Biocatalytic hydrogen-bonded organic frameworks: Design and biomedical applications

Hydrogen-bonded organic frameworks (HOFs), characterized by precisely engineered long-range ordered structures and tunable hydrogen-bonding networks, have emerged as a promising novel class of porous crystalline materials, particularly for catalytic applications. The integration of HOFs with bioactive components enables the rational construction of HOFs-based biocatalytic composites, yielding hybrid systems with exceptional structural stability, enhanced catalytic efficiency, and synergistic functionalities, positioning them as promising next-generation materials for diverse biomedical applications. Nevertheless, research on HOFs-based biocatalytic systems remains nascent, lacking comprehensive systematic analysis. To address this gap, this review systematically summarizes recent advances in HOFs-based biocatalysts. It details modular assembly strategies, discusses catalytic mechanisms and catalytic enhancement strategy, and highlights their emerging applications in biologically relevant domains, including biomedical engineering, enzymatic catalysis, and environmental science. Furthermore, the review analyzes the dilemmas and challenges facing the future development of HOFs-based biocatalysts, and proposes potential solution strategies, such as the trade-off between stability and activity, multifunctional integration, and addressing long-term biosafety concerns. Finally, it outlines strategic research directions to advance this rapidly evolving field and envisions future prospects for these emerging materials, providing a roadmap for their translational development.