FULL PAPER m-journal.d updates Remote Tuning of Built-In Magnetoelectric Microenvironment to Promote Bone Regeneration by Modulating Cellular Exposure to Arginylglycylaspartic Acid Peptide Wenwen Liu, Fengyi Zhang, Yuanyang Yan, Chenguang Zhang, Han Zhao, Boon Chin Heng, Ying Huang, Yang Shen, Jinxing Zhang, Lili Chen, Xiufang Wen, and Xuliang Deng 1. Introduction Mimicking the endogenous physical microenvironment is a promising strategy for biomaterial-mediated tissue regeneration. However, precise A major strategy in tissue engineerin control of physical cues such as electric/magnetic fields within extracellular is to mimic the biophysical properties of environments to facilitate tissue regeneration remains a formidable challenge target tissues and various critical aspects of the extracellular environment to Here, remote tuning of the magnetoelectric microenvironment is achieved modulate cell function via celk-material by a built-in CoFe, O4/poly(vinylidene fluoridetrifluoroethylene)[P(VDF-TrFE) nteractions H Recently, mimicking the magnetoelectric membrane for effective bone regeneration. The magneto. endogenous physical microenvironment electric microenvironment from the nanocomposite membranes promotes via implanted biomaterials has emerged as osteogenic differentiation of bone marrow mesenchymal stem cells(BI a new strategy for recapitulating the extr cellular microenvironment at the wound/ MSCs) and enhances bone defect regeneration by increasing cellular expo injury site to facilitate tissue regenera- sure and integrin binding to arginylglycylaspartic acid peptide, as predicte tion 2 Endogenous magnetoelectric prop- by molecular dynamics simulations. Moreover, BM-MSCs are directed to the erty is an integral aspect of the natural osteogenic lineage by osteoimmuomodulation which involves accelerating microenvironment of native transition from an initial inflammatory immune response to a pro- healing tissues l and extensive research has dem regenerative immune response. This work offers a strategy to mimic the onstrated that the osteogenic differentia ion, chondrogenic differentiation, PI and magnetoelectric microenvironment for achieving precise and effective tissue erogenic differentiation 6 of mesen- regenerative therapies, as well as provides fundamental insights into the chymal stem cell (MSC)can be modulated biological effects driven by the built-in magnetoelectric membrane, which can by the application of an external electro- be remotely tuned to precisely modulate osteogenesis in situ magnetic field. The magnetoelectric field provided by extracorporeal devices often Dr. W. Liu, Dr. F. Zhang, D Dr. Y. Huang, Prof Prof B. C. he NMPA Key Laboratory for l ials National E Central Laboratory Laboratory for Digital and Peking University School and Hospital of Stomatology Beijing 100081, P R China eking University School an f Stomatal Beijing 100081, P.R. China E- mail: kad Department of Materials Science and Engineering Dr Y Yan. Prof. X Wen The School of Chemistry and Chemical Engineering Beijing 100084, China South China University of Technology Guangzhou Prof. .Zhal Guangzhou 510640, P.R. China E-mail:xiwen@scut.edu.cn Dr. C. Zhang China cal Hospital Prof. L Chen Department of Stomatology Union Hospital Tongji Medical College Guangzhou 510280, China Huazhong University of Science and Technology he ORCID identification number(s)for the author(s)of this article Wuhan 430022, P. R. China canbefoundunderhttps://doi.org/0.1002/adfm.202006226 Do:10.002/adfm202006226 Adv Funct. Mater. 2020. 2006226 2006226of o 2020 Wiley-VCH GmbHwww.afm-journal.de 2006226 (1 of 11) © 2020 Wiley-VCH GmbH Full Paper Remote Tuning of Built-In Magnetoelectric Microenvironment to Promote Bone Regeneration by Modulating Cellular Exposure to Arginylglycylaspartic Acid Peptide Wenwen Liu, Fengyi Zhang, Yuanyang Yan, Chenguang Zhang, Han Zhao, Boon Chin Heng, Ying Huang, Yang Shen, Jinxing Zhang, Lili Chen, Xiufang Wen,* and Xuliang Deng* Mimicking the endogenous physical microenvironment is a promising strategy for biomaterial-mediated tissue regeneration. However, precise control of physical cues such as electric/magnetic fields within extracellular environments to facilitate tissue regeneration remains a formidable challenge. Here, remote tuning of the magnetoelectric microenvironment is achieved by a built-in CoFe2O4/poly(vinylidene fluoridetrifluoroethylene) [P(VDF-TrFE)] magnetoelectric membrane for effective bone regeneration. The magneto￾electric microenvironment from the nanocomposite membranes promotes osteogenic differentiation of bone marrow mesenchymal stem cells (BM￾MSCs) and enhances bone defect regeneration by increasing cellular expo￾sure and integrin binding to arginylglycylaspartic acid peptide, as predicted by molecular dynamics simulations. Moreover, BM-MSCs are directed to the osteogenic lineage by osteoimmuomodulation which involves accelerating transition from an initial inflammatory immune response to a pro-healing regenerative immune response. This work offers a strategy to mimic the magnetoelectric microenvironment for achieving precise and effective tissue regenerative therapies, as well as provides fundamental insights into the biological effects driven by the built-in magnetoelectric membrane, which can be remotely tuned to precisely modulate osteogenesis in situ. DOI: 10.1002/adfm.202006226 Dr. W. Liu, Dr. F. Zhang, Dr. H. Zhao, Dr. Y. Huang, Prof. X. Deng NMPA Key Laboratory for Dental Materials National Engineering Laboratory for Digital and Material Technology of Stomatology Department of Geriatric Dentistry Peking University School and Hospital of Stomatology Beijing 100081, P. R. China E-mail: kqdengxuliang@bjmu.edu.cn Dr. Y. Yan, Prof. X. Wen The School of Chemistry and Chemical Engineering South China University of Technology Guangzhou Guangzhou 510640, P. R. China E-mail: xfwen@scut.edu.cn Dr. C. Zhang Stomatological Hospital Southern Medical University Guangzhou 510280, China Prof. B. C. Heng Central Laboratory Peking University School and Hospital of Stomatology Beijing 100081, P. R. China Prof. Y. Shen State Key Laboratory of New Ceramics and Fine Processing Department of Materials Science and Engineering Tsinghua University Beijing 100084, China Prof. J. Zhang Department of Physics Beijing Normal University Beijing 100875, China Prof. L. Chen Department of Stomatology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022, P. R. China 1. Introduction A major strategy in tissue engineering is to mimic the biophysical properties of target tissues and various critical aspects of the extracellular environment to modulate cell function via cell–material interactions.[1] Recently, mimicking the endogenous physical microenvironment via implanted biomaterials has emerged as a new strategy for recapitulating the extra￾cellular microenvironment at the wound/ injury site to facilitate tissue regenera￾tion.[2] Endogenous magnetoelectric prop￾erty is an integral aspect of the natural biophysical microenvironment of native tissues,[3] and extensive research has dem￾onstrated that the osteogenic differentia￾tion,[4] chondrogenic differentiation,[5] and neurogenic differentiation[6] of mesen￾chymal stem cell (MSC) can be modulated by the application of an external electro￾magnetic field. The magnetoelectric field provided by extracorporeal devices often The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adfm.202006226. Adv. Funct. Mater. 2020, 2006226