The Campus and buildings of the Universidad Central de Venezuela are considered to be Villanueva's masterwork. Built on the site of the old Hacienda Ibarra - which originally belonged to Simon Bolívar's family - and connected to the new city center around Plaza Venezuela, the project meant a massive undertaking of both urban planning and architectural design. The administration of Isaías Medina Angarita bought the Hacienda Ibarra in 1942 in order to give the University a larger location than the San Francisco Covent, giving Villanueva a unique opportunity to applied his conscious integration of art and architecture on a grand scale. This vast urban complex of about 2 square kilometres and included a total of 40 buildings and it remains one of the most successful applications of Modern Architecture in Latin America. Villanueva worked closely with all the artists who contributed with their oeuvres and personally supervised the project for over 25 years until the late 60's when his deteriorating health forced him to leave some buildings in the design stage.

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