title: Osteopromoting Reservoir of Stem Cells: Bioactive Mesoporous Nanocarrier/Collagen Gel through Slow-Releasing FGF18 and the Activated BMP Signaling.
abstract: Providing an osteogenic stimulatory environment is a key strategy to construct stem cell-based bone-equivalent tissues. Here we design a stem cell delivering gel matrix made of collagen (Col) with bioactive glass nanocarriers (BGn) that incorporate osteogenic signaling molecule, fibroblast growth factor 18 (FGF18), a reservoir considered to cultivate and promote osteogenesis of mesenchymal stem cells (MSCs). The presence of BGn in the gel was shown to enhance the osteogenic differentiation of MSCs, possibly due to the therapeutic role of ions released. The mesoporous nature of BGn was effective in loading FGF18 at large quantity, and the FGF18 release from the BGn-Col gel matrix was highly sustainable with almost a zero-order kinetics, over 4 weeks as confirmed by the green fluorescence protein signal change. The released FGF18 was effective in accelerating osteogenesis (alkaline phosphatase activity and bone related gene expressions) and bone matrix formation (osteopontin, bone sialoprotein, and osteocalcin production) of MSCs. This was attributed to the bone morphogenetic protein (BMP) signaling pathway, where the FGF18 release stimulated the endogenous secretion of BMP2 and the downstream signal Smad1/5/8. Taken together, the FGF18-BGn/Col gel is considered an excellent osteopromoting depot to support and signal MSCs for bone tissue engineering.
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University , Cheonan 330-714, South Korea.|Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University , Cheonan 330-714, South Korea.
authors.forename: Chinmaya
authors.initials: C
authors.lastname: Mahapatra
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University , Cheonan 330-714, South Korea.|Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University , Cheonan 330-714, South Korea.
authors.forename: Rajendra K
authors.initials: RK
authors.lastname: Singh
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University , Cheonan 330-714, South Korea.|Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University , Cheonan 330-714, South Korea.
authors.forename: Jung-Ju
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University , Cheonan 330-714, South Korea.|Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University , Cheonan 330-714, South Korea.
authors.forename: Kapil D
authors.initials: KD
authors.lastname: Patel
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University , Cheonan 330-714, South Korea.|Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University , Cheonan 330-714, South Korea.
authors.forename: Roman A
authors.initials: RA
authors.lastname: Perez
authors.affiliation: Department of Biochemistry, Inha University School of Medicine , Incheon 22212, Republic of Korea.
authors.forename: Jun-Hyeog
authors.initials: JH
authors.lastname: Jang
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University , Cheonan 330-714, South Korea.|Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University , Cheonan 330-714, South Korea.|Department of Biomaterials Science, School of Dentistry, Dankook University , Cheonan 330-714, South Korea.
authors.forename: Hae-Won
authors.initials: HW
authors.lastname: Kim
keywords: BMP signaling; bioactive glass nanocarrier; bone tissue engineering; growth factor delivery; mesenchymal stem cells; nanocomposite gel