title: Feasibility of silica-hybridized collagen hydrogels as three-dimensional cell matrices for hard tissue engineering.
abstract: Exploiting hydrogels for the cultivation of stem cells, aiming to provide them with physico-chemical cues suitable for osteogenesis, is a critical demand for bone engineering. Here, we developed hybrid compositions of collagen and silica into hydrogels via a simple sol-gel process. The physico-chemical and mechanical properties, degradation behavior, and bone-bioactivity were characterized in-depth; furthermore, the in vitro mesenchymal stem cell growth and osteogenic differentiation behaviors within the 3D hybrid gel matrices were communicated for the first time. The hydrolyzed and condensed silica phase enabled chemical links with the collagen fibrils to form networked hybrid gels. The hybrid gels showed improved chemical stability and greater resistance to enzymatic degradation. The in vitro apatite-forming ability was enhanced by the hybrid composition. The viscoelastic mechanical properties of the hybrid gels were significantly improved in terms of the deformation resistance to an applied load and the modulus values under a dynamic oscillation. Mesenchymal stem cells adhered well to the hybrid networks and proliferated actively with substantial cytoskeletal extensions within the gel matrices. Of note, the hybrid gels substantially reduced the cell-mediated gel contraction behaviors, possibly due to the stiffer networks and higher resistance to cell-mediated degradation. Furthermore, the osteogenic differentiation of cells, including the expression of bone-associated genes and protein, was significantly upregulated within the hybrid gel matrices. Together with the physico-chemical and mechanical properties, the cellular behaviors observed within 3D gel matrices, being different from the previous approaches reported on 2D substrates, provide new information on the feasibility and usefulness of the silica-collagen system for stem cell culture and tissue engineering of hard tissues.
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University Graduate School, Cheonan, Republic of Korea.
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Yu
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University Graduate School, Cheonan, Republic of Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University Graduate School, Cheonan, Republic of Korea.
authors.forename: Seog-Jin
authors.initials: SJ
authors.lastname: Seo
authors.affiliation: Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University Graduate School, Cheonan, Republic of Korea Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, University College London, London, UK.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Knowles
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University Graduate School, Cheonan, Republic of Korea Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, Republic of Korea kimhw@dku.edu.
authors.forename: Hae-Won
authors.initials: HW
authors.lastname: Kim
mesh_terms: D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry*; D005240:Feasibility Studies; D020100:Hydrogels; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D051381:Rats; D012822:Silicon Dioxide / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D023822:Tissue Engineering
chemical_list: D020100:Hydrogels; D012822:Silicon Dioxide; D003094:Collagen
keywords: Bone tissue engineering; collagen gel; hybrids; osteogenesis; silica; stability