Enhanced osteogenesis through nano-structured surface design of macroporous hydroxyapatite bioceramic scaffolds via activation of ERK and p38 MAPK signaling pathways
Abstract
The design of the three-dimensional (3D) porous structures and surface morphological/topographies of implants is considered as a novel approach to enhance the bioactivity and osteoinductive ability in the field of bone regeneration. In the present study, highly interconnective macroporous hydroxyapatite (HAp) bioceramic scaffolds with nanosheet, nanorod and micro-nano-hybrid (the hybrid of nanorod and microrod) surface topographies were fabricated using α-tricalcium phosphate (α-TCP) ceramic scaffolds as precursors, through regulation of the hydrothermal reaction conditions. Moreover, the effects of these three surface topographies on attachment, proliferation and osteogenic differentiation of rat bone marrow stromal cells (bMSCs) as well as the related mechanisms were systematically investigated. The results showed that the HAp bioceramics with these micro-/nano-topography surfaces significantly enhanced cell attachment, cell viability, alkaline phosphatase (ALP) activity, and mRNA expression levels of osteoblast-related genes of bMSCs. In particular, the biomimetic feature of the micro-nano-hybrid topography surface possessed the highest stimulatory effect. The activation in extracellular signal-related kinases (ERK), and p38 mitogen-activated protein kinase (MAPK) signaling pathways was observed in bMSCs cultured on HAp bioceramics with micro-/nano-topography surfaces especially for the micro-nano-hybrid topography surface, and these enhancement effects could be blocked by ERK inhibitor PD98059, and P38 inhibitor SB203580, respectively. Moreover, the in vivo bone regeneration results of rat critical-sized calvarial defect models confirmed that macroporous HAp bioceramics with these micro-/nano-topography surfaces could promote new bone formation and mineralization as compared with the control HAp bioceramic with traditional smooth surfaces, while the scaffold with a micro-nano-hybrid surface could achieve a better effect. The study suggests that the hierarchical micro-nano-hybrid topography shows immense potential in improving the clinical performance of macroporous HAp bioceramics.
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Hydroxyapatite can interact with bone marrow mesenchymal stem cells and enhance BMSC proliferation, differentiation, and mineralization through signaling pathways including ERK/Sox9, BMP/Smad, Wnt/beta-catenin, TGF-beta, and MAPK.
“Hydroxyapatite, a natural apatite mineral, has the capacity to interact with bone marrow mesenchymal stem cells (BMSCs) and enhance BMSC proliferation, differentiation, and mineralization through its action on various signaling pathways, including ERK/Sox9, BMP/Smad, Wnt/β-catenin, TGF-β, and MAPK [64,65,66,67,68].”
From Recent Advances in Silk Fibroin-Based Composites for Bone Repair Applications: A Review (2025) · cites this paper as [68]
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Qian, Y., Zhou, X., Zhang, F., Diekwisch, T. G. H., Luan, X., & Yang, J. (2019) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.9b07053 · Cited by 235 · see citing works
Recent Advances in Silk Fibroin-Based Composites for Bone Repair Applications: A Review
Zhu, S., Zhang, Q., Xu, X., Liu, Z., Cheng, G., Long, D., Cheng, L., & Dai, F. (2025) · Polymers · doi:10.3390/polym17060772 · Cited by 36 · see citing works
“…a natural apatite mineral, has the capacity to interact with bone marrow mesenchymal stem cells (BMSCs) and enhance BMSC proliferation, differentiation, and mineralization through its action on various signaling pathways, including ERK/Sox9, BMP/Smad, Wnt/ β -catenin, TGF-β , and MAPK [64–68].”
- Authors
- Xia, L., Lin, K., Jiang, X., Xu, Y., Zhang, M., Chang, J., & Zhang, Z.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Chang, Jiang
- Zhang, Zhiyuan
- Venue
- Journal of Materials Chemistry B
- Publisher
- Royal Society of Chemistry (RSC)
- Published
- 2013
- Volume
- 1
- Issue
- 40
- Pages
- 5403
- ISSN
- 2050-750X (ISSN-L)
- 2050-7518
- OpenAlex
- W2012412040
- Cited by
- 146
- References
- 55
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 5 · 2023: 9 · 2022: 15 · 2021: 7 · 2020: 23 · 2019: 14 · 2018: 13 · 2017: 19 · 2016: 13 · 2015: 7 · 2014: 8 · 2013: 1
- FWCI
- 5.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Materials Chemistry B (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Vanderbilt University
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Physical Sciences › Engineering › Mechanical Engineering › Surface Treatment and Coatings
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- macroporous scaffolds, surface topography, osteogenic differentiation, mesenchymal stem cells, ERK signaling, p38 MAPK signaling pathway, bone regeneration, critical-size calvarial defect, alkaline phosphatase activity, hierarchical surface morphology, hydrothermal synthesis
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