Biomimetic construction of oriented lamellar Col/nHAP composite scaffolds and mediation of macrophages to promote angiogenesis and bone regeneration

Abstract

Pore characteristics have been identified as key design parameters for osteoimmunomodulation. The strategy reported here is to create an appropriate immune microenvironment by regulating pore characteristics of scaffolds, thereby promoting early angiogenesis and enhancing osteogenesis. A series of collagen/nano-hydroxyapatite (Col/nHAP) composite scaffolds with ordered lamellar structures and different layer spacings were prepared by mimicking the ordered lamellar topology of the bone matrix. Our research indicated that the layer spacing and ordered topology of the scaffold exerted an important influence on phenotype transformation of macrophages and the secretion of angiogenic factors. The Col/nHAP-O(135) with large layer spacing not only supported cell attachment and diffusion in vitro, but also promoted early angiogenesis by timely switching from M1 to M2 macrophage phenotype. In vivo data showed that the layer spacing and the ordered structure of the scaffold synergistically regulated the inflammatory response and triggered macrophages to secrete more angiogenesis related cytokines. Col/nHAP-O(135) considerably promoted the neovascularization and new bone formation in the defect site, indicating that Col/nHAP-O(135) could significantly enhance the osteogenic activity of stem cells with the involvement of macrophages.

Graphical abstract

Keywords

pore characteristic / macrophage / vascularization / bone regeneration

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Authors’ contributions

Tingting Huang and Tao Huang carried out the preparation, characterization, cell experiment and animal experiment. The results were validated, analyzed and visualized by Tingting Huang, Di Xiao, and Pin Luo. Tingting Huang and Tao Huang wrote the original paper graft. Tingting Huang, Tao Huang, Pin Luo, Yiping Huang, Rong Zeng, and Mei Tu corrected and approved the paper draft. Mei Tu and Shenyu Yang provided the project resources.

Ethical statement

Animal experiments were approved by the Lab Animal Ethics Committee of Jinan University and the animals were housed in compliance with guiding principles for the care and use of animals.

Declaration of competing interests

The authors declare that they have no competing interests.

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 31971270) and the grant of Peak Climbing Project of Foshan Hospital of Traditional Chinese Medicine (CN) (No. 202000190).

Electronic supplementary information

Supplementary materials can be found in the online version at https://doi.org/10.1007/s11706-023-0666-4 and https://journal.hep.com.cn/foms/EN/10.1007/s11706-023-0666-4, which include Figs. S1 and S2.

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