Immobilization of human mesenchymal stem cells within RGD-grafted alginate microspheres and assessment of their angiogenic potential. Biomacromolecules 2010;11:1956-64. (IF: 5.325)

Grellier M, Granja PL, Fricain J-C, Bidarra SJ, Renard M, Bareille R, Bourget C, Amédée J, Barbosa MA. The Effect of the Co-Immobilization of Human Osteoprogenitors and Endothelial Cells within Alginate Microspheres on Mineralization in a Bone Defect. Biomaterials 2009;30:3271-8. (IF: 7.365)

Barrias CC, Martins MCL, Almeida-Porada G, Barbosa MA, Granja PL. The correlation between the adsorption of adhesive proteins and cell behaviour on hydroxyl-methyl mixed self-assembled monolayers. Biomaterials 2009;30:307-316. (IF: 7.365)

Group Leader
Pedro Granja
pgranja@i3s.up.pt
People

Junior Researcher
Aureliana Filipa Sousa

Junior Researcher
Tiago dos Santos

Post-Doc Researcher
Rúben Pereira

PhD student
Bianca Lourenço

PhD student
Daniel Ferreira

MSc student
Eduardo Capitão

MSc student
Filipa Serôdio

MSc student
Rafaela Presa

Research Fellowship (MSc)
Manuel João Barros

Visiting Researcher
Ana Rita Fernandes

Visiting Researcher
Sara Silva

Collaborator
Ana Rita da Costa Pinto

Collaborator
Cassilda Cunha Reis

Collaborator
Ricardo Serôdio


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