Group Leader/s

 

intro

The “Cell-Biomaterial Recognition Lab” explores the interactions between cells and biomaterials with applications for bone tissue repair. Biomaterials under study comprise metallic materials, as are cobalt-chromium alloys with high carbon content and biodegradable magnesium-base materials, and ceramic materials as are the hydroxyapatites.

Different cellular and molecular approaches and tools are carried out to understand the biological response that takes place as a consequence of the interaction with the material with the final goal to select materials biocompatibles with minimal adverse effects, being one of the most relevant complications the osteolysis produced by metallic particles and ions. The metallic material degradation (particles and ions) produces as a final consequence the loosening of the implanted prostheses that suppose an inconvenient for patients with an economical cost that affect the sustainability of the public health system.   

Our biological studies on surface-modified cobalt-chromium alloys with high carbon content, with a new strategy to minimize wear process ameliorating lubrication, and magnesium-based materials with a biodegradation kinetic rate synchronized with bone tissue regeneration and functionalized hydroxyapatites with different proteins that enhances activities of other peptides involved in bone tissue growth, will allow to get better implants for bone tissue repair.

 

 

Cryosem images of 3D osteoblasts MC3T3-E1 cell cultures in CellCeram scaffolds. Panel A: scaffold in the absence of cells and particles used as control for 3D osteoblasts cell cultures (scale bar: 1 mm); Panel B: scaffold incubated with CoCr particles. Particles with round shape appear inside scaffold labeled with a black arrow (scale bar: 20 μm); Panel C: osteoblasts MC3T3-E1 cells cultured on scaffolds in presence of 0.5 mg/ml of CoCr particles (scale bar: 50 μm). Extended cells´filopodia are observed on scaffold surface; Panel D: detail of osteoblasts cell cultured on scaffold in presence of 0.5 mg/ml of CoCr particles (scale bar: 20 μm)
Cryosem images of 3D osteoblasts MC3T3-E1 cell cultures in CellCeram scaffolds. Panel A: scaffold in the absence of cells and particles used as control for 3D osteoblasts cell cultures (scale bar: 1 mm); Panel B: scaffold incubated with CoCr particles. Particles with round shape appear inside scaffold labeled with a black arrow (scale bar: 20 mm); Panel C: osteoblasts MC3T3-E1 cells cultured on scaffolds in presence of 0.5 mg/ml of CoCr particles (scale bar: 50 mm). Extended cells´ filopodia are observed on scaffold surface; Panel D: detail of osteoblasts cell cultured on scaffold in presence of 0.5 mg/ml of CoCr particles (scale bar: 20 mm).
 

BT Pérez-Maceda, ME López-Fernández, I. Díaz, A. Kavanaugh, F. Billi, ML Escudero, MC García-Alonso, RM Lozano  [2017]. Osteoblasts MC3T3-E1 Response in 2D and 3D Cell Cultures Models to High Carbon Content CoCr Alloy Particles. Effect of Metallic Particles on Vimentin Expression. J. Mat. Sci. Res. 6: 41-55.

Alvarez F., Lozano Puerto R.M., Pérez-Maceda B., Grillo C.A., and Fernández Lorenzo de Mele M.  [2016]. Time-Lapse Evaluation of Interactions Between Biodegradable Mg Particles and Cells. Microsc. Microanal. 22, 1–12.

Bodelón O.G., Iglesias C., Díaz I., Clemente C., Pérez-Maceda B.T., Lozano R.M., Hernández L.S., García-Alonso M.C. and Escudero M.L.  [2015]. Biomateriales metálicos biodegradables en la reducción de fracturas. Acta Científica y Tecnológica. 25, 15-21

Alvarez F, Lozano Puerto RM, Pérez-Maceda BT, Grillo CA, Fernández Lorenzo MA.  [2014]. Multidimensional microscopy: A suitable technique to follow in vivo the interaction between biodegradable biomaterials and cells. In “Microscopy: advances in scientific research and education”. Microscopy book nº 6 Vol.1. 523-529

Alvarez F, Lozano Puerto R, Pérez-Maceda B, Grillo C, Schilardi P, Fernández Lorenzo M  [2013]. Efecto de micropartículas de Mg con y sin tratamiento con KF en células osteoblásticas y macrofagos. The Journal of the Argentine Chemical Society. 100: 48-52

Lozano RM*, Pérez-Maceda BT, Carboneras M, Onofre-Bustamante E, García-Alonso MC, Escudero ML  [2013]. Response of MC3T3-E1 osteoblasts, L929 fibroblasts and J774 macrophages to fluoride surface-modified AZ31 magnesium alloy. Journal of Biomedical Materials Research: Part A. 101: 2753-2762.

Lozano, D., Feito, M.J., Portal-Nuñez, S., Lozano, R.M., Matesanz, M.C., Serrano, M.C., Vellet-Regí, M., Portolés, M.T. and Esbrit, P.  [2012]. Osteostatin improves the osteogenic activity of fibroblast growth factor-2 immobilized in Si-doped hydroxyapatite in osteoblastic cells. Acta Biomater. 8, 2770-2777.

Matesanz, M.C., Feito, M-J., Ramírez-Santillán, C., Lozano, R.M., Sánchez-Salcedo, S., Arcos, D., Vallet-Regí, M. and Portolés, M.T.  [2012]. Signaling pathways of immobilized FGF-2 on silicon substituted hydroxyapatite. Macromol Biosci. 12(4):446-453. doi: 10.1002/mabi.201100456. Epub 2012 Mar 2.

Carboneras, M., Iglesias, C., Pérez-Maceda, B.T., del Valle, J.A., García-Alonso, M.C., Alobera, M.A., Clemente, C., Rubio, J.C., Escudero, M.L. and Lozano, R.M.  [2011]. Corrosion behaviour and in vitro/in vivo biocompatibility of surface-modified AZ31 alloy. Rev. Metal. 47, 212-223.

Carboneras, M., Pérez-Maceda, B-T, del Valle, J.A., García-Alonso, M.C., Lozano, R.M. and Escudero, M.L.  [2011]. In vitro performance of magnesium processed by different routes for bone regeneration applications. Materials Letters 65, 3020-3023.

 

Funding

Biocompatibility and inflammatory reponse involve in periprosthesic osteolysis of new metallic materials with graphitic solid lubricants. Reference: MAT2015-67750-C3-2-R. (2016-2018). Funding agency: Ministerio de Economía y Competitividad. IP: Rosa Mª Lozano Puerto y Blanca T. Pérez Maceda

Cell biocompatibility of metallic wears debris derived from the synergic process of wear and corrosion of the pair metal on metal of a CoCr alloy. Reference: MAT2011-29152-C02-02. Funding agency:  Ministerio de Ciencia e Innovación. (2012-2014). IP: Rosa Mª Lozano Puerto

Bioceramic scaffolds for tissue engineering. Reference: CAM  S2009/MAT1472. (2010-2014). Funding agency: Comunidad de Madrid. IP: María Vallet Regí. Rosa Mª Lozano participates as associated member to Dra. María Teresa Portolés Pérez lab. at the Universidad Complutense Madrid.

In vitro and in vivo studies of the interaction of cell and new surfaces of magnesium-based metallic biomaterials. Reference: MAT2008-06719-C03-02/MAT. (2009-2011). Funding agency: Ministerio de Ciencia e Innovación. IP: Rosa Mª Lozano Puerto

 

 

More info

Patents:

Buchanan, B. B., Lozano, R. M., Yee, B. C., Kobrehel, K., Frick, O. L. y Ermel, R. W.Neutralization of food allergens by thioredoxin. WO9612799 (2/5/1996); US5792506 (11/8/1998); US6190723 (20/2/2001)

Buchanan, B. B., del Val, G., Lozano, R. M., Jiao, J., Wong, J.H. and Yee, B.C. Increasing the digestibility of food proteins by thioredoxin reduction.WO9920122 (29/4/1999); US5952034 (14/9/1999); US6838113 (4/1/2005)

Buchanan, B.B., del Val, G., Lozano, R.M., Wong, J.H., Yee, B.C and Frick, O.L. Alleviation of the allergenic potential of airborne and contact allergens by thioredoxin. WO0044781 (3/8/2000); US7,074,900 (11/07/2006)

Buchanan, B.B., Yee, B.C, Kobrehel, K., Lozano, R.M, Wong, J.H., Jiao, J and Sungho, S. Use of thiol redox proteins for reducing protein intramolecular disulfide bonds, for improving the quality of cereal products, dough and baked goods and for inactivating snake, bee and scorpion toxins.US6113951 (5/9/2000); US6114504 (5/9/2000); US6600021 (29/7/2003); US2003215542 (20/11/2003); EPO0863154 (9/9/1998)

Giménez Gallego, G., Valverde López, S, Lozano Puerto, R.M. and Cuevas, P. Pharmaceutical compositions containing sulphonic acid derivatives. WO2004078704. Nº Patente OEPM: 2214968 (26/10/2005). Transferida al laboratorio farmacéutico ITALFARMACO S.A.

Cuevas Sánchez , P., Romero Garrido, A., Giménez-Gallego, G. Valverde López, S. and Lozano Puerto, R.M. Methods of use for 2,5-dihydroxybenzene sulfonic acid compounds for the treatment of cancer, rosacea and psoriasis. WO2005/077352. US patent application: 11/506,489 (16/08/2006). Transferida a ACTION MEDICINES, S.L.

Cuevas Sánchez , P., Giménez-Gallego, G., Sáenz de Tejada Gorman, I., Angulo Frutos, J., Valverde López, S., Romero Garrido, A. and Lozano Puerto, R.M. Use of 2,5-dihydroxybenzene derivatives for treating actinic keratosis. WO2008/020025 (21-02-2008) PCT/EP2007/058438. Transferida a ACTION MEDICINES, S.L.

Cuevas Sánchez , P., Giménez-Gallego, G., Sáenz de Tejada Gorman, I., Angulo Frutos, J., Valverde López, S., Romero Garrido, A. and Lozano Puerto, R.M. 2,5-dihydroxybenzene derivatives for the treatment dermatitis. WO2008/020026 (21-02-2008 )PCT/EP2007/058439. Transferida a ACTION MEDICINES, S.L.

Cuevas Sánchez , P., Giménez-Gallego, G., Sáenz de Tejada Gorman I., Angulo Frutos, J., Valverde López, S., Romero Garrido, A. and Lozano Puerto, R.M. 2,5-dihydroxybenzene compounds for the treatment of rosacea. WO2008/020028 (21-02-2008) PCT/EP2007/058441. Transferida a ACTION MEDICINES, S.L.

Cuevas Sánchez , P., Giménez-Gallego, G., Sáenz de Tejada Gorman I., Angulo Frutos, J., Valverde López, S., Romero Garrido, A. and Lozano Puerto, R.M. 2,5-dihydroxybenzene compounds for the treatment of psoriasis.WO2008/020030 (21-02-2008) PCT/EP2007/058443. Transferida a ACTION MEDICINES, S.L.

Cuevas Sánchez , P., Giménez-Gallego, G., Sáenz de Tejada Gorman, I., Angulo Frutos, J., Lozano Puerto, R.M, Romero Garrido, A and Valverde López, S. Use of 2,5-dihydroxybenzene derivatives for the treatment of angiogenic diseases. WO2008/020031 (21-02-2008) PCT/EP2007/058444. Transferida a ACTION MEDICINES, S.L.

Cuevas Sánchez , P., Giménez-Gallego, G., Sáenz de Tejada Gorman, I., Angulo Frutos, J., Lozano Puerto, R.M, Romero Garrido, A and Valverde López, S. Use of 2,5-dihydroxybenzene derivatives for the treatment of ocular diseases. WO2008/020032 (21-02-2008) PCT/EP2007/058445. Transferida a ACTION MEDICINES, S.L.

Cuevas Sánchez , P., Giménez-Gallego, G., Sáenz de Tejada Gorman, I., Angulo Frutos, J., Lozano Puerto, R.M, Romero Garrido, A and Valverde López, S. Use of 2,5-dihydroxybenzene sulfonic acid derivatives for the treatment of arthritis and pain. WO2008/020033 (21-02-2008) PCT/EP2007/058446. Transferida a ACTION MEDICINES, S.L.

Cuevas Sánchez , P., Giménez-Gallego, G., Sáenz de Tejada Gorman, I., Angulo Frutos, J., Lozano Puerto, R.M, Romero Garrido, A and Valverde López, S. Use of 2,5-dihydroxybenzene sulfonic acid compounds for treatment of hemangiomas or hemangioblastomas. WO2008/020034 (21-02-2008) PCT/EP2007/058447. Transferida a ACTION MEDICINES, S.L.

Cuevas Sánchez , P., Giménez-Gallego, G., Sáenz de Tejada Gorman, I., Angulo Frutos, J., Lozano Puerto, R.M, Romero Garrido, A., Valverde López, S. and García Gómez, I. Use of 2,5-dihydroxybenzene sulfonic acid compounds for treating obesity, hirsutism, hypertricosis and viral warts. WO2008/020037(21-02-2008)PCT/EP2007/058451.Transferida a ACTION MEDICINES, S.L.

Cuevas Sánchez , P., Giménez-Gallego, G., Sáenz de Tejada Gorman, I., Angulo Frutos, J., Lozano Puerto, R.M, Romero Garrido, A and Valverde López, S. 2,5-dihydroxybenzene sulfonic acid compounds for treating cancers and hematological dyscrasias.WO2008/020039(21-02-2008)PCT/EP2007/058453. Transferida a ACTION MEDICINES, S.L.

Cuevas Sánchez , P., Giménez-Gallego, G., Sáenz de Tejada Gorman, I., Angulo Frutos, J., Lozano Puerto, R.M, Romero Garrido, A and Valverde López, S. 2,5-dihydroxybenzene sulfonic acid derivatives for the treatment of fibrosis. WO2008/020040(21-02-2008)PCT/EP2007/058454.Transferida a ACTION MEDICINES, S.L.

Cuevas Sánchez , P., Giménez-Gallego, G., Sáenz de Tejada Gorman I., Angulo Frutos, J., Valverde López, S., Romero Garrido, A. and Lozano Puerto, R.M. 2,5-dihydroxybenzene compounds for the treatment of skin cancer. Patent Number: 8101660. 24 Enero 2012. WO patent application: 2008/020027 Pub. Date:21-02-2008 PCT/EP2007/058440. Transferida a Amderma Pharmaceuticals LLC (Bridgewater, NJ, USA) Antes ACTION MEDICINES, S.L.

Cuevas Sánchez , P., Giménez-Gallego, G., Sáenz de Tejada Gorman, I., Angulo Frutos, J.,Moreno Nuncio, F.J., Rivas López, L.I. Fernández Jaen, T.F., Lozano Puerto, R.M, Romero Garrido, A and Valverde López, S. Use of 2,5-dihydroxybenzene sulfonic acid derivatives for tissue reactive diseases. Patent Number: EP2056805 B1. Fecha patente: 25/5/2011. WO patent application: 2008/020042.Pub.Date:21-02-2008 PCT/EP2007/058456. Transferida a Amderma Pharmaceuticals LLC (Bridgewater, NJ, USA) Antes ACTION MEDICINES, S.L.