Enzymes are essential catalysts in numerous biological processes due to their efficiency, specificity, and selectivity. To enhance their stability and reusability, enzyme immobilization onto solid supports is crucial. Hierarchically porous metal-organic frameworks (HP-MOFs), with tunable meso- and macropores, have emerged as a promising solution for enzyme encapsulation, significantly improving catalytic performance. This review examines the development of various metal-based HP-MOFs, such as: iron, copper, zirconium, zinc, aluminum, and chromium, specifically designed for enzyme immobilization. The focus is on novel synthesis strategies, including functional group incorporation and hierarchical pore design, which optimize enzyme performance. Key advancements in immobilization techniques, such as: adsorption, covalent binding, in situ encapsulation, and post-synthetic infiltration, are also discussed. The review addresses the often-overlooked issue of HP-MOF toxicity, presenting both challenges and benefits. It also emphasizes the regulatory implications of HP-MOF applications, particularly in the food, pharmaceutical, and biomedical sectors, offering insights into how these materials can be safely integrated into these industries. Data from various studies demonstrate significant improvements in enzyme activity retention, stability, and efficiency in biocatalytic applications. Additionally, diverse applications in biocatalysis, biodiesel production, biosensing, and disease diagnosis are explored. A key feature of this review is the focus on advancing HP-MOF-enzyme composites toward higher technology readiness levels (TRLs), a topic not comprehensively covered in the literature. This review provides valuable insights for researchers aiming to optimize HP-MOFs for enzyme encapsulation and industrial biotechnological applications.
Patil et al. (2026) studied this question.