[5] DeSimone previously held a joint appointment as the Chancellor's Eminent Professor of Chemistry at the University of North Carolina at Chapel Hill and William R. Kenan Jr.

[12] In the 1990s, at the University of North Carolina at Chapel Hill, he developed an environmentally friendly manufacturing process that relies on supercritical carbon dioxide instead of water and bio-persistent surfactants for the creation of fluoropolymers or high-performance plastics, such as Teflon.

[15] As a professor at the University of North Carolina at Chapel Hill and North Carolina State University, DeSimone and members of his academic laboratory also developed the nanoparticle fabrication technology, PRINT (Particle Replication in Non-Wetting Templates), leading DeSimone and students to co-found the company Liquidia Technologies in 2004.

[citation needed] In 2015, DeSimone and colleagues published a paper in Science Magazine on their invention of a rapid polymer 3D printing technology, Continuous Liquid Interface Production (CLIP).

[18][19] The printers are used to make end-use parts and products in several industries,[20] including by the companies Adidas,[21][22] Resolution Medical,[23][24] and Ford.