DEVELOPMENT OF NEW BIOMATERIALS AND ASSOCIATED SYSTEMS FOR CARDIAC FUNCTION RECOVERY IN INFARCTION TISSUE (Q3135073)
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Project Q3135073 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | DEVELOPMENT OF NEW BIOMATERIALS AND ASSOCIATED SYSTEMS FOR CARDIAC FUNCTION RECOVERY IN INFARCTION TISSUE |
Project Q3135073 in Spain |
Statements
108,900.0 Euro
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217,800.0 Euro
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50.0 percent
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1 January 2019
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31 December 2021
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UNIVERSIDAD DE VALLADOLID
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41°39'7.67"N, 4°43'42.82"W
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47186
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LA REGENERACION CARDIACA DESPUES DE UNA LESION (POR EJ. INFARTO DE MIOCARDIO) SE VE EXTREMADAMENTE DIFICULTADA POR LA FALTA DE CELULAS MADRE CARDIACAS RESIDENTES EN CORAZONES ADULTOS Y LA INCAPACIDAD DE PROLIFERACION DE LOS CARDIOMIOCITOS. ESTO CONDUCE A LA FORMACION DE UN MUSCULO CARDIACO CON CICATRICES, QUE ES MUCHO MAS PROBABLE QUE CAUSE INSUFICIENCIA CARDIACA Y CUYA REGENERACION HOY EN DIA NO ES POSIBLE._x000D_ LA INGENIERIA DEL TEJIDO CARDIOVASCULAR EXPLORA VIAS PARA RESTAURAR LA FUNCIONALIDAD CARDIACA Y REEMPLAZAR LOS TEJIDOS CARDIOVASCULARES ANORMALES O NECROTICOS. EXISTE CONSENSO EN LA COMUNIDAD CIENTIFICA Y MEDICA ACERCA DE LA NECESIDAD DE NUEVOS BIOMATERIALES QUE TENGAN LAS PROPIEDADES REQUERIDAS PARA ASEGURAR EL INJERTO CELULAR Y ESTIMULAR LA REGENERACION DEL TEJIDO CARDIACO. LA BUSQUEDA DE DICHOS MATERIALES CONSTITUYE UN IMPORTANTE RETO DADA LA COMPLEJIDAD ESTRUCTURAL INHERENTE DEL TEJIDO CARDIACO: EL CORAZON ES UN ORGANO COMPLEJO CON UNA VARIEDAD DE CELULAS EN EL QUE LA MATRIZ EXTRACELULAR, BASADA PRINCIPALMENTE EN FIBRAS DE COLAGENO, NO SOLO PROPORCIONA LA SEÑALIZACION BIOQUIMICA ADECUADA, SINO QUE TAMBIEN ACTUA COMO SOPORTE QUE PERMITE LAS CONEXIONES CELULARES CORRECTAS Y COMO GUIA PARA LA TRANSMISION DE LAS SEÑALES ELECTRICAS._x000D_ POR OTRO LADO, SE SABE QUE EN LOS CARDIOMIOCITOS DE LOS RECIEN NACIDOS TIENEN UN COMPORTAMIENTO PROLIFERATIVO DEL QUE CARECEN LOS DE LOS ADULTOS. UNA DE LAS DIFERENCIAS ENTRE LOS CARDIOMIOCITOS ADULTOS Y FETALES/RECIEN NACIDOS ES LA CAPACIDAD DE ESTOS ULTIMOS DE TOMAR LACTATO COMO FUENTE DE ENERGIA, LO QUE SE CORRELACIONA CON EL AMBIENTE RICO EN LACTATO QUE SE ENCUENTRA EN LA PLACENTA. ENSAYOS IN VITRO PREVIOS SUGIEREN QUE EN PRESENCIA DE LACTATO LOS CARDIOMIOCITOS MUESTRAN MAYORES TASAS DE PROLIFERACION Y CAPACIDAD PARA FORMAR UN MUSCULO CARDIACO FUNCIONAL. _x000D_ EL PRESENTE PROYECTO PROPONE EL DESARROLLO DE UNA NUEVA FAMILIA DE BIOMATERIALES AVANZADOS BASADOS RECOMBINAMEROS TIPO ELASTINA (ELRS), CAPACES DE LIBERAR LACTATAO, PARA LA BIOFABRICACION DE PARCHES CARDIACOS MEDIANTE TECNOLOGIAS DE PROCESADO AVANZADAS TALES COMO LA BIOIMPRESION 3D Y EL ELECTROHILADO. _x000D_ LOS ELRS PREVISTOS EN ESTE PROYECTO ESTAN FORMADOS POR LA REPETICION DE ALGUNOS PEPTIDOS QUE SE ENCUENTRAN EN LA ELASTINA NATURAL Y QUE PRESENTAN PROPIEDADES DIFICILMENTE ENCONTRABLES EN OTROS BIOMATERIALES, TALES COMO UNA EXCELENTE BIOCOMPATIBILIDAD, CAPACIDAD DE RESPUESTA A ESTIMULOS EXTERNOS, AUTOENSAMBLADO, PROPIEDADES MECANICAS OPTIMAS Y CUSTOMIZABLES DE SUS HIDROGELES Y POSIBLIDAD DE INCLUIR BIOACTIVIDADES ESPECIFICAS, TALES COMO SECUENCIAS DE ADHESION CELULAR Y DOMINIOS SENSIBLES A PROTEASAS QUE GARANTICEN QUE EL SCAFFOLD SE DEGRADA DE FORMA CONTROLADA A LO LARGO DEL TIEMPO SIMULTANEAMENTE A LA PROLIFERACION CELULAR Y A LA FORMACION DE MATRIZ EXTRACELULAR. ADEMAS, LOS ELRS PRESENTAN LA CAPACIDAD DE SER MODIFICADOS QUIMICAMENTE PARA PORTAR GRUPOS REACTIVOS QUE LES PERMITAN, ENTRE OTRAS COSAS, INTERACCIONAR Y RETENER LACTATO QUE POSTERIORMENTE SE LIBERARA DE MANERA SOSTENIDA COMO FUENTE DE ENERGIA DE LOS CARDIOMIOCITOS._x000D_ EN TORNO A LOS ELRS, SE PROPONEN TRES ESTRATEGIAS DE FORMACION DE SCAFFFOLDS CARDIACOS PORTADORES DE LACTATO: OBTENCION DE UN HIDROGEL INYECTABLE POR ENTRECRUZAMIENTO QUIMICO, OBTENCION DE UN PARCHE BASADO EN NANOFIBRAS ALINEADAS MEDIANTE LA TECNOLOGIA DEL ELECTROHILADO Y FABRICACION DE UN SCAFFOLD CARDIACO CON ESTRUCTURA ADECUADA MEDIANTE TECNOLOGIA DE IMPESION 3D. (Spanish)
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CARDIAC REGENERATION AFTER AN INJURY (EG, MYOCARDIAL INFARCTION) IS GREATLY COMPLICATED BY THE LACK OF CARDIAC STEM CELLS RESIDENT IN ADULT HEARTS AND THE INABILITY OF CARDIOMYOCYTES TO PROLIFERATE. THIS LEADS TO THE FORMATION OF A SCARRED HEART MUSCLE, WHICH IS MUCH MORE LIKELY TO CAUSE HEART FAILURE AND WHOSE REGENERATION IS NOT CURRENTLY POSSIBLE._x000D_ CARDIOVASCULAR TISSUE ENGINEERING EXPLORES PATHWAYS TO RESTORE CARDIAC FUNCTIONALITY AND TO REPLACE ABNORMAL OR NECROTIC CARDIOVASCULAR TISSUES. THERE IS CONSENSUS IN THE SCIENTIFIC AND MEDICAL COMMUNITIES ABOUT THE NEED FOR NEW BIOMATERIALS THAT HAVE THE PROPERTIES REQUIRED TO ENSURE CELL GRAFTING AND STIMULATE THE REGENERATION OF CARDIAC TISSUE. THE SEARCH FOR SUCH MATERIALS IS AN IMPORTANT CHALLENGE GIVEN THE INHERENT STRUCTURAL COMPLEXITY OF THE CARDIAC TISSUE: THE HEART IS A COMPLEX ORGAN WITH A VARIETY OF CELLS IN WHICH THE EXTRACELLULAR MATRIX, MAINLY BASED ON COLLAGEN FIBERS, NOT ONLY PROVIDES ADEQUATE BIOCHEMICAL SIGNALING BUT ALSO ACTS AS A SUPPORT THAT ALLOWS THE CORRECT CELLULAR CONNECTIONS AND AS A GUIDE FOR THE TRANSMISSION OF ELECTRICAL SIGNALS._x000D_ INDEED, IT IS KNOWN THAT CARDIOMYOCYTES OF NEWBORNS HAVE A PROLIFERATIVE BEHAVIOR THAT THOSE OF ADULTS LACK. ONE OF THE DIFFERENCES BETWEEN ADULT AND FETAL/NEWBORN¿S CARDIOMYOCYTES IS THE ABILITY OF THE LATTER TO TAKE LACTATE AS AN ENERGY SOURCE, WHICH CORRELATES WITH THE LACTATE-RICH ENVIRONMENT FOUND IN THE PLACENTA. PREVIOUS IN VITRO TESTS SUGGEST THAT IN THE PRESENCE OF LACTATE THE CARDIOMYOCYTES SHOW HIGHER RATES OF PROLIFERATION AND ABILITY TO FORM A FUNCTIONAL HEART MUSCLE._x000D_ THE PRESENT PROJECT PROPOSES THE DEVELOPMENT OF A NEW FAMILY OF ADVANCED BIOMATERIALS BASED ON ELASTIN-LIKE RECOMBINAMERS (ELRS), CAPABLE OF RELEASING LACTATE, FOR THE BIOFABRICATION OF CARDIAC PATCHES THROUGH ADVANCED PROCESSING TECHNOLOGIES SUCH AS 3D BIOPRINTING AND ELECTROSPINNING._x000D_ THE ELRS ENVISAGED IN THIS PROJECT ARE FORMED BY THE REPETITION OF SOME PEPTIDES THAT ARE FOUND IN NATURAL ELASTIN AND THAT HAVE PROPERTIES THAT ARE DIFFICULT TO FIND IN OTHER BIOMATERIALS, SUCH AS EXCELLENT BIOCOMPATIBILITY, ABILITY TO RESPOND TO EXTERNAL STIMULI, SELF-ASSEMBLY, OPTIMAL MECHANICAL AND CUSTOMIZABLE PROPERTIES OF THEIR HYDROGELS AND POSSIBILITY TO INCLUDE SPECIFIC BIOACTIVITIES, SUCH AS CELL ADHESION SEQUENCES AND PROTEASE SENSITIVE DOMAINS THAT GUARANTEE THAT THE SCAFFOLD IS DEGRADED IN A CONTROLLED MANNER OVER TIME SIMULTANEOUSLY WITH CELL PROLIFERATION AND EXTRACELLULAR MATRIX FORMATION. IN ADDITION, ELRS HAVE THE ABILITY TO BE CHEMICALLY MODIFIED TO CARRY REACTIVE GROUPS THAT ALLOW THEM TO RETAIN LACTATE THAT WILL SUBSEQUENTLY BE RELEASED IN A SUSTAINED MANNER AS A SOURCE OF ENERGY FOR CARDIOMYOCYTES._x000D_ THREE STRATEGIES FOR THE FORMATION OF LACTATE-BEARING CARDIAC SCAFFOLDS ARE PROPOSED AROUND THE ELRS: OBTAINING AN INJECTABLE HYDROGEL BY CHEMICAL CROSS-LINKING, OBTAINING A PATCH BASED ON ALIGNED NANOFIBERS USING ELECTROSPINNING TECHNOLOGY AND FABRICATION OF A CARDIAC SCAFFOLD WITH ADEQUATE STRUCTURE BY 3D PRINTING TECHNOLOGY. (English)
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Valladolid
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Identifiers
RTI2018-096320-B-C22
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