The promotion of bone regeneration by nanofibrous hydroxyapatite/chitosan scaffolds by effects on integrin-BMP/Smad signaling pathway in BMSCs
Abstract
In bone tissue engineering, a combination of biomimetic nanofibrous scaffolds with renewable stem cells has recently emerged as a new strategy for promoting bone regeneration. We have previously developed a biomimetic nanocomposite nanofibrous scaffold of hydroxyapatite/chitosan (nHAp/CTS) [1]. However, the mechanism behind the supportive function of the scaffolds has not yet been adequately explored. Here, we evaluated the effect of nHAp/CTS seeded with bone marrow mesenchymal stem cells (BMSCs) on bone regeneration and examined the underlying mechanism in vitro and in vivo. The scaffolds of nHAp/CTS induced higher proliferation of BMSCs than membranous hydroxyapatite/chitosan (mHAp/CTS) and electrospun nanofibrous chitosan (nCTS) did. Interestingly, regardless the nanfibrous effect, nHAp/CTS and mHAp/CTS supported the spindle-shaped morphology, in contrast to the spherical shape of BMSCs on nCTS, indicating that HAp supports cell adhesion. Furthermore, the levels of the mRNA for Smad1, BMP-2/4, Runx2, ALP, collagen I, integrin subunits together with myosins were significantly up-regulated on nHAp/CTS whereas these genes were expressed at markedly low levels on mHAp/CTS and nCTS even in osteogenic medium. In addition, the critical proteins pSmad1/5/8 in BMP pathway showed clear nuclear localization and osteocalcin were significantly elevated on nHAp/CTS than mHAp/CTS (P < 0.01) and nCTS (P < 0.01). Similarly, the cells exhibited higher ALP activity on nHAp/CTS than mHAp/CTS (P < 0.01) and nCTS (P < 0.05). Therefore, the findings indicated the activating of intergrin-BMP/Smad signaling pathway of BMSCs on nHAp/CTS. Finally, in vivo, nHAp/CTS/BMSCs had a superior ability of bone reconstruction than other groups for cranial bone defects. In conclusion, our results demonstrated that nHAp/CTS scaffold promotes bone regeneration by supporting the adhesion, proliferation and activating integrin-BMP/Smad signaling pathway of BMSCs both in vitro and in vivo.
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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 [65]
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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
- Authors
- Liu, H., Peng, H., Wu, Y., Zhang, C., Cai, Y., Xu, G., Li, Q., Chen, X., Ji, J., Zhang, Y., & OuYang, H. W.
- Affiliations
- Donghua University (CN)
- Zhejiang University (CN)
- First Affiliated Hospital Zhejiang University (CN)
- Corresponding author
- Zhang, Yanzhong
- OuYang, Hong Wei
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2013-06
- Volume
- 34
- Issue
- 18
- Pages
- 4404-4417
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2058774857
- Cited by
- 339
- References
- 51
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 25 · 2023: 23 · 2022: 18 · 2021: 23 · 2020: 25 · 2019: 27 · 2018: 25 · 2017: 41 · 2016: 35 · 2015: 28 · 2014: 37 · 2013: 7
- FWCI
- 19.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Physical Sciences › Materials Science › Biomaterials › Electrospun Nanofibers in Biomedical Applications
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- bone regeneration, bone marrow mesenchymal stem cells, Smad1/5/8, osteogenic differentiation, cell adhesion, cell proliferation, cranial bone defects
- MeSH terms
- Alkaline Phosphatase, Animals, Bone Marrow Cells, Bone Regeneration, Cell Separation, Extracellular Matrix, Female, Gene Expression Regulation, Membranes, Artificial, Osteogenesis, Radiography, Skull, Signal Transduction, Osteocalcin, Integrins, Rats, Sprague-Dawley, Durapatite, Bone Morphogenetic Proteins, Implants, Experimental, Chitosan, Cell Shape, Cell Proliferation, Rats, Smad Proteins, Tissue Scaffolds, Nanofibers, Mesenchymal Stem Cells
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