Multiscale manufacturing of Janus membranes for oral tissue regeneration

Native tissue interfaces exhibit spatially heterogeneous structures and functions, with adjacent tissues imposing distinct and sometimes competing requirements on regenerative materials. Reproducing such organization within a thin membrane remains a manufacturing challenge, requiring the coordinated control of microstructures across multiple length scales, local composition, and biological function. Here, we developed a multiscale manufacturing strategy for biodegradable polyhydroxyalkanoate (PHA)-based membranes by integrating electrospinning with electrohydrodynamic direct writing. The complementary deposition modes enabled the construction of a dense fibrous layer and an ordered porous framework within a single membrane, while spatially localized functional components further introduced compositional differentiation. Together, these features generated a Janus architecture with distinct structural and functional characteristics on its two sides. Scanning electron microscopy and cross-sectional characterization confirmed the well-defined dense and porous architectures, while elemental mapping demonstrated the spatial differentiation of functional components. Functional evaluation showed that the barrier-oriented side markedly inhibited bacterial adhesion and survival. Transcriptomic analysis further revealed distinct cellular transcriptional responses to different structural and compositional configurations, suggesting that manufacturing-defined local microenvironments can influence cell behavior beyond providing passive physical organization. These findings demonstrate that multiscale manufacturing can do more than integrate structures of different dimensions: it enables the spatial coordination of structural architecture, local composition, and biological function within a unified membrane system. By translating the heterogeneous requirements of adjacent tissues into spatially differentiated material interfaces, this strategy provides a bioinspired manufacturing route for regenerative membranes and offers a potentially extensible framework for the reconstruction of complex tissue interfaces.

Dr. Xu Zhang is an Associate Professor at Peking University School and Hospital of Stomatology. He is a committee member of the Biomanufacturing Engineering Branch of the Chinese Mechanical Engineering Society. His research focuses on the biofabrication and functional restoration of tissue interfaces, particularly the controlled fabrication of complex tissue architectures using 3D printing and the regulation of interfacial microenvironments. He has led projects supported by the General Program of NSFC and a subproject under the National Key R&D Program of China. He has published more than 30 papers as a (co-)first or (co-)corresponding author, in journals such as Science Advances and Trends in Biotechnology, and has filed more than 10 invention patent applications. He was selected for the Beijing Nova Program and the Young Elite Scientists Sponsorship Program by the Beijing Association for Science and Technology. His honors include the Second Prize of the Chinese Medical Science and Technology Award and a Gold Medal at the 49th International Exhibition of Inventions Geneva. His current research focuses on 3D printing-enabled organoid engineering and strategies to direct tissue regeneration, with particular interest in applying multimaterial printing to reconstruct soft–hard tissue interfaces.