RALA complexed α-TCP nanoparticle delivery to mesenchymal stem cells induces bone formation in tissue engineered constructs in vitro and in vivo

Binnulal Sathy, Dinorath Olvera, Tomas Gonzalez-Fernandez, Gráinne M. Cunniffe, Sreekanth Pentlavalli, Philip Chambers, Oju Jeon, Eben Alsberg, Helen O. McCarthy, Nicholas Dunne, Tammy L Haut Donahue, Daniel J Kelly

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9 Citations (Scopus)

Abstract

A range of bone regeneration strategies, from growth factor delivery and/or mesenchymal stem cell (MSC) transplantation to endochondral tissue engineering, have been developed in recent years. Despite their tremendous promise, the clinical translation and future use of many of these strategies is being hampered by concerns such as off target effects associated with growth factor delivery. Therefore the overall objective of this study was to investigate the influence of alpha-tricalcium phosphate (α-TCP) nanoparticle delivery into MSCs using an amphipathic cell penetrating peptide RALA, on osteogenesis in vitro and both intramembranous and endochondral bone formation in vivo. RALA complexed α-TCP nanoparticle delivery to MSCs resulted in an increased expression of bone morphogenetic protein-2 (BMP-2) and an upregulation in a number of key osteogenic genes. When α-TCP stimulated MSCs were encapsulated into alginate hydrogels, enhanced mineralization of the engineered construct was observed over a 28 day culture period. Furthermore, the in vivo bone forming potential of RALA complexed α-TCP nanoparticle delivery to MSCs was found to be comparable to growth factor delivery. Recognizing the potential and limitations associated with endochondral bone tissue engineering strategies, we then sought to explore how α-TCP nanoparticle delivery to MSCs influences early mineralization of engineered cartilage templates in vitro and their subsequent ossification in vivo. Despite accelerating mineralization of engineered cartilage templates in vitro, RALA complexed α-TCP nanoparticle delivery did not enhance endochondral bone formation in vivo. Therefore the potential of RALA complexed α-TCP nanoparticle delivery appears to be as an alternative to growth factor delivery as a single stage strategy for promoting bone generation.
Original languageEnglish
Pages (from-to)1753-1764
Number of pages11
JournalJournal of Materials Chemistry B
Volume5
Issue number9
Early online date12 Jan 2017
DOIs
Publication statusPublished - Mar 2017

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    Sathy, B., Olvera, D., Gonzalez-Fernandez, T., Cunniffe, G. M., Pentlavalli, S., Chambers, P., Jeon, O., Alsberg, E., McCarthy, H. O., Dunne, N., Haut Donahue, T. L., & Kelly, D. J. (2017). RALA complexed α-TCP nanoparticle delivery to mesenchymal stem cells induces bone formation in tissue engineered constructs in vitro and in vivo. Journal of Materials Chemistry B, 5(9), 1753-1764. https://doi.org/10.1039/C6TB02881K