Osteoinduction and proliferation of bone-marrow stromal cells in three-dimensional poly (ϵ-caprolactone)/hydroxyapatite/collagen scaffolds
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BACKGROUND: Osteoinduction and proliferation of bone-marrow stromal cells (BMSCs) in three-dimensional (3D) poly(ε-caprolactone) (PCL) scaffolds have not been studied throughly and are technically challenging. This study aimed to optimize nanocomposites of 3D PCL scaffolds to provide superior adhesion, proliferation and differentiation environment for BMSCs in this scenario. METHODS: BMSCs were isolated and cultured in a novel 3D tissue culture poly(ε-caprolactone) (PCL) scaffold coated with poly-lysine, hydroxyapatite (HAp), collagen and HAp/collagen. Cell morphology was observed and BMSC biomarkers for osteogenesis, osteoblast differentiation and activation were analyzed. RESULTS: Scanning Electron Microscope (SEM) micrographs showed that coating materials were uniformly deposited on the surface of PCL scaffolds and BMSCs grew and aggregated to form clusters during 3D culture. Both mRNA and protein levels of the key players of osteogenesis and osteoblast differentiation and activation, including runt-related transcription factor 2 (Runx2), alkaline phosphates (ALP), osterix, osteocalcin, and RANKL, were significantly higher in BMSCs seeded in PCL scaffolds coated with HAp or HAp/collagen than those seeded in uncoated PCL scaffolds, whereas the expression levels were not significantly different in collagen or poly-lysine coated PCL scaffolds. In addition, poly-lysine, collagen, HAp/collagen, and HAp coated PCL scaffolds had significantly more viable cells than uncoated PCL scaffolds, especially scaffolds with HAp/collagen and collagen-alone coatings. That BMSCs in HAp or HAp/collagen PCL scaffolds had remarkably higher ALP activities than those in collagen-coated alone or uncoated PCL scaffolds indicating higher osteogenic differentiation levels of BMSCs in HAp or HAp/collagen PCL scaffolds. Moreover, morphological changes of BMSCs after four-week of 3D culture confirmed that BMSCs successfully differentiated into osteoblast with spread-out phenotype in HAp/collagen coated PCL scaffolds. CONCLUSION: This study showed a proof of concept for preparing biomimetic 3D poly (ε-caprolactone)/ hydroxyapatite/collagen scaffolds with excellent osteoinduction and proliferation capacity for bone regeneration.
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Coating nano-HA and collagen over other scaffolds displays enhanced behavior as that of nano-HA/collagen.
“Therefore, coating nano-HA and collagen over other scaffolds also display enhanced behavior as that of nano-HA/collagen.”
From Nano-hydroxyapatite/collagen composite as scaffold material for bone regeneration. (2023) · cites this paper as [94]
The Results (ALP activity and cell proliferation) report increased BMSC proliferation on HAp–collagen-coated PCL scaffolds, and the Conclusions describe a favorable environment for osteogenesis. The study tested PCL scaffolds, however, so it does not establish the same enhanced behavior for scaffolds generally. (LLM, conf=0.83)
Experimental — accuracy not yet measuredExpression of factors responsible for osteogenesis and osteoconductivity was high on collagen and nano-HA coated PCL scaffold.
“Expression of factors responsible for osteogenesis and osteoconductivity were found to be high on collagen and nano-HA coated PCL scaffold.”
From Nano-hydroxyapatite/collagen composite as scaffold material for bone regeneration. (2023) · cites this paper as [94]
The Results section (page unavailable) reports higher expression of osteogenesis-related markers in BMSCs on hydroxyapatite/collagen-coated PCL scaffolds than on uncoated PCL scaffolds. It does not identify those markers as factors responsible for osteoconductivity or report their expression as a measure of osteoconductivity. (LLM, conf=0.84)
Experimental — accuracy not yet measuredBMSCs have multiple differentiation potential for therapeutic application when implanted with biodegradable scaffolds.
“Their multiple differentiation potential for therapeutic application when implanted with biodegradable scaffolds has been demonstrated in several previous studies [16–19].”
From Bone Mesenchymal Stem Cells Contribute to Ligament Regeneration and Graft–Bone Healing after Anterior Cruciate Ligament Reconstruction with Silk–Collagen Scaffold (2021) · cites this paper as [19]
The Introduction (page unavailable) says BMSCs can differentiate into multiple cell types and describes their potential use in bone-defect treatment. The Methods and Results (page unavailable) show BMSCs cultured on biodegradable PCL scaffolds and assess osteogenic differentiation, but do not demonstrate multiple differentiation outcomes after implantation or a therapeutic effect in vivo. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPoly lysine included in scaffold fabrication was not capable of enhancing osteogenic factors as much as a nano-HA/collagen coated scaffold.
“Even though poly lysine was included in the scaffold fabrication, they were not capable of enhancing osteogenic factors as that of nano-HA/ collagen coated scaffold.”
From Nano-hydroxyapatite/collagen composite as scaffold material for bone regeneration. (2023) · cites this paper as [94]
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- Authors
- Wang, T., Yang, X., Qi, X., & Jiang, C.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Northwestern University (US)
- Corresponding author
- Jiang, Chaoyin
- Venue
- Journal of Translational Medicine
- Published
- 2015-05-08
- Volume
- 13
- Issue
- 1
- Pages
- 152-152
- ISSN
- 1479-5876 (ISSN-L)
- PMC
- PMC4429830
- OpenAlex
- W1518134692
- Cited by
- 83
- References
- 52
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 9 · 2023: 7 · 2022: 10 · 2021: 8 · 2020: 4 · 2019: 10 · 2018: 9 · 2017: 7 · 2016: 9 · 2015: 2
- FWCI
- 4.47
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Translational Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Shanghai Jiao Tong University
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- mesenchymal stem cells, osteoinduction, osteogenic differentiation, poly(ε-caprolactone) scaffolds, hydroxyapatite coating, collagen coating, polylysine coating, 3D cell culture, cell proliferation, alkaline phosphatase activity, Runx2, RANKL, Osterix, osteocalcin, bone tissue engineering
- MeSH terms
- Animals, Bone and Bones, Bone Marrow, Cell Adhesion, Cell Differentiation, Cell Survival, Collagen, Microscopy, Electron, Scanning, Osteogenesis, Polyesters, Polylysine, Surface Properties, Biomarkers, Stromal Cells, Durapatite, Tissue Engineering, Biomimetics, Cell Proliferation, Rats, Tissue Scaffolds, Mesenchymal Stem Cells
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