Acidic Osteoid Templates the Plywood Structure of Bone Tissue

Bone is created by osteoblasts that secrete osteoid after which an ordered texture emerges, followed by mineralization. Plywood geometries are a hallmark of many trabecular and cortical bones, yet the origin of this texturing in vivo has never been shown. Nevertheless, extensive in vitro work revealed how plywood textures of fibrils can emerge from acidic molecular cholesteric collagen mesophases. This study demonstrates in sheep, which is the preferred model for skeletal orthopaedic research, that the deeper non‐fibrillar osteoid is organized in a liquid‐crystal cholesteric geometry. This basophilic domain, rich in acidic glycosaminoglycans, exhibits low pH which presumably fosters mesoscale collagen molecule ordering in vivo. The results suggest that the collagen fibril motif of twisted plywood matures slowly through self‐assembly thermodynamically driven processes as proposed by the Bouligand theory of biological analogues of liquid crystals. Understanding the steps of collagen patterning in osteoid‐maturation processes may shed new light on bone pathologies that emerge from collagen physico‐chemical maturation imbalances. Extensive analyses of sheep bone biopsies ascertain that the deeper non‐fibrillar osteoid is organized in an acidic liquid‐crystal cholesteric geometry. Such acidic domains, most likely stabilized by glycosaminoglycans and citrate, foster collagen assembly from molecular into fibrillar plywood textures, a hallmark of many bone extracellular matrices. The results show that beyond cellular control, physicochemical thermodynamic processes drive bone maturation.