University-industry collaborations need a paradigm shift from the traditional one-way knowledge transfer model to a two-way knowledge co-creation model, according to a new report from the Big Innovation Centre (BIC) — Collaborate to Innovate. The authors propose that a shift toward a knowledge co-creation paradigm focused on holistic relationships between university and industry, specifically small- and medium-sized businesses (SMEs), will have more significant economic and societal impacts than the traditional one-way knowledge transfer that relies primarily on patents, licensing and startup formation. Although focused on the innovation ecosystem in the UK, the paper addresses four universally important questions on how to achieve successful university-business collaborations via a co-creation model: