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Cities increasingly have to find innovative ways to address challenges arising from climate change and urbanization. Nature-based solutions (NBS) have been gaining attention as multifunctional solutions that may help cities to address these challenges. However, the adoption and implementation of these solutions have been limited due to various barriers. This study aims to identify a taxonomy of dominant barriers to the uptake and implementation of NBS and their relationships. Fifteen barriers are identified from the literature and expert interviews and then ranked through a questionnaire. Interpretive Structural Modeling (ISM) serves to identify the mutual interdependencies among these barriers, which results in a structural model of six levels. Subsequently, Cross-impact matrix multiplication applied to classification (MICMAC analysis) is used to classify the barriers into four categories. The results suggest that political, institutional and knowledge-related barriers are the most dominant barriers to NBS. Cities that intend to apply NBS can draw on these findings, especially by more effectively prioritizing and managing their actions.