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Nucleation and growth of mineralized bone matrix on silk-hydroxyapatite composite scaffolds
Open accessAbstract
We describe a composite hydroxyapatite (HA)-silk fibroin scaffold designed to induce and support the formation of mineralized bone matrix by human mesenchymal stem cells (hMSCs) in the absence of osteogenic growth factors. Porous three-dimensional silk scaffolds were extensively used in our previous work for bone tissue engineering and showed excellent biodegradability and biocompatibility. However, silk is not an osteogenic material and has a compressive stiffness significantly lower than that of native bone. In the present study, we explored the incorporation of silk sponge matrices with HA (bone mineral) micro-particles to generate highly osteogenic composite scaffolds capable of inducing the in vitro formation of tissue-engineered bone. Different amounts of HA were embedded in silk sponges at volume fractions of 0%, 1.6%, 3.1% and 4.6% to enhance the osteoconductive activity and mechanical properties of the scaffolds. The cultivation of hMSCs in the silk/HA composite scaffolds under perfusion conditions resulted in the formation of bone-like structures and an increase in the equilibrium Young's modulus (up to 4-fold or 8-fold over 5 or 10 weeks of cultivation, respectively) in a manner that correlated with the initial HA content. The enhancement in mechanical properties was associated with the development of the structural connectivity of engineered bone matrix. Collectively, the data suggest two mechanisms by which the incorporated HA enhanced the formation of tissue engineered bone: through osteoconductivity of the material leading to increased bone matrix production, and by providing nucleation sites for new mineral resulting in the connectivity of trabecular-like architecture.
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“Compared with the uncombined silk fibroin scaffold, the composite porous fibroin scaffold can form more bone tissue faster.”
From Recent Advances in Silk Fibroin-Based Composites for Bone Repair Applications: A Review (2025) · cites this paper as [70]
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Metadata
- Authors
- Bhumiratana, S., Grayson, W. L., Castaneda, A., Rockwood, D. N., Gil, E. S., Kaplan, D. L., & Vunjak-Novakovic, G.
- Affiliations
- Columbia University (US)
- Johns Hopkins University (US)
- Tufts University (US)
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 32
- Issue
- 11
- Pages
- 2812-2820
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC3042545
- OpenAlex
- W2020617826
- Cited by
- 265
- References
- 41
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 15 · 2023: 9 · 2022: 12 · 2021: 9 · 2020: 15 · 2019: 16 · 2018: 18 · 2017: 23 · 2016: 30 · 2015: 25 · 2014: 24 · 2013: 32 · 2012: 18
- FWCI
- 15.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Biomedical Imaging and Bioengineering (EB 003210, R01EB003210, P41EB002520)
- National Institute of Dental and Craniofacial Research (DE-016525, R01DE016525)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Physical Sciences › Materials Science › Biomaterials › Silk-based biomaterials and applications
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- silk fibroin, hydroxyapatite, composite scaffolds, bone tissue engineering, human mesenchymal stem cells, osteoconductivity, mineral nucleation, scaffold mechanical properties, Young's modulus, trabecular bone microarchitecture, perfusion bioreactor
- MeSH terms
- Calcification, Physiologic, Cell Survival, Cells, Cultured, Humans, Immunohistochemistry, Microscopy, Electron, Scanning, Durapatite, Tissue Engineering, Silk, Tissue Scaffolds, Mesenchymal Stem Cells
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