title: Cell-free 3D scaffold with two-stage delivery of miRNA-26a to regenerate critical-sized bone defects.
abstract: MicroRNAs (miRNAs) are being developed to enhance tissue regeneration. Here we show that a hyperbranched polymer with high miRNA-binding affinity and negligible cytotoxicity can self-assemble into nano-sized polyplexes with a 'double-shell' miRNA distribution and high transfection efficiency. These polyplexes are encapsulated in biodegradable microspheres to enable controllable two-stage (polyplexes and miRNA) delivery. The microspheres are attached to cell-free nanofibrous polymer scaffolds that spatially control the release of miR-26a. This technology is used to regenerate critical-sized bone defects in osteoporotic mice by targeting Gsk-3β to activate the osteoblastic activity of endogenous stem cells, thus addressing a critical challenge in regenerative medicine of achieving cell-free scaffold-based miRNA therapy for tissue engineering.
authors.affiliation: Department of Biologic and Materials Science, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Biologic and Materials Science, University of Michigan, Ann Arbor, Michigan 48109, USA.|State Key Laboratory of Military Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cardiac Surgery, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jihua
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Biologic and Materials Science, University of Michigan, Ann Arbor, Michigan 48109, USA.|Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA.|Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, Michigan 48109, USA.|Department of Materials Science and Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Peter X
authors.initials: PX
authors.lastname: Ma
mesh_terms: D000818:Animals; D001861:Bone Regeneration; D002478:Cells, Cultured; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D048091:Guided Tissue Regeneration; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000008:administration & dosage*; D010024:Osteoporosis / Q000628:therapy*; D011108:Polymers / Q000138:chemical synthesis*; D054457:Tissue Scaffolds
chemical_list: D035683:MicroRNAs; C543693:Mirn26 microRNA, mouse; D011108:Polymers; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3