title: Accelerated Bone Regeneration by Two-Photon Photoactivated Carbon Nitride Nanosheets.
abstract: Human bone marrow-derived mesenchymal stem cells (hBMSCs) present promising opportunities for therapeutic medicine. Carbon derivatives showed only marginal enhancement in stem cell differentiation toward bone formation. Here we report that red-light absorbing carbon nitride (C3N4) sheets lead to remarkable proliferation and osteogenic differentiation by runt-related transcription factor 2 (Runx2) activation, a key transcription factor associated with osteoblast differentiation. Accordingly, highly effective hBMSCs-driven mice bone regeneration under red light is achieved (91% recovery after 4 weeks compared to 36% recovery in the standard control group in phosphate-buffered saline without red light). This fast bone regeneration is attributed to the deep penetration strength of red light into cellular membranes via tissue and the resulting efficient cell stimulation by enhanced photocurrent upon two-photon excitation of C3N4sheets near cells. Given that the photoinduced charge transfer can increase cytosolic Ca2+accumulation, this increase would promote nucleotide synthesis and cellular proliferation/differentiation. The cell stimulation enhances hBMSC differentiation toward bone formation, demonstrating the therapeutic potential of near-infrared two-photon absorption of C3N4sheets in bone regeneration and fracture healing.
authors.affiliation: Department of Chemistry and §School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , 50 UNIST-gil, Ulsan 44919, Korea.
authors.forename: Jitendra N
authors.initials: JN
authors.lastname: Tiwari
authors.affiliation: Department of Chemistry and §School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , 50 UNIST-gil, Ulsan 44919, Korea.
authors.forename: Young-Kyo
authors.initials: YK
authors.lastname: Seo
authors.affiliation: Department of Chemistry and §School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , 50 UNIST-gil, Ulsan 44919, Korea.
authors.forename: Taeseung
authors.initials: T
authors.lastname: Yoon
authors.affiliation: Department of Chemistry and §School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , 50 UNIST-gil, Ulsan 44919, Korea.
authors.forename: Wang Geun
authors.initials: WG
authors.lastname: Lee
authors.affiliation: Department of Chemistry and §School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , 50 UNIST-gil, Ulsan 44919, Korea.
authors.forename: Woo Jong
authors.initials: WJ
authors.lastname: Cho
authors.affiliation: Department of Chemistry and §School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , 50 UNIST-gil, Ulsan 44919, Korea.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Yousuf
authors.affiliation: Department of Chemistry and §School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , 50 UNIST-gil, Ulsan 44919, Korea.
authors.forename: Ahmad M
authors.initials: AM
authors.lastname: Harzandi
authors.affiliation: Department of Chemistry and §School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , 50 UNIST-gil, Ulsan 44919, Korea.
authors.forename: Du-Seok
authors.initials: DS
authors.lastname: Kang
authors.affiliation: Department of Chemistry and §School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , 50 UNIST-gil, Ulsan 44919, Korea.
authors.forename: Kwang-Youn
authors.initials: KY
authors.lastname: Kim
authors.affiliation: Department of Chemistry and §School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , 50 UNIST-gil, Ulsan 44919, Korea.
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
authors.affiliation: Department of Chemistry and §School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , 50 UNIST-gil, Ulsan 44919, Korea.
authors.forename: Kwang S
authors.identifier: 0000-0002-6929-5359
authors.initials: KS
authors.lastname: Kim
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D003393:Cranial Sutures / Q000187:drug effects; D004195:Disease Models, Animal; D006367:HeLa Cells; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D049329:Nanostructures / Q000737:chemistry*; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010012:Osteogenesis / Q000187:drug effects; D017785:Photons; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D009570:Nitriles; D017319:Photosensitizing Agents; C011206:cyanogen
keywords: bone regeneration; carbon nitride nanosheets; mesenchymal stem cells; osteogenic differentiation; proliferation; two-photon materials