Proyectos de Investigación

research

The group works mainly in the following fields of research:

 

- Advanced bioceramics for bone tissue regeneration and scaffolding. 

 

Bone pathologies are one of the most important challenges from the health, social and economical point of view. Many efforts are addressed to design materials for bone regenerative therapies instead of bone substitution with permanent and nonresorbable implants. This research line tackles the design and development of macroporous scaffolds, which supply responses adapted to the different stages of bone regeneration (cell adhesion, differentiation, proliferation, angiogenesis, etc.). For this purpose, our research team prepares implants through the control of the chemical composition, mesoporosity, macroarchitecture and functionalization of surfaces with growth factors. The synergic effect of these factors is expected to improve the regeneration processes in large bone defects.

 

- Stimuli-responsive mesoporous nanoparticles for antitumoral therapy

 

Bone cancer

Bone metastases are present in the 70% of patients who die because of cancer. Despite of the large bibliography dealing with nanovehicles as antitumoral carriers, the application of these systems in the field of bone tumors is still in the beginnings. The aim of this research line is developing stimuli-responsive nanosystems based on mesoporous silica nanoparticles. Our nanovehicles are specifically functionalized with chemical agents to target bone malignant cell. Through the surface functionalization with biphosphonates, tetracyclines, or polymalonic acid, which exhibit affinity for the bone hydroxyapatite, we explore the possibility of accumulate our nanovehicles in bone and, subsequently, release the antitumoral drugs kept inside the pores.

Neuroblastoma

Neuroblastoma (N.B.) is the most common extracranial solid cancer in childhood and the most common cancer in infancy. Nearly half of neuroblastoma cases are diagnosed when the disease has already spread through the body. In collaboration with the Hospital Infantil Universitario Niño Jesús de Madrid, we are developing a research line to treat this cancer with mesoporous nanoparticles. These systems are loaded with cytotoxic drugs, immunomodulators and/or plasmids. Their surfaces exhibit molecules (folic acid, biotine, etc.), proteins or antibodies (transferrine, antGD2) that selectively recognize malignant cells. Once located in the cancer area, the nanosystems trigger the cargo by means of stimuli-responsive mechanisms 

 

- Design of biomaterials and surfaces with antibacterial properties

Bone Infection

Chronic infections constitute one of the greatest challenges in orthopaedic surgery in the world's healthcare systems. Difficulties derive mainly from the biofilm-mode of living of bacteria with resistances against immunological defence and conventional antibiotics. All this has serious repercussions for patients with high percent of mobility and excessive health costs. The aim of this research line is to develop new biomaterials and surfaces capable of preventing bacterial adhesion, killing bacteria and destroying the biofilm. In this context, Vallet-Regí’s research group is exploring three main approaches:

(1) Design of implant surfaces that inhibit the bacterial adhesion through the creation of low fouling biomaterial surfaces.

 

 

(2) Design multifunctional scaffolds with both antimicrobial and bone regenerative properties

 

(3) Design of nanocarriers based on Mesoporous Silica Nanoparticles (MSN) with bacteria and biofilm targeting capability, which notably enhances the antimicrobial power of the loaded antibiotics, as well as ions with therapeutic antibacterial activity.

 

Journals Covers

 

         
   
       
         
         
           
           
           

Selected references

M. Vallet-Regí, D. Lozano, B. González, I. Izquierdo. BIOMATERIALS AGAINST BONE INFECTION. Adv. Healthcare Mater. 2000310 (2020).

M. Manzano, M. Vallet-Regí. MESOPOROUS SILICA NANOPARTICLES FOR DRUG DELIVERY. Adv. Funct. Mater. 30, 1902634 (2020)

M. Martínez, I. Izquierdo, M. Colilla, M. Vallet-Regí. CONCANAVALIN A-TARGETED MESOPOROUS SILICA NANOPARTICLES FOR INFECTION TREATMENT. Acta Biomaterialia. 96, 547-556 (2019).

P. Mora, D. Lozano, M. Manzano, M. Vallet-Regí. NANOPARTICLES TO KNOCKDOWN OSTEOPOROSIS-RELATED GENE AND PROMOTE OSTEOGENIC MARKERS EXPRESSION FOR OSTEOPOROSIS TREATMENT. ACS Nano. 13, 5451-5464 (2019).

 S. Montalvo, G. Aragoneses, L. Garcia, M. Vallet Regí, María, B. González, J.L. Luque. CANCER CELL TARGETING AND THERAPEUTIC DELIVERY OF SILVER NANOPARTICLES BY TRANSFERRIN DECORATED MESOPOROUS SILICA NANOCARRIERS: INSIGHTS INTO THE ACTION MECHANISMS BY QUANTITATIVE PROTEOMICS.  Nanoscale. 11, 4531-4545 (2019).

G. Villaverde, A. Alfranca, A. Gonzalez, G.J. Melen, R. Castillo, M. Ramirez, A. Baeza, M. Vallet-Regi. MOLECULAR SCAFFOLDS AS DOUBLE TARGETING AGENTS FOR THE DIAGNOSIS AND TREATMENT OF NEUROBLASTOMA. Angew. Chem. Int. Ed. 58, 3067-3072 (2019).

M. Manzano, M. Vallet-Regí. ULTRASOUND RESPONSIVE MESOPOROUS SILICA NANOPARTICLES FOR BIOMEDICAL APPLICATIONS. Chem. Commun. 55, 2731-2740 (2019).

R. Castillo, D. Lozano, M. Vallet-Regí. BUILDING BLOCK BASED CONSTRUCTION OF MEMBRANE-ORGANELLE DOUBLE TARGETED NANOSYSTEM FOR TWO-DRUG DELIVERY. Bioconjug. Chem. 29 (11), 3677-3685  (2018).

B. González, M. Colilla, J. Díez, D. Pedraza, M. Guembe, I. Izquierdo-Barba, M. Vallet-Regí. MESOPOROUS SILICA NANOPARTICLES DECORATED WITH POLYCATIONIC DENDRIMERS FOR INFECTION TREATMENT. Acta Biomaterialia. 68, 261-271  (2018).

J.L Paris, M. Manzano, M.V. Cabañas, M. Vallet-Regi. MESOPOROUS SILICA NANOPARTICLES ENGINEERED FOR ULTRASOUND-INDUCED UPTAKE BY CANCER CELLS. Nanoscale. 10, 6402-6408 (2018).

M. Martínez, D. Lozano, M. Colilla, M. Vallet-Regí. LECTIN-CONJUGATED PH-RESPONSIVE MESOPOROUS SILICA NANOPARTICLES FOR TARGETED BONE CANCER TREATMENT. Acta Biomaterialia. 65, 393-404 (2018).

M.R. Villegas, A. Baeza, A. Noureddine, P. Durfee, K. Butler, J. Agola, J.C. Brinker, M. Vallet Regí. MULTIFUNCTIONAL PROTOCELLS FOR ENHANCED PENETRATION IN 3D EXTRACELLULAR TUMORAL MATRICES. Chem. Mater. 30, 112−120 (2018). 

A.Y. Rwei, J.L. Paris, B. Wang, W. Wang, C.D. Axon, M. Vallet-Regí, R. Langer, D,S. Kohane. ULTRASOUND TRIGGERED LOCAL ANAESTHESIA. Nat. Biomed. Eng.  1 (8), 644–653 (2017).

J.L. Paris, P. de la Torre, M.V. Cabañas, M. Manzano, M. Grau, A.I. Flores, M. Vallet-Regí. VECTORIZATION OF ULTRASOUND-RESPONSIVE NANOPARTICLES IN PLACENTAL MESENCHYMAL STEM CELLS FOR CANCER THERAPY. Nanoscale, 9, 5528–5537 (2017).

G. Villaverde, V. Nairi, A. Baeza, M. Vallet-Regi. DOUBLE SEQUENTIAL ENCRYPTED TARGETING SEQUENCE: A NEW CONCEPT FOR BONE CANCER TREATMENT. Chem. Eur. J. 23,7174 –7179 (2017).

R Cortés-Gil, L. Ruiz-González, D. González-Merchante, J.M. Alonso, A. Hernando, S. Trasobares, M. Vallet-Regí, J.M. Rojo and J. M. González-Calbet. EXPERIMENTAL EVIDENCE OF THE ORIGIN OF PHASE SEPARATION IN LOW HOLE-DOPED COLOSSAL MAGNETORESISTANT MANGANITES. Nano Letters. 16, 760−765 (2016).

J.L. Paris, M. Cabañas, M. Manzano, M. Vallet-Regí. POLYMER-GRAFTED MESOPOROUS SILICA NANOPARTICLES AS ULTRASOUND-RESPONSIVE DRUG CARRIERS. ACS Nano. 9 (11) 11023-11033  (2015).

M.R. Villegas, A.Baeza, M. Vallet Regí. HYBRID COLLAGENASE NANOCAPSULES FOR ENHANCED NANOCARRIER PENETRATION IN TUMORAL TISSUES. ACS Appl. Mater. Inter. 7, 24075-24081 (2015).

N. Mas, D. Arcos, E. Aznar, S. Sánchez, F. Sancenón, A. García, M. D. Marcos, A. Baeza, M. Vallet-Regí, and R. Martínez. TOWARDS THE DEVELOPMENT OF SMART 3D “GATED SCAFFOLDS” FOR ON-COMMAND DELIVERY. Small. 10 (23), 4859-4864 (2014).

A. Baeza, E. Guisasola, A. Torres-Pardo, J.M. González-Calbet, G.J. Melen, M. Ramirez, M. Vallet-Regí. HYBRID ENZYME-POLYMERIC CAPSULES/MESOPOROUS SILICA NANODEVICE FOR IN SITU CYTOTOXIC AGENT GENERATION. Adv. Funct. Mater. 24 (29), 4625-4633 (2014).

D. Arcos,  A.R. Boccaccini,  M. Bohner, A. Díez-Pérez, M. Epple, E. Gómez-Barrena, A. Herrera, J.A. Planell, L. Rodríguez-Mañas, M. Vallet-Regí. THE RELEVANCE OF BIOMATERIALS TO THE PREVENTION AND TREATMENT OF OSTEOPOROSIS. Acta Biomaterialia. 1793–1805 (2014).

M.C.Matesanz, M.Vila, M.J.Feito, J.Linares, G.Gonçalves, M.Vallet-Regi, P.A.A.P.Marques, M.T.Portolés. THE EFFECTS OF GRAPHENE OXIDE NANOSHEETS LOCALIZED ON F-ACTIN FILAMENTS ON CELL-CYCLE ALTERATIONS. Biomaterials. 34, 1562-1569 (2013).

D. Arcos, M. Vallet-Regí. BIOCERAMICS FOR DRUG DELIVERY. Acta Materialia. 61, 890-911 (2013).

J. Simchenn, A. Baeza, D. Ruiz, M. Esplandiu, M. Vallet-Regí. ASYMMETRIC HYBRID SILICA NANOMOTORS FOR CAPTURE AND CARGO TRANSPORT: TOWARDS A NOVEL MOTION-BASED DNA SENSOR. Small. 8(13), 2053-2059 (2012)

A. Baeza, E. Guisasola, E. Ruiz-Hernández and M. Vallet-Regí. MAGNETICALLY TRIGGERED MULTI-DRUG RELEASE BY HYBRID MESOPOROUS SILICA NANOPARTICLES. Chem. Mater. 24, 517-524 (2012)

M. Vallet-Regí, M. Colilla and B. González. MEDICAL APPLICATIONS OF ORGANIC-INORGANIC HYBRID MATERIALS WITHIN THE FIELD OF SILICA-BASED BIOCERAMICS. Chem. Soc. Rev. 70, 596-607 (2011)

M Vallet-Regí and E. Ruiz-Hernández. BIOCERAMICS: FROM BONE REGENERATION TO CANCER NANOMEDICINE. Adv. Mater. 23, 5177–5218. (2011) Review.

E. Ruiz-Hernández, A. Baeza, M. Vallet-Regí. SMART DRUG DELIVERY THROUGH DNA/MAGNETIC NANOPARTICLE GATES. ACS Nano. 5 (2), 1259–1266 (2011)

M. Vallet-Regí, M. Manzano, J.M. González-Calbet and E. Okunishid. EVIDENCE OF DRUGS CONFINEMENT INTO SILICA MESOPOROUS MATRICES BY STEM CS CORRECTED MICROSCOPY. Chem. Commun. 46, 46, 2956 - 2958 (2010)

M. Vallet-Regi. NANOSTRUCTURED MESOPOROUS SILICA MATRICES IN NANOMEDICINE. J. Internal Medicine. 267, 22-43 (2010)

M. Vallet-Regí, F. Balas, D. Arcos. MESOPOROUS MATERIALS FOR DRUG DELIVERY. Angew. Chem. Int. Ed. 46, 7548-7558 (2007) Review.

Vallet-Regí ORDERED MESOPOROUS MATERIALS IN THE CONTEXT OFDRUG DELIVERY SYSTEMS AND TISSUE ENGINEERING. Chem. Eur. J. 12, 5934-5943 (2006) Review.

M. Vallet-Regí. REVISITING CERAMICS FOR MEDICAL APPLICATIONS. J. Chem. Soc. Dalton Trans. 5211–5220 (2006)

M. Vallet-Regí and J. González-Calbet. CALCIUM PHOSPHATES AS SUBSTITUTION OF BONE TISSUES. Prog. Solid State Ch. 32, 1-31 (2004) Review.

M. Vallet-Regí. CERAMICS FOR MEDICAL APPLICATIONS. Perspective Article. J. Chem. Soc. Dalton Trans. 97-108. (2001) Review.

M. Vallet-Regi, A Ramila, R. P. del Real, J. Perez-Pariente. A NEW PROPERTY OF MCM-41: DRUG DELIVERY SYSTEM. Chem. Mater. 13, 308-311. (2001).