Nacre Topography Produces Higher Crystallinity in Bone than Chemically Induced Osteogenesis

It is counterintuitive 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, is 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 a higher crystallinity than bone formed in response to chemical cues with a full width half-maximum for Po-4(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 aging human population.