The healing of bony defects by cell-free collagen-based scaffolds compared to stem cell-seeded tissue engineered constructs
Abstract
One of the key challenges in tissue engineering is to understand the host response to scaffolds and engineered constructs. We present a study in which two collagen-based scaffolds developed for bone repair: a collagen-glycosaminoglycan (CG) and biomimetic collagen-calcium phosphate (CCP) scaffold, are evaluated in rat cranial defects, both cell-free and when cultured with MSCs prior to implantation. The results demonstrate that both cell-free scaffolds showed excellent healing relative to the empty defect controls and somewhat surprisingly, to the tissue engineered (MSC-seeded) constructs. Immunological analysis of the healing response showed higher M1 macrophage activity in the cell-seeded scaffolds. However, when the M2 macrophage response was analysed, both groups (MSC-seeded and non-seeded scaffolds) showed significant activity of these cells which are associated with an immunomodulatory and tissue remodelling response. Interestingly, the location of this response was confined to the construct periphery, where a capsule had formed, in the MSC-seeded groups as opposed to areas of new bone formation in the non-seeded groups. This suggests that matrix deposited by MSCs during in vitro culture may adversely affect healing by acting as a barrier to macrophage-led remodelling when implanted in vivo. This study thus improves our understanding of host response in bone tissue engineering.
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Marked differences in M1 and M2 presence are observed 4 and 8 weeks after implantation of cell-free and MSC-filled porous collagen-based scaffolds.
“Research from our group suggests that marked differences in M1 and M2 presence is observed 4 and 8 weeks after implantation of cell free and MSC filled porous collagen-based scaffolds (Fig. 6a,b,e,f) [82]”
From Biomaterial based modulation of macrophage polarization: a review and suggested design principles (2015) · cites this paper as [82]
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- Authors
- Lyons, F. G., Al-Munajjed, A. A., Kieran, S. M., Toner, M. E., Murphy, C. M., Duffy, G. P., & O’Brien, F. J.
- Affiliations
- Royal College of Surgeons in Ireland (IE)
- Trinity College Dublin (IE)
- Corresponding author
- O’Brien, Fergal J.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 31
- Issue
- 35
- Pages
- 9232-9243
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2060078219
- Cited by
- 222
- References
- 54
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 3 · 2023: 11 · 2022: 17 · 2021: 14 · 2020: 11 · 2019: 24 · 2018: 18 · 2017: 15 · 2016: 15 · 2015: 20 · 2014: 20 · 2013: 18 · 2012: 12
- FWCI
- 8.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion)
- Funders
- Enterprise Ireland
- Science Foundation Ireland (04/Yl1/B531, 06/RFP/ENM012)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Materials Science › Biomaterials › Collagen: Extraction and Characterization
- Keywords
- bone defect repair, collagen scaffolds, cell-free scaffolds, mesenchymal stem cells, cranial defects, macrophage polarization, M1 macrophages, M2 macrophages, collagen-glycosaminoglycan scaffolds, bone tissue engineering, capsule formation, bone remodeling
- MeSH terms
- Animals, Biomechanical Phenomena, Bone Regeneration, Calcium Phosphates, Collagen, Glycosaminoglycans, Macrophages, Male, Wound Healing, Rats, Wistar, Tissue Engineering, Rats, Tissue Scaffolds, X-Ray Microtomography, Mesenchymal Stem Cells
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