title: Therapeutic-designed electrospun bone scaffolds: mesoporous bioactive nanocarriers in hollow fiber composites to sequentially deliver dual growth factors.
abstract: A novel therapeutic design of nanofibrous scaffolds, holding a capacity to load and deliver dual growth factors, that targets bone regeneration is proposed. Mesoporous bioactive glass nanospheres (MBNs) were used as bioactive nanocarriers for long-term delivery of the osteogenic enhancer fibroblast growth factor 18 (FGF18). Furthermore, a core-shell structure of a biopolymer fiber made of polyethylene oxide/polycaprolactone was introduced to load FGF2, another type of cell proliferative and angiogenic growth factor, safely within the core while releasing it more rapidly than FGF18. The prepared MBNs showed enlarged mesopores of about 7 nm, with a large surface area and pore volume. The protein-loading capacity of MBNs was as high as 13% when tested using cytochrome C, a model protein. The protein-loaded MBNs were smoothly incorporated within the core of the fiber by electrospinning, while preserving a fibrous morphology. The incorporation of MBNs significantly increased the apatite-forming ability and mechanical properties of the core-shell fibers. The possibility of sequential delivery of two experimental growth factors, FGF2 and FGF18, incorporated either within the core-shell fiber (FGF2) or within MBNs (FGF18), was demonstrated by the use of cytochrome C. In vitro studies using rat mesenchymal stem cells demonstrated the effects of the FGF2-FGF18 loadings: significant stimulation of cell proliferation as well as the induction of alkaline phosphate activity and cellular mineralization. An in vivo study performed on rat calvarium defects for 6 weeks demonstrated that FGF2-FGF18-loaded fiber scaffolds had significantly higher bone-forming ability, in terms of bone volume and density. The current design utilizing novel MBN nanocarriers with a core-shell structure aims to release two types of growth factors, FGF2 and FGF18, in a sequential manner, and is considered to provide a promising therapeutic scaffold platform that is effective for bone regeneration.
authors.affiliation: Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Min Sil
authors.initials: MS
authors.lastname: Kang
authors.affiliation: Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Joong-Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Rajendra K
authors.initials: RK
authors.lastname: Singh
authors.affiliation: Department of Biochemistry, College of Medicine, Inha University, Incheon, Republic of Korea.
authors.forename: Jun-Hyeog
authors.initials: JH
authors.lastname: Jang
authors.affiliation: Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan 330-714, Republic of Korea. Electronic address: kimhw@dku.edu.
authors.forename: Hae-Won
authors.initials: HW
authors.lastname: Kim
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006868:Hydrolysis; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D054118:Nanospheres / Q000737:chemistry* / Q000648:ultrastructure; D010012:Osteogenesis / Q000187:drug effects; D016062:Porosity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013718:Tensile Strength / Q000187:drug effects; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C113569:fibroblast growth factor 18; D016222:Fibroblast Growth Factor 2; D005346:Fibroblast Growth Factors; D045304:Cytochromes c
keywords: Bioactive nanocarriers; Bone regeneration; Controlled release; Growth factor delivery; Nanofiber scaffolds