title: Bio-inspired in situ crosslinking and mineralization of electrospun collagen scaffolds for bone tissue engineering.
abstract: Bone disorders are the most common cause of severe long term pain and physical disability, and affect millions of people around the world. In the present study, we report bio-inspired preparation of bone-like composite structures by electrospinning of collagen containing catecholamines and Ca(2+). The presence of divalent cation induces simultaneous partial oxidative polymerization of catecholamines and crosslinking of collagen nanofibers, thus producing mats that are mechanically robust and confer photoluminescence properties. Subsequent mineralization of the mats by ammonium carbonate leads to complete oxidative polymerization of catecholamines and precipitation of amorphous CaCO3. The collagen composite scaffolds display outstanding mechanical properties with Young's modulus approaching the limits of cancellous bone. Biological studies demonstrate that human fetal osteoblasts seeded on to the composite scaffolds display enhanced cell adhesion, penetration, proliferation, differentiation and osteogenic expression of osteocalcin, osteopontin and bone matrix protein when compared to pristine collagen or tissue culture plates. Among the two catecholamines, mats containing norepinephrine displayed superior mechanical, photoluminescence and biological properties than mats loaded with dopamine. These smart multifunctional scaffolds could potentially be utilized to repair and regenerate bone defects and injuries.
authors.affiliation: Anti-Infectives Research Group, Singapore Eye Research Institute, The Academia, 20 College Road, Discovery Tower, 169856, Singapore.
authors.forename: Chetna
authors.initials: C
authors.lastname: Dhand
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, Experimental Medicine Building, 636921, Singapore.
authors.forename: Seow Theng
authors.initials: ST
authors.lastname: Ong
authors.affiliation: Department of Electrical and Computer Engineering, National University of Singapore, 3 Engineering Drive 3, 117583, Singapore.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Dwivedi
authors.affiliation: Center for Nanofibers and Nanotechnology, Department of Mechanical Engineering, National University of Singapore, 119260, Singapore; Institute of Medical and Polymer Engineering, Technische Universität München, Boltzmannstrasse 15, 85748, Garching, Germany.
authors.forename: Silvia Marrero
authors.initials: SM
authors.lastname: Diaz
authors.affiliation: Center for Nanofibers and Nanotechnology, Department of Mechanical Engineering, National University of Singapore, 119260, Singapore.
authors.forename: Jayarama Reddy
authors.initials: JR
authors.lastname: Venugopal
authors.affiliation: Center for Nanofibers and Nanotechnology, Department of Mechanical Engineering, National University of Singapore, 119260, Singapore.
authors.forename: Balchandar
authors.initials: B
authors.lastname: Navaneethan
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, Experimental Medicine Building, 636921, Singapore.
authors.forename: Mobashar H U T
authors.initials: MH
authors.lastname: Fazil
authors.affiliation: Anti-Infectives Research Group, Singapore Eye Research Institute, The Academia, 20 College Road, Discovery Tower, 169856, Singapore; Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, 169857, Singapore.
authors.forename: Shouping
authors.initials: S
authors.lastname: Liu
authors.affiliation: Institute of Medical and Polymer Engineering, Technische Universität München, Boltzmannstrasse 15, 85748, Garching, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Seitz
authors.affiliation: Institute of Medical and Polymer Engineering, Technische Universität München, Boltzmannstrasse 15, 85748, Garching, Germany.
authors.forename: Erich
authors.initials: E
authors.lastname: Wintermantel
authors.affiliation: Anti-Infectives Research Group, Singapore Eye Research Institute, The Academia, 20 College Road, Discovery Tower, 169856, Singapore; Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, 169857, Singapore.
authors.forename: Roger W
authors.initials: RW
authors.lastname: Beuerman
authors.affiliation: Center for Nanofibers and Nanotechnology, Department of Mechanical Engineering, National University of Singapore, 119260, Singapore; Guangdong-Hongkong-Macau Institute of CNS Regeneration (GHMICR), Jinan University, Guangzhou, 510632, China. Electronic address: seeram@nus.edu.sg.
authors.forename: Seeram
authors.initials: S
authors.lastname: Ramakrishna
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, Experimental Medicine Building, 636921, Singapore. Electronic address: nkverma@ntu.edu.sg.
authors.forename: Navin K
authors.initials: NK
authors.lastname: Verma
authors.affiliation: Anti-Infectives Research Group, Singapore Eye Research Institute, The Academia, 20 College Road, Discovery Tower, 169856, Singapore; Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, 169857, Singapore. Electronic address: lakshminarayanan.rajamani@seri.com.sg.
authors.forename: Rajamani
authors.initials: R
authors.lastname: Lakshminarayanan
mesh_terms: D032701:Biomimetics / Q000295:instrumentation; D001846:Bone Development / Q000502:physiology*; D002113:Calcification, Physiologic / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry; D055119:Elastic Modulus / Q000502:physiology; D004595:Electroplating / Q000379:methods; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*; D023822:Tissue Engineering / Q000295:instrumentation* / Q000379:methods; D054457:Tissue Scaffolds
chemical_list: D003432:Cross-Linking Reagents; D003094:Collagen
keywords: Bone; Catecholamine; Collagen; Crosslinking; Electrospinning; Mineralization