ADVANCED THERAPEUTICS

We aim to develop biocompatible polymer formulations structured in nanoparticles and hydrogels that can be used as advanced vehicles for therapeutics in stroke and neurodegeneration (Alzheimer's and Parkinson diseases). Our goal is to overcome actual limitations of classic systems of drug and stem cell-based delivery that until now have translated into poor clinical outcomes.

 

We also aim to develop strategies of stem cell-based therapeutics, focused in the use of intrinsic (stem cells) and extrinsic (microenvironment) preconditioning, as well as the optimization of new mobilization/homing paradigms, to stimulate host stem cell potential.

Our laboratory is seeking to develop a drug-release system based on silk fibroin. We have tested the biocompatibility of silk fibroin within the Central Nervous System (CNS), thus demonstrating the suitability of this biomaterial for our purpose. We are able to generate different formats with silk fibroin: hydrogels, films, nanoparticles, etc. We have shown the therapeutic possibilities of the encapsulation of stem cells inside hydrogels in stroke treatment. The basis of this therapeutic approach are the creation of a microenvironment that will protect the cells from an hostile environment, as it is the damage brain, while they act as growth factor factories. We also aim to prove the feasibility of delivering different drugs and biomolecules, alone or in combination, from silk fibroin formats to the damaged CNS.

 

Main routes to target the stroke brain with biomaterial-based nanoparticles and hydrogels. González-Nieto et al. 2020. Biomaterials to Neuroprotect the Stroke Brain: A Large Opportunity for Narrow Time Windows. doi: 10.3390/cells9051074.

Advanced therapeutics images-SF deposits

Hisological identification of silk fibroin deposits over time after intracerebral injection. These results were obtained in collaboration with Biomaterials and Regenerative Engineering laboratory from the Centre for Biomedical Technology. Fernández-García et al. 2016. Safety and tolerability of silk fibroin hydrogels implanted into the mouse brain. doi: 10.1016/j.actbio.2016.09.003.

Hydrogel-based therapeutics sustains drug delivery and support cell survival and engraftment after implantation. Fernández-Serra et al. 2020. Hydrogels for neuroprotection and functional rewiring: a new era for brain engineering. doi: 10.4103/1673-5374.268891.

Representative images and quantification of mSCs expressing the EGF protein (EGFP) implanted into the striatum of non-EGFP-expressing mice over time. These results were obtained in collaboration with Biomaterials and Regenerative Engineering laboratory from the Centre for Biomedical Technology. Fernández-García et al. 2018. Cortical Reshaping and Functional Recovery Induced by Silk Fibroin Hydrogels-Encapsulated Stem Cells Implanted in Stroke Animals. doi: 10.3389/fncel.2018.00296..

(A) Viability of mesenchymal stem cells encapsulated in silk fibroin hydrogels and stiffness properties of silk fibroin hydrogels. (B) Images of coronal brain sections showing the location of mesenchymal stem cell populations encapsulated into 2% silk fibroin hydrogels after implantation into the striatum of non-EGFP (left panel) and EGFP expressing mice (right panel). These results were obtained in collaboration with Biomaterials and Regenerative Engineering laboratory from the Centre for Biomedical Technology. Fernández-Serra et al. 2020. Hydrogels for neuroprotection and functional rewiring: a new era for brain engineering. doi: 10.4103/1673-5374.268891.