Bioactive Materials (Sep 2023)

An engineered lamellar bone mimicking full-scale hierarchical architecture for bone regeneration

  • Tao Yang,
  • Zhichao Hao,
  • Zhenzhen Wu,
  • Binxin Xu,
  • Jiangchen Liu,
  • Le Fan,
  • Qinmei Wang,
  • Yanshan Li,
  • Dongying Li,
  • Sangzhu Tang,
  • Chuanzi Liu,
  • Weichang Li,
  • Wei Teng

Journal volume & issue
Vol. 27
pp. 181 – 199

Abstract

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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 integrin α5-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.

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