title: Covalent cross-links in polyampholytic chitosan fibers enhances bone regeneration in a rabbit model.
abstract: Chitosan fibers were prepared in citric acid bath, pH 7.4 and NaOH solution at pH 13, to form ionotropically cross-linked and uncross-linked fibers, respectively. The fibers formed in citric acid bath were further cross-linked via carbodiimide chemistry; wherein the pendant carboxyl moieties of citric acid were used for new amide bond formation. Moreover, upon covalent cross-linking in the ionically gelled citrate-chitosan fibers, incomplete conversion of the ion pairs to amide linkages took place resulting in the formation of a dual network structure. The dual cross-linked fibers displayed improved mechanical property, higher stability against enzymatic degradation, hydrophobicity and superior bio-mineralization compared to the uncross-linked and native citrate cross-linked fibers. Additionally, upon cyclic loading, the ion pairs in the dual cross-linked fibers dissociated by dissipating energy and reformed during the relaxation period. The twin property of elasticity and energy dissipation mechanism makes the dual cross-linked fiber unique under dynamic mechanical conditions. The differences in the physico-chemical characteristics were reflected in protein adsorption, which in turn influenced the cellular activities on the fibers. Compared to the uncross-linked and ionotropically cross-linked fibers, the dual cross-linked fibers demonstrated higher proliferation and osteogenic differentiation of the MSCs in vitro as well as better osseous tissue regeneration in a rabbit model.
authors.affiliation: Biomaterials and Tissue Engineering Laboratory, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.
authors.forename: Paulomi
authors.initials: P
authors.lastname: Ghosh
authors.affiliation: Biomaterials and Tissue Engineering Laboratory, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.
authors.forename: Arun Prabhu
authors.initials: AP
authors.lastname: Rameshbabu
authors.affiliation: Polymer Chemistry Laboratory, Department of Applied Chemistry, Indian School of Mines, Dhanbad 826004, India.
authors.forename: Dipankar
authors.initials: D
authors.lastname: Das
authors.affiliation: Biomaterials and Tissue Engineering Laboratory, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.
authors.forename: Nimmy K
authors.initials: NK
authors.lastname: Francis
authors.affiliation: Biomaterials and Tissue Engineering Laboratory, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.
authors.forename: Harpreet Singh
authors.initials: HS
authors.lastname: Pawar
authors.affiliation: Biomaterials and Tissue Engineering Laboratory, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.
authors.forename: Bhuvaneshwaran
authors.initials: B
authors.lastname: Subramanian
authors.affiliation: Polymer Chemistry Laboratory, Department of Applied Chemistry, Indian School of Mines, Dhanbad 826004, India.
authors.forename: Sagar
authors.initials: S
authors.lastname: Pal
authors.affiliation: Biomaterials and Tissue Engineering Laboratory, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India. Electronic address: sdhara@smst.iitkgp.ernet.in.
authors.forename: Santanu
authors.initials: S
authors.lastname: Dhara
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology*; D001861:Bone Regeneration; D002234:Carbodiimides / Q000737:chemistry; D002454:Cell Differentiation; D048271:Chitosan / Q000737:chemistry*; D019343:Citric Acid / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry; D004548:Elasticity; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology; D061251:Primary Cell Culture; D011817:Rabbits; D013977:Tibia / Q000187:drug effects* / Q000293:injuries / Q000502:physiology / Q000601:surgery; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D002234:Carbodiimides; D003432:Cross-Linking Reagents; D019343:Citric Acid; D048271:Chitosan
keywords: Bone marrow derived mesenchymal stem cells; Dual cross-linking; Energy dissipation; Hydration effects; Interfacial phenomena; Osteogenesis