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Int. J. Mol. Sci. 2018, 19(2), 427; https://doi.org/10.3390/ijms19020427

Amorphous, Smart, and Bioinspired Polyphosphate Nano/Microparticles: A Biomaterial for Regeneration and Repair of Osteo-Articular Impairments In-Situ

1
ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Duesbergweg 6, 55128 Mainz, Germany
2
Institute of Functional and Clinical Anatomy, University Medical Center of the Johannes Gutenberg University Mainz, Johann Joachim Becher Weg 13, 55099 Mainz, Germany
3
Institute of Materials Science (ICMUV), Universitat de València, C/Catedràtic José Beltrán 2, Paterna, 46980 València, Spain
4
Key Laboratory of Advanced Materials of Ministry of Education of China, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China
*
Authors to whom correspondence should be addressed.
Received: 23 November 2017 / Revised: 27 January 2018 / Accepted: 29 January 2018 / Published: 31 January 2018
(This article belongs to the Collection Bioactive Nanoparticles)
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Abstract

Using femur explants from mice as an in vitro model, we investigated the effect of the physiological polymer, inorganic polyphosphate (polyP), on differentiation of the cells of the bone marrow in their natural microenvironment into the osteogenic and chondrogenic lineages. In the form of amorphous Ca-polyP nano/microparticles, polyP retains its function to act as both an intra- and extracellular metabolic fuel and a stimulus eliciting morphogenetic signals. The method for synthesis of the nano/microparticles with the polyanionic polyP also allowed the fabrication of hybrid particles with the bisphosphonate zoledronic acid, a drug used in therapy of bone metastases in cancer patients. The results revealed that the amorphous Ca-polyP particles promote the growth/viability of mesenchymal stem cells, as well as the osteogenic and chondrogenic differentiation of the bone marrow cells in rat femur explants, as revealed by an upregulation of the expression of the transcription factors SOX9 (differentiation towards osteoblasts) and RUNX2 (chondrocyte differentiation). In parallel to this bone anabolic effect, incubation of the femur explants with these particles significantly reduced the expression of the gene encoding the osteoclast bone-catabolic enzyme, cathepsin-K, while the expression of the tartrate-resistant acid phosphatase remained unaffected. The gene expression data were supported by the finding of an increased mineralization of the cells in the femur explants in response to the Ca-polyP particles. Finally, we show that the hybrid particles of polyP complexed with zoledronic acid exhibit both the cytotoxic effect of the bisphosphonate and the morphogenetic and mineralization inducing activity of polyP. Our results suggest that the Ca-polyP nano/microparticles are not only a promising scaffold material for repairing long bone osteo-articular damages but can also be applied, as a hybrid with zoledronic acid, as a drug delivery system for treatment of bone metastases. The polyP particles are highlighted as genuine, smart, bioinspired nano/micro biomaterials. View Full-Text
Keywords: long bone defects; bone marrow cells; inorganic polyphosphate; microparticles; bisphosphonates; Runx2; Sox9; cathepsin-K; tumor metastases; human mesenchymal stem cells long bone defects; bone marrow cells; inorganic polyphosphate; microparticles; bisphosphonates; Runx2; Sox9; cathepsin-K; tumor metastases; human mesenchymal stem cells
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Müller, W.E.G.; Neufurth, M.; Wang, S.; Ackermann, M.; Muñoz-Espí, R.; Feng, Q.; Lu, Q.; Schröder, H.C.; Wang, X. Amorphous, Smart, and Bioinspired Polyphosphate Nano/Microparticles: A Biomaterial for Regeneration and Repair of Osteo-Articular Impairments In-Situ. Int. J. Mol. Sci. 2018, 19, 427.

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