Where Ideas grow
Biomaterials for Multistage Drug & 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.

Human mesenchymal stem cells cultured under 3D conditions within soft RGD-alginate hydrogels. Cells rapidly modify their local mechanical/biochemical environment, becoming embedded within an endogenous fibronectin-rich ECM (Green: F-actin filaments, Red: Fibronectin mesh).
Selected Publications
A single-component hydrogel bioink for bioprinting of bioengineered 3D constructs for dermal tissue engineering. Materials Horizons5(6):1100-1111, 2018. [Journal: Article] [CI: 3] [IF: 13,2 (*)]
DOI: 10.1039/c8mh00525g SCOPUS: 85055847804

Gravity, Tissue Engineering, and the Missing Link. Trends in Biotechnology36(4):343-347, 2018. [Journal: Short Survey] [CI: 1] [IF: 13,6 (*)]
DOI: 10.1016/j.tibtech.2017.10.017 SCOPUS: 85034606920

Cell-instructive pectin hydrogels crosslinked via thiol-norbornene photo-click chemistry for skin tissue engineering. Acta Biomaterialia66:282-293, 2018. [Journal: Article] [CI: 17] [IF: 6,4 (*)]
DOI: 10.1016/j.actbio.2017.11.016 SCOPUS: 85034850058

Novel sintering-free scaffolds obtained by additive manufacturing for concurrent bone regeneration and drug delivery: Proof of concept. Materials Science and Engineering C94:426-436, 2019. [Journal: Article] [CI: 2] [IF: 5,1 (*)]
DOI: 10.1016/j.msec.2018.09.050 SCOPUS: 85053772854

Engineering proteolytically-degradable artificial extracellular matrices. Progress in Polymer Science39(12):2010-2029, 2014. [Journal: Review] [CI: 27] [IF: 26,9]
DOI: 10.1016/j.progpolymsci.2014.07.003 SCOPUS: 84910642434

Biomechanical performance of hybrid electrospun structures for skin regeneration. Materials Science and Engineering C93:816-827, 2018. [Journal: Article] [CI: 2] [IF: 5,1 (*)]
DOI: 10.1016/j.msec.2018.08.050 SCOPUS: 85054091151

Decellularized human colorectal cancer matrices polarize macrophages towards an anti-inflammatory phenotype promoting cancer cell invasion via CCL18. Biomaterials124:211-224, 2017. [Journal: Article] [CI: 17] [IF: 8,8]
DOI: 10.1016/j.biomaterials.2017.02.004 SCOPUS: 85013069713

Nutlin-3a and Cytokine Co-loaded Spermine-Modified Acetalated Dextran Nanoparticles for Cancer Chemo-Immunotherapy. Advanced Functional Materials27(42):, 2017. [Journal: Article] [CI: 10] [IF: 13,3]
DOI: 10.1002/adfm.201703303 SCOPUS: 85028762962

CD44 alternative splicing in gastric cancer cells is regulated by culture dimensionality and matrix stiffness. Biomaterials98:152-162, 2016. [Journal: Article] [CI: 11] [IF: 8,4]
DOI: 10.1016/j.biomaterials.2016.04.016 SCOPUS: 84966708392

Functionalized materials for multistage platforms in the oral delivery of biopharmaceuticals. Progress in Materials Science89:306-344, 2017. [Journal: Review] [CI: 10] [IF: 23,8]
DOI: 10.1016/j.pmatsci.2017.05.001 SCOPUS: 85020029869

Advances in electrospun skin substitutes. Progress in Materials Science84:314-334, 2016. [Journal: Review] [CI: 23] [IF: 31,1]
DOI: 10.1016/j.pmatsci.2016.09.006 SCOPUS: 84992128552

Additive manufactured polymeric 3D scaffolds with tailored surface topography influence mesenchymal stromal cells activity. Biofabrication8(2):, 2016. [Journal: Article] [CI: 15] [IF: 5,2]
DOI: 10.1088/1758-5090/8/2/025012 SCOPUS: 84987677248

Biofunctionalized pectin hydrogels as 3D cellular microenvironments. Journal of Materials Chemistry B3(10):2096-2108, 2015. [Journal: Article] [CI: 28] [IF: 4,9]
DOI: 10.1039/c4tb00885e SCOPUS: 84923913719

Injectable MMP-sensitive alginate hydrogels as hMSC delivery systems. Biomacromolecules15(1):380-390, 2014. [Journal: Article] [CI: 47] [IF: 5,8]
DOI: 10.1021/bm4016495 SCOPUS: 84892606344

Pectin-based injectable biomaterials for bone tissue engineering. Biomacromolecules12(3):568-577, 2011. [Journal: Article] [CI: 103] [IF: 5,5]
DOI: 10.1021/bm101110x SCOPUS: 79955409005