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Fatemeh Ejeian,1,2 Amir Razmjou,1,3 Mohammad Hossein Nasr-Esfahani,2 Munirah Mohammad,3 Fereshteh Karamali,2 Majid Ebrahimi Warkiani,4 Mohsen Asadnia,5 Vicki Chen6 1Department of Biotechnology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan 73441-81746, Iran; 2Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran; 3UNESCO Center for Membrane Technology, School of Chemical Engineering, University of New South Wales, Sydney, NSW, 2052, Australia; 4School of Biomedical Engineering, University of Technology Sydney, Sydney, NSW, 2007, Australia; 5School of Engineering, Macquarie University, Sydney, NSW, 2109, Australia; 6School of Chemical Engineering, University of Queensland, Brisbane, QLD, 4072, AustraliaCorrespondence: Amir RazmjouUNESCO Center for Membrane Technology, School of Chemical Engineering, University of New South Wales, Sydney, NSW 2052, AustraliaTel +61 (2) 9385 4341Fax +61 (2) 9385 5966Email amirr@unsw.edu.auMohammad Hossein Nasr-Esfahani Department of Animal Biotechnology, Cell Science Research CenterRoyan Institute for Biotechnology, ACECR, Isfahan, IranTel +98 31 95015680Fax +98 31 95015687Email mh.nasr-esfahani@royaninstitute.orgPurpose: Despite the significant advances in modeling of biomechanical aspects of cell microenvironment, it remains a major challenge to precisely mimic the physiological condition of the particular cell niche. Here, the metal–organic frameworks (MOFs) have been introduced as a feasible platform for multifactorial control of cell-substrate interaction, given the wide range of physical and mechanical properties of MOF materials and their structural flexibility.Results: In situ crystallization of zeolitic imidazolate framework-8 (ZIF-8) on the polydopamine (PDA)-modified membrane significantly raised surface energy, wettability, roughness, and stiffness of the substrate. This modulation led to an almost twofold increment in the primary attachment of dental pulp stem cells (DPSCs) compare to conventional plastic culture dishes. The findings indicate that polypropylene (PP) membrane modified by PDA/ZIF-8 coating effectively supports the growth and proliferation of DPSCs at a substantial rate. Further analysis also displayed the exaggerated multilineage differentiation of DPSCs with amplified level of autocrine cell fate determination signals, like BSP1, BMP2, PPARG, FABP4, ACAN, and COL2A. Notably, osteogenic markers were dramatically overexpressed (more than 100-folds rather than tissue culture plate) in response to biomechanical characteristics of the ZIF-8 layer.Conclusion: Hence, surface modification of cell culture platforms with MOF nanostructures proposed as a powerful nanomedical approach for selectively guiding stem cells for tissue regeneration. In particular, PP/PDA/ZIF-8 membrane presented ideal characteristics for using as a barrier membrane for guided bone regeneration (GBR) in periodontal tissue engineering.Keywords: metal–organic framework, mesenchymal stem cell, ZIF-8, cell culture platform, barrier membrane