Mineral Formation in Twisted Plywood Structures

Many biological tissues exhibit fibrillar organizations known as twisted plywood or helicoid. This arrangement is similar to that of molecules in cholesteric liquid crystalline phases, though the liquid character is abolished (1). Cholesteric and other liquid crystalline-like organizations are encountered in various extracellular matrices composed of different components, especially collagen, chitin, cellulose and DNA. This structural analogy between living tissues and liquid crystals emphasizes the importance of the structure-properties relationship in biological tissues and suggests similar self-assembly mechanisms in both systems as recently shown in bone (2).<br/> The twisted plywood structure of mineralized collagen fibrils is a hallmark of trabecular and cortical bones, and our team's work aims to demonstrate the importance of reproducing this structure in terms of composition and structure. Collagen fibril order induces the formation of restrictive gaps allowing for the supersaturation of molecules (proteins, ions) and the establishment of unconventional thermodynamic conditions. Indeed, proteins can exhibit opposite activities depending on their surrounding state, whether in diluted or condensed conditions (3), which might have significant implications on mineral formation.<br/> Our team work aims to enhance our understanding of fundamental questions in morphogenesis and to develop competitive biomaterials. We use the lyotropic properties of Type I collagen, the major structural protein of connective tissue. The phase diagram of collagen molecules, in acid solution at high concentration exhibits successively nematic, precholesteric* (4)/precholesteric, and cholesteric phases (5). After a sol/gel transition, collagen fibrils form while preserving the cholesteric geometry (6). The materials were successfully scaled up (from drop to 3D bulk material) using a bioinspired process based on the continuous injection of collagen, mimicking protein secretion by cells (7). In parallel, we set an apatite mineralization process that led to synthetic platelets whose structure and behavior in water mimic those of biological apatite (8). Combining these processes leads to build collagen/apatite composites with high similarity to bone tissue (9). In vitro and in vivo investigations were also performed to control their cyto- and biocompatibility and to evaluate their potential for bone repair (10, 11).<br/> We will show that reproducing this bone building block provides efficient models to study fundamental questions on tissue morphogenesis and, more particularly, bone biomineralization. This approach also serves as a strong starting point for applications in bone tissue engineering through the design of new implantable materials, as autologous bone is still considered the gold standard. Overall, it shows the importance of physico-chemical processes occurring in biomineralization, as usually discussed from a biological control point of view.<br/> <br/>(1) Y. Bouligand, Tissue Cell. 4, 189–217 (1972).<br/>(2) M. Robin, <i>et al.</i> Adv. Sci. 11 (9), 2304454 (2024).<br/>(3) G.K. Hunter, H.A. Goldberg, Proc. Natl. Acad. Sci. USA. 90, 8562-8565 (1993).<br/>(4) C. Salameh, F. Salviat, Proc. Natl. Acad. Sci. USA. 117(22), 11947-11953 (2020).<br/>(5) L. Besseau, M.M. Giraud-Guille. Connect. Tissue Res. 37, 183-193 (1998).<br/>(6) L. Besseau, M.M. Giraud-Guille. J. Mol. Biol. 251, 197–202 (1995).<br/>(7) Y. Wang, <i>et al.</i> Soft matter. 7, 9659−9664 (2011).<br/>(8) Y. Wang, S. Von Euw, <i>et al.</i> Nat. Mater. 12 (12), 1144-1153 (2013).<br/>(9) Y. Wang, <i>et al.</i> Nat Mater. 11, 724–733 (2012).<br/>(10) M. Robin, <i>et al.</i> Bone. 88, 146-156 (2016).<br/>(11) M. Robin, <i>et al.</i> under review.<br/>(12) S. Ghazanfari, <i>et al.</i> Biomaterials. 97, 74 (2016).