Lamellar bone,compactly and ingeniously organized in the hierarchical pattern with 6 ordered scales,is the structural motif of mature bone.Each hierarchical scale exerts an essential role in determining physiological ...Lamellar bone,compactly and ingeniously organized in the hierarchical pattern with 6 ordered scales,is the structural motif of mature bone.Each hierarchical scale exerts an essential role in determining physiological behavior and osteogenic bioactivity of bone.Engineering lamellar bone with full-scale hierarchy remains a longstanding challenge.Herein,using bioskiving and mineralization,we attempt to engineer compact constructs resembling full-scale hierarchy of lamellar bone.Through systematically investigating the effect of mineralization on physicochemical properties and bioactivities of multi-sheeted collagen matrix fabricated by bioskiving,the hierarchical mimicry and hierarchy-property relationship are elucidated.With prolongation of mineralization,hierarchical mimicry and osteogenic bioactivity of constructs are performed in a bidirectional manner,i.e.first rising and then descending,which is supposed to be related with transformation of mineralization mechanism from nonclassical to classical crystallization.Construct mineralized 9 days can accurately mimic each hierarchical scale and efficiently promote osteogenesis.Bioinformatic analysis further reveals that this construct potently activates integrinα5-PI3K/AKT signaling pathway through mechanical and biophysical cues,and thereby repairing critical-sized bone defect.The present study provides a bioinspired strategy for completely resembling complex hierarchy of compact mineralized tissue,and offers a critical research model for in-depth studying the structure-function relationship of bone.展开更多
基金funded by National Natural Science Foundation of China(Grant No.82001094 and 21905094)Guangzhou Science and Technology Program(Grant No.202102020519 and 202201010912)+2 种基金Guangdong Financial Fund for High-Caliber Hospital Construction(Grant No.174-2018-XMZC-0001-03-0125/D-20)Open Funding of Guangdong Provincial Key Laboratory of Stomatology(No.KF2022120104)Guangdong Basic and Applied Basic Research Foundation(Grant No.2019A1515110379 and 2021A1515010782).
文摘Lamellar bone,compactly and ingeniously organized in the hierarchical pattern with 6 ordered scales,is the structural motif of mature bone.Each hierarchical scale exerts an essential role in determining physiological behavior and osteogenic bioactivity of bone.Engineering lamellar bone with full-scale hierarchy remains a longstanding challenge.Herein,using bioskiving and mineralization,we attempt to engineer compact constructs resembling full-scale hierarchy of lamellar bone.Through systematically investigating the effect of mineralization on physicochemical properties and bioactivities of multi-sheeted collagen matrix fabricated by bioskiving,the hierarchical mimicry and hierarchy-property relationship are elucidated.With prolongation of mineralization,hierarchical mimicry and osteogenic bioactivity of constructs are performed in a bidirectional manner,i.e.first rising and then descending,which is supposed to be related with transformation of mineralization mechanism from nonclassical to classical crystallization.Construct mineralized 9 days can accurately mimic each hierarchical scale and efficiently promote osteogenesis.Bioinformatic analysis further reveals that this construct potently activates integrinα5-PI3K/AKT signaling pathway through mechanical and biophysical cues,and thereby repairing critical-sized bone defect.The present study provides a bioinspired strategy for completely resembling complex hierarchy of compact mineralized tissue,and offers a critical research model for in-depth studying the structure-function relationship of bone.
