An instantly fixable and self-adaptive scaffold for skull regeneration by autologous stem cell recruitment and angiogenesis

Gonggong Lu, Yang Xu, Quanying Liu, Manyu Chen, Huan Sun, Peilei Wang, Xing Li, Yuxiang Wang, Xiang Li, Xuhui Hui, En Luo, Jun Liu, Qing Jiang, Jie Liang, Yujiang Fan (), Yong Sun () and Xingdong Zhang
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Gonggong Lu: Sichuan University
Yang Xu: Sichuan University
Quanying Liu: Sichuan University
Manyu Chen: Sichuan University
Huan Sun: Sichuan University
Peilei Wang: Sichuan University
Xing Li: Sichuan University
Yuxiang Wang: Sichuan University
Xiang Li: Sichuan University
Xuhui Hui: Sichuan University
En Luo: Sichuan University
Jun Liu: Southeast University
Qing Jiang: Sichuan University
Jie Liang: Sichuan University
Yujiang Fan: Sichuan University
Yong Sun: Sichuan University
Xingdong Zhang: Sichuan University

Nature Communications, 2022, vol. 13, issue 1, 1-20

Abstract: Abstract Limited stem cells, poor stretchability and mismatched interface fusion have plagued the reconstruction of cranial defects by cell-free scaffolds. Here, we designed an instantly fixable and self-adaptive scaffold by dopamine-modified hyaluronic acid chelating Ca2+ of the microhydroxyapatite surface and bonding type I collagen to highly simulate the natural bony matrix. It presents a good mechanical match and interface integration by appropriate calcium chelation, and responds to external stress by flexible deformation. Meanwhile, the appropriate matrix microenvironment regulates macrophage M2 polarization and recruits endogenous stem cells. This scaffold promotes the proliferation and osteogenic differentiation of BMSCs in vitro, as well as significant ectopic mineralization and angiogenesis. Transcriptome analysis confirmed the upregulation of relevant genes and signalling pathways was associated with M2 macrophage activation, endogenous stem cell recruitment, angiogenesis and osteogenesis. Together, the scaffold realized 97 and 72% bone cover areas after 12 weeks in cranial defect models of rabbit (Φ = 9 mm) and beagle dog (Φ = 15 mm), respectively.

Date: 2022
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DOI: 10.1038/s41467-022-30243-5

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