Article Rapid bone formation and remodeling via vascular infiltration of a hydroxyapatite/collagen nanocomposite beneath the calvarial periosteum

Hanae Arai ; Masayoshi Uezono ORCID ; Masanori Kikuchi SAMURAI ORCID ; Hitoshi Amano ; Chen Derong ORCID ; Kazuhiro Aoki ORCID ; Keiji Moriyama

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Hanae Arai, Masayoshi Uezono, Masanori Kikuchi, Hitoshi Amano, Chen Derong, Kazuhiro Aoki, Keiji Moriyama. Rapid bone formation and remodeling via vascular infiltration of a hydroxyapatite/collagen nanocomposite beneath the calvarial periosteum. Biomaterials and Biosystems. 2026, 21 (), 100130. https://doi.org/10.1016/j.bbiosy.2026.100130

Description:

(abstract)

This study investigated the time-dependent osteogenic potential of an organic-inorganic composite bone filler (hydroxyapatite/collagen bone-like nanocomposite, HAp/Col) using a rat calvarial model, assessed by immunohistochemistry and bone histomorphometry.
By day 3, vascular endothelial growth factor receptor 2 (VEGFR2)-positive cells were detected on the HAp/Col surface, indicating early vascular invasion. By day 5, vascular infiltration had extended into the scaffold, where double staining with tartrate resistant acid phosphatase (TRAP)/ alkaline phosphatase (ALP) revealed osteoclast-mediated material resorption and osteoblast-mediated bone matrix deposition around vascular cavities. By day 7, bone remodeling within HAp/Col was markedly active, with clusters of osteoblasts producing new bone matrix. Outside the scaffold, osteoblasts adhered to its surface and elongated, enhancing bone formation through the space-forming effect of HAp/Col swelling.
Furthermore, collagen triple helix repeat-containing protein 1 (CTHRC1) expression increased progressively from days 3 to 7, as confirmed by immunostaining and qRT-PCR, suggesting its role as a coupling factor between osteoclast activity and osteoblast differentiation.
These findings suggest that HAp/Col is associated with cellular activities related to bone remodeling, including vascular invasion and osteoclast/osteoblast recruitment. HAp/Col demonstrates biocompatibility and in vivo tissue compatibility as a candidate biomaterial for medical and dental applications.

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Keyword: Hydroxyapatite/collagen bone-like nanocomposite, Bone remodeling, Bone replacement, Osteoblast osteoclast angiogenesis, VEGF2R, CTHRC1

Date published: 2026-01-22

Publisher: Elsevier BV

Journal:

  • Biomaterials and Biosystems (ISSN: 26665344) vol. 21 100130

Funding:

  • Ministry of Education, Culture, Sports, Science and Technology (the establishment of university fellowship toward the creation of science technology innovation)
  • Japan Society for the Promotion of Science (JSPS) 21K17177a (KAKENHI Grant)

Manuscript type: Publisher's version (Version of record)

MDR DOI:

First published URL: https://doi.org/10.1016/j.bbiosy.2026.100130

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Updated at: 2026-02-21 16:30:04 +0900

Published on MDR: 2026-02-21 13:38:39 +0900

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