This research aims to understand how certain mechanisms promote cross-border collaboration strategies (CBCS) in new research and development institutions (NRDIs) and improve their academic entrepreneurship within the Triple Helix. Multiple case studies of NRDIs were conducted by proposing a ‘mission-structure-mechanisms-outcomes’ model with the open innovation concept. The findings pinpoint the important role played by CBCS in helping NRDI construct, a micro-collaborative and academic entrepreneurial ecosystem, and improving academic entrepreneurial performance. The following are the key to form CBCS and improve its entrepreneurial performance: to focus the core mission of NRDI on the research results commercialization, to establish cross-border integration, business incubation system and diversified incentives. Results from these case studies provide new insights into the role played by CBCS of NRDIs for practitioners and policymakers in this field.
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