Self-Assembled Collagen-Apatite Composite Biomaterial as Injectable Biomimetic Substitute for Tissue Repair

In human biological tissue, type I collagen, the main structural protein, forms dense anisotropic structures with ordered geometries. Given that collagen exhibits liquid-crystal properties <i>in vitro</i> [1], it was suggested that the molecules might share such properties <i>in vivo</i> [2], potentially explaining these 3D arrangements. Consequently, tissue mineralization could be partly driven by collagen self-assembly and subsequent fibrillar confinement, allowing the co-alignment of collagen fibrils and apatite platelets [3].<br/>This work aims to present a bioinspired and innovative synthesis to elaborate an injectable biomaterial. The organic/inorganic ratio of the tissue-like composite can be adjusted to match the composition of specific natural mineralized tissues, and liquid-crystal properties of collagen molecules are leveraged to replicate its complex microstructure accurately. The organic component consists of spray-dried, non-denatured collagen microparticles. Although type I collagen is highly viscous and hardly injectable above 10 mg/mL, these dense, non-denatured particles allow the formation of highly concentrated gels by injection when mixed with an aqueous solvent and the mineral part, composed by biomimetic hydroxyapatite nanocrystals. Upon injection, the concentration required for the self-assembly of collagen molecules into liquid crystal phases is easily reached (above 40 mg/mL), a sine qua non condition to mimic the ultrastructure of biological tissues [4].<br/>We show that our bioinspired process preserves collagen self-assembly properties and enhances fibril formation without any additional synthesis step. Moreover, the addition of biomimetic hydroxyapatite particles leads to tissue-like features with the presence of domains where collagen and apatite co-align. Furthermore, our characterizations and <i>in vivo</i> results demonstrate that these biomimetic materials are biocompatible and promising for various tissue repair applications.<br/>The synthesis of a dense collagen/apatite material through a self-assembly step represents a versatile tool to form mineralized matrices with tissue-like features as well as for repairing any type of material with a minimally invasive technique. This straightforward procedure provides also a model to study the physico-chemical mechanisms involved in tissue mineralization.<br/>References:<br/>[1] M.M. Giraud-Guille, L. Besseau, Connect. Tissue Res. (1998) 37(3-4), 183-193<br/>[2] R. Martin <i>et al</i>., J. Mol. Biol. (2000) 301(1), 11-17<br/>[3] Y. Wang, <i>et al.</i>, Nat. Mater. (2012) 11, 724–733.<br/>[4] M.M. Giraud Guille, N. Nassif, F. M. Fernandes, in Materials Design Inspired by Nature: Function Through Inner Architecture, ed. P. Fratzl, J. Dunlop, and R. Weinkamer, RSC (2013), 107-127.