title: A moldable putty containing silk fibroin yolk shell particles for improved hemostasis and bone repair.
abstract: During minimally invasive orthopedic surgeries, surgical intervention is required at two stages; to attain hemostasis and subsequently to implant the bone graft or its substitute. There is an apparent need for a material which can simultaneously control bone bleeding and provide support for bone repair. In this work, a moldable putty, which can be applied to bone defects (usually irregular in shape), was developed to address this need. It comprises of a hemostatic factor thrombin, osteoinductive "yolk-shell" particles containing bone growth factor (BMP-2), and an osteoconductive component hydroxyapatite. The yolk shell particles allowed controlled release of BMP-2 and showed significantly enhanced osteogenic differentiation of C2C12 (mouse myoblast) cells as demonstrated by increased alkaline phosphatase (ALP) activity and relative gene expressions of osteogenic differentiation markers. These particles were assembled into a moldable putty by mixing them with hydroxyapatite and silk fibroin solution (binding agent) supplemented with thrombin. The putty showed non-cytotoxicity, hemostatic ability, sustained release of BMP-2 and induced increased mineralization in C2C12 cells. This putty, if applied to bone defects during surgeries, may help attain hemostasis and may enhance bone repair by providing sustained release of bone growth factors.
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore, -117576, Singapore.
authors.forename: Kushagra
authors.initials: K
authors.lastname: Saran
authors.forename: Pujiang
authors.initials: P
authors.lastname: Shi
authors.forename: Shashi
authors.initials: S
authors.lastname: Ranjan
authors.forename: James C H
authors.initials: JC
authors.lastname: Goh
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001671:Biochemistry / Q000379:methods; D012831:Bombyx / Q000737:chemistry; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000235:genetics / Q000493:pharmacokinetics*; D001861:Bone Regeneration / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D017886:Durapatite / Q000737:chemistry; D005349:Fibroins / Q000737:chemistry* / Q000494:pharmacology*; D006490:Hemostatics / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D032448:Myoblasts, Skeletal / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry*; D013917:Thrombin / Q000737:chemistry
chemical_list: D055396:Bone Morphogenetic Protein 2; D006490:Hemostatics; D005349:Fibroins; D017886:Durapatite; D000469:Alkaline Phosphatase; D013917:Thrombin
keywords: BMP-2 delivery; hydroxyapatite; moldable putty; silk fibroin; yolk-shell particle