title: Synthesis of bone-like nanocomposites using multiphosphorylated peptides.
abstract: There is a great need for novel materials for mineralized tissue repair and regeneration. Two examples of such tissue, bone and dentin, are highly organized hierarchical nanocomposites in which mineral and organic phases interface at the molecular level. In contrast, current graft materials are either ceramic powders or physical blends of mineral and organic phases with mechanical properties far inferior to those of their target tissues. The objective of this study was to synthesize composite nanofibrils with highly integrated organic/inorganic phases inspired by the mineralized collagen fibrils of bone and dentin. Utilizing our understanding of bone and dentin biomineralization, we have first designed bioinspired peptides containing 3 Ser-Ser-Asp repeat motifs based on the highly phosphorylated protein, dentin phosphophoryn (DPP), found in dentin and alveolar bone. We demonstrate that up to 80% of serines in the peptide can be phosphorylated by casein kinases. We further tested the ability of these peptides to induce biomimetic calcium phosphate mineralization of collagen fibrils. Our mineralization studies have revealed that in the presence of these phosphorylated peptides, mineralized collagen fibrils structurally similar to the mineralized collagen fibrils of bone and dentin were formed. Our results demonstrate that using phosphorylated DPP-inspired peptides, we can successfully synthesize biomimetic composite nanofibrils with integrated organic and inorganic phases. These results provide the first step in the development of biomimetic nanostructured materials for mineralized tissue repair and regeneration using phosphopeptides.
authors.affiliation: University of Pittsburgh, School of Dental Medicine, McGowan Institute of Regenerative Medicine, Center for Craniofacial Regeneration, 552 Salk Hall, 3501 Terrace St., Pittsburgh, PA 15261, USA. Electronic address: csfeir@pitt.edu.
authors.forename: Charles
authors.initials: C
authors.lastname: Sfeir
authors.affiliation: Department of Oral Biology, School of Dental Medicine and the Center for Craniofacial Regeneration, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Ping-An
authors.initials: PA
authors.lastname: Fang
authors.affiliation: Department of Oral Biology, School of Dental Medicine and the Center for Craniofacial Regeneration, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Thottala
authors.initials: T
authors.lastname: Jayaraman
authors.affiliation: Department of Oral Biology, School of Dental Medicine and the Center for Craniofacial Regeneration, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Aparna
authors.initials: A
authors.lastname: Raman
authors.affiliation: Department of Oral Biology, School of Dental Medicine and the Center for Craniofacial Regeneration, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Xiaoyuan
authors.affiliation: University of Pittsburgh, School of Dental Medicine, McGowan Institute of Regenerative Medicine, Center for Craniofacial Regeneration, 552 Salk Hall, 3501 Terrace St., Pittsburgh, PA 15261, USA. Electronic address: ebeniash@pitt.edu.
authors.forename: Elia
authors.initials: E
authors.lastname: Beniash
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D002113:Calcification, Physiologic; D047388:Casein Kinases / Q000378:metabolism; D004583:Electrons; D024022:Fibrillar Collagens / Q000378:metabolism; D007700:Kinetics; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D053761:Nanocomposites / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D014054:Tomography
chemical_list: D024022:Fibrillar Collagens; D010455:Peptides; D000255:Adenosine Triphosphate; D047388:Casein Kinases
keywords: Bioinspired; Bone; Mineralized tissue; Regeneration