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dc.contributor.authorAlakpa, Enateri Ven_UK
dc.contributor.authorBurgess, Karl E Ven_UK
dc.contributor.authorChung, Peteren_UK
dc.contributor.authorRiehle, Mathis Oen_UK
dc.contributor.authorGadegaard, Nikolajen_UK
dc.contributor.authorDalby, Matthew Johnen_UK
dc.contributor.authorCusack, Maggieen_UK
dc.description.abstractIt is counter-intuitive that invertebrate shells can induce bone formation yet nacre, or mother of pearl, from marine shells is both osteoinductive and osteointegrative. Nacre is composed of aragonite (calcium carbonate) and induces production of vertebrate bone (calcium phosphate). Exploited by the Mayans for dental implants, this remarkable phenomenon has been confirmed in vitro and in vivo yet the characteristic of nacre that induces bone formation remains unknown. By isolating nacre topography from its inherent chemistry in the production of polycaprolactone (PCL) nacre replica, we show that, for mesenchymal stem cells, nacre topography is osteoinductive. Gene expression of specific bone marker proteins, osteopontin, osteocalcin, osteonectin and osterix are increased 10-, 2- 1.7- and 1.8-fold respectively when compared to planar PCL. Furthermore, we demonstrate that bone tissue that forms in response to the physical topographical features of nacre has higher crystallinity than bone formed in response to chemical cues with full width half maximum for PO4 3- Raman shift of 7.6±0.7 for mineral produced in response to nacre replica compared to a much broader 34.6±10.1 in response to standard osteoinductive medium. These differences in mineral product are underpinned by differences in cellular metabolism. This observation can be exploited in the design of bone therapies; a matter that is most pressing in light of a rapidly ageing human population. Aragonite and calcite are the two calcium carbonate polymorphs that constitute the shell of molluscan bivalves conferring strength and resilience due to the nano- and microstructural assembly of the overall architecture. A small percentage of the invertebrate shell constitute the organic matrix which is responsible for the intricate processes of nucleation, growth and inhibition of calcium carbonate crystals resulting in the well-defined shell structure. The discovery of fully integrated shell dental implants in Mayan skulls initiated a number of studies showing that nacre, or mother of pearl, the aragonite calcium carbonate polymorph derived from the pearl oyster Pinctada maxima has good osteointegrative properties in vivo. Further exploration of this phenomenon in human jaw reconstructions and sheep femur implants confirm the osteointegrative properties of invertebrate shells. In addition, nacre initiates osteogenic differentiation in mesenchymal stem cells (MSCs) in vitro. This observation has led to a number of studies in which nacre and its chemistry have been incorporated into the design of existing biomaterials to induce bone formation. MSCs can be induced into undergoing osteogenesis in vitro by the use of pre-formulated soluble factors in the culture media, chemically defined surfaces, substrate matrix elasticity and the surface topography of the substrate. These approaches induce osteogenesis when presented in isolation or in combination. When these cues are presented in combination, surface patterning plays an important role and topography can have a stronger influence on cell behaviour when presented with effective surface chemistries. In vertebrate and invertebrate systems, the main requisites for forming hard tissue or biomineral structures are calcium phosphate and calcium carbonate respectively, both of which are assembled in a variety of ways generating an incredible amount of structural diversity. This juxtaposition of phosphate and carbonate is described as the “Bone-Shell Divide”. It is intriguing that mammalian cells respond to mineral on the shell side of the Bone-Shell Divide and this begs questions: which feature of nacre elicits this response and, in transcending the Bone-Shell Divide, do MSCs produce bone of similar or superior characteristics to that induced by other means? Addressing these questions has important implications in tissue engineering and biomaterial applications, especially with regards to orthopaedic applications where critical sized defects in trauma and reconstructive surgery demand large areas of intact bone usually acquired by creating a secondary injury site. By isolating the topographical features of nacre from its inherent chemistry, we show that the osteoinductive properties of nacre arise from the patterning of the surface presented to MSCs. Importantly, separating nacre topography from its inherent chemistry enhances the osteogenic response. In this report we dissect out the contribution of topography to nacre bioactivityen_UK
dc.publisherAmerican Chemical Societyen_UK
dc.relationAlakpa EV, Burgess KEV, Chung P, Riehle MO, Gadegaard N, Dalby MJ & Cusack M (2017) Nacre Topography Produces Higher Crystallinity in Bone than Chemically Induced Osteogenesis, ACS Nano, 11 (7), pp. 6717-6727.
dc.rightsThis is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.en_UK
dc.titleNacre Topography Produces Higher Crystallinity in Bone than Chemically Induced Osteogenesisen_UK
dc.typeJournal Articleen_UK
dc.citation.jtitleACS nanoen_UK
dc.type.statusVoR - Version of Recorden_UK
dc.contributor.funderMedical Research Councilen_UK
dc.contributor.affiliationUniversity of Glasgowen_UK
dc.contributor.affiliationUniversity of Glasgowen_UK
dc.contributor.affiliationUniversity of Glasgowen_UK
dc.contributor.affiliationInstitute of Molecular and Cell Biology - A*STARen_UK
dc.contributor.affiliationUniversity of Glasgowen_UK
dc.contributor.affiliationUniversity of Glasgowen_UK
dc.contributor.affiliationBiological and Environmental Sciencesen_UK
dc.description.refREF Compliant by Deposit in Stirling's Repositoryen_UK
Appears in Collections:Biological and Environmental Sciences Journal Articles

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