The Hydrophilic Amorphous Layer Around Bone Apatite Promotes Osteogenesis

Bone tissue can be regarded as a nanocomposite material primarily built from an organic collagenous matrix reinforced with inorganic apatite nanoparticles¹. The function of bone apatite nanoparticles does not, however, simply boil down to mechanical reinforcement. There is growing appreciation that they are pivotal factors in the mechanisms underlying bone remodelling² and bone metastasis³, while they are also affected by certain metabolic bone diseases⁴. In this regard, biomaterial-based therapies aimed at regenerating damaged or diseased bones have long been using different forms of synthetic calcium phosphate particles to improve their overall performance⁵. However, from pre-clinical testing at the laboratory scale to clinical solutions, the aforementioned therapies are based on synthetic analogues that are often not biologically relevant as they tend to disregard the intricate complexity of biogenic calcium phosphates^6–9, especially the fact that the composition, structure and other physicochemical characteristics of calcium phosphate particles in bone are heterogeneous in space and time¹⁰. Using a series of synthetic organic–inorganic nanocomposite materials containing well-defined proxies for biogenic calcium phosphate particles at the different stages of bone biomineralization, we show that human mesenchymal stem/stromal cells (hMSCs) osteogenesis is substantially enhanced when a hydrophilic amorphous layer is present at the surface of the calcium phosphate particles. This hydrophilic amorphous surface layer is naturally occurring around bone apatite nanoparticles⁶ and, hence, may contribute to the so far unrivalled performance of autologous bone grafting procedures. These results offer a previously unexplored perspective around intrinsic osteoinductive properties and emphasize the critical importance of truly biomimetic designs for developing competitive biomaterials for bone healing. They also open new avenues to uncover the extent to which this hydrophilic amorphous surface layer may also regulate the behaviour of other types of cells and, in turn, influences a number of key bone physiological and pathological processes.<br/><br/><b>References:</b><br/>1. N. Reznikov, M. Bilton, L. Lari, M. M. Stevens, R. Kröger, <i>Science</i>. <b>360</b>, eaao2189 (2018).<br/>2. M. Robin, C. Almeida, T. Azaïs, B. Haye, C. Illoul, J. Lesieur, M.-M. Giraud-Guille, N. Nassif, C. Hélary, <i>Bone</i>. <b>88</b>, 146–156 (2016).<br/>3. F. He, A. E. Chiou, H. C. Loh, M. Lynch, B. R. Seo, Y. H. Song, M. J. Lee, R. Hoerth, E. L. Bortel, B. M. Willie, G. N. Duda, L. A. Estroff, A. Masic, W. Wagermaier, P. Fratzl, C. Fischbach, <i>Proc. Natl. Acad. Sci.</i> <b>114</b>, 10542–10547 (2017).<br/>4. P. Zeng, Y. Fu, Y. Pang, T. He, Y. Wu, R. Tang, A. Qin, X. Kong, <i>ACS Biomater. Sci. Eng.</i> <b>7</b>, 1159–1168 (2021).<br/>5. R. Z. LeGeros, <i>Clin. Orthop. Relat. Res.</i> <b>395</b> (2002) (available at https://journals.lww.com/clinorthop/Fulltext/2002/02000/Properties_of_Osteoconductive_Biomaterials_.9.aspx).<br/>6. Y. Wang, S. Von Euw, F. M. Fernandes, S. Cassaignon, M. Selmane, G. Laurent, G. Pehau-Arnaudet, C. Coelho, L. Bonhomme-Coury, M.-M. Giraud-Guille, F. Babonneau, T. Azaïs, N. Nassif, <i>Nat. Mater.</i> <b>12</b>, 1144–1153 (2013).<br/>7. K. A. DeRocher, P. J. M. Smeets, B. H. Goodge, M. J. Zachman, P. V. Balachandran, L. Stegbauer, M. J. Cohen, L. M. Gordon, J. M. Rondinelli, L. F. Kourkoutis, D. Joester, <i>Nature</i>. <b>583</b>, 66–71 (2020).<br/>8. L. M. Gordon, M. J. Cohen, K. W. MacRenaris, J. D. Pasteris, T. Seda, D. Joester, <i>Science</i>. <b>347</b>, 746–750 (2015).<br/>9. G. Cho, Y. Wu, J. L. Ackerman, <i>Science</i>. <b>300</b>, 1123–1127 (2003).<br/>10. M. J. Glimcher, <i>Rev. Mineral. Geochem.</i> <b>64</b>, 223–282 (2006).