RGD mutation of the heparin binding II fragment of fibronectin for guiding mesenchymal stem cell behavior on titanium surfaces

Installing bioactivity on metallic biomaterials by mimicking the extracellular matrix (ECM) is crucial for stimulating specific cellular responses to ultimately promote tissue regeneration. Fibronectin is an ECM protein commonly used for biomaterial functionalization. The use of fibronectin recombin...

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Detalhes bibliográficos
Autores: Guillem Martí, Jordi|||0000-0003-0307-2221, Gelabert París, Maria, Heras Parets, Aina, Pegueroles Neyra, Marta|||0000-0002-7895-8337, Ginebra Molins, Maria Pau|||0000-0002-4700-5621, Manero Planella, José María|||0000-0002-1673-4389
Formato: artículo
Fecha de publicación:2019
País:España
Recursos:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/130220
Acesso em linha:https://hdl.handle.net/2117/130220
https://dx.doi.org/10.1021/acsami.8b17138
Access Level:acceso abierto
Palavra-chave:Fibronectins
Growth factors
Osseointegration
Recombinant proteins
Titanium
fibronectin
growth factor
mutation
osseointegration
recombinant protein
titanium
Factors de creixement
Osseointegració
Proteïnes recombinants
Titani
Àrees temàtiques de la UPC::Enginyeria dels materials
Descrição
Resumo:Installing bioactivity on metallic biomaterials by mimicking the extracellular matrix (ECM) is crucial for stimulating specific cellular responses to ultimately promote tissue regeneration. Fibronectin is an ECM protein commonly used for biomaterial functionalization. The use of fibronectin recombinant fragments is an attractive alternate to the use of full-length fibronectin because of the relatively low cost and facility of purification. However, it is necessary to combine more than one fragment, for example, the cell attachment site and the heparin binding II (HBII), either mixed or in one molecule, to obtain complete activity. In the present study, we proposed to install adhesion capacity to the HBII fragment by an RGD gain-of-function DNA mutation, retaining its cell differentiation capacity and thereby producing a small and very active protein fragment. The novel molecule, covalently immobilized onto titanium surfaces, maintained the growth factor-binding capacity and stimulated cell spreading, osteoblastic cell differentiation, and mineralization of human mesenchymal stem cells compared to the HBII native protein. These results highlight the potential capacity of gain-of-function DNA mutations in the design of novel molecules for the improvement of osseointegration properties of metallic implant surfaces.