Biomaterial topography alters healing in vivo and monocyte/macrophage activation in vitro
Open accessAbstract
The effect of biomaterial topography on healing in vivo and monocyte/macrophage stimulation in vitro was assessed. A series of expanded polytetrafluoroethylene (ePTFE) materials were characterized by increasing average intranodal distance of 1.2 μm (1.2‐ePTFE), 3.0 μm (3.0‐ePTFE), and 4.4 μm (4.4‐ePTFE), but presented consistent surface chemistry with nonporous PTFE (np‐PTFE). Subcutaneous implantation of 4.4‐ePTFE into mice resulted in a statistically thinner capsule that appeared less organized and less dense than the np‐PTFE response. In vitro, isolated monocytes/macrophages cultured on np‐PTFE produced low levels of interleukin 1‐beta (IL‐1β), 1.2‐ePTFE and 3.0‐ePTFE stimulated intermediate levels, and 4.4‐ePTFE stimulated a 15‐fold increase over np‐PTFE. Analysis of cDNA microarrays demonstrated that additional proinflammatory cytokines and chemokines, including IL‐1β, interleukin 6, tumor necrosis factor alpha, monocyte chemotactic protein 1, and macrophage inflammatory protein 1‐beta, were expressed at higher levels by monocytes/macrophages cultured on 4.4‐ePTFE at 4 and 24 h, respectively. Expression ratios for several genes were quantified by RT‐PCR and were consistent with those from the cDNA array results. These results demonstrate the effect of biomaterial topography on early proinflammatory cytokine production and gene transcription by monocytes/macrophages in vitro and decreased fibrous capsule thickness in vivo. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
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Pore size solely increased IL-1β expression, as low levels were produced by macrophages in nonporous structures, while a gradual increase in IL-1β production was observed by macrophages in porous structures of 0.2, 1, and 3 μm.
“Pore size solely increased IL‐1β expression, as low levels were produced by macrophages in nonporous structures, while a gradual increase in IL‐1β production was observed by macrophages in porous structures of 0.2, 1, and 3 µm.”
From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [135]
The Results section on cytokine secretion reports low IL-1β production on nonporous PTFE and increasing production across the porous materials. But the reported dimensions are 1.2, 3.0, and 4.4 µm, not 0.2, 1, and 3 µm. The Results section on cytokine gene expression also reports increases in other proinflammatory cytokines, so an IL-1β-only reading of “solely” is not supported. Page numbers are unavailable in our copy. (LLM, conf=0.90)
Experimental — accuracy not yet measuredIn vivo studies displayed a thinner, less dense, organized FBC formation in 3 μm porous structures compared to nonporous structures, suggesting that polarization of M1 macrophages in vitro may not be an indication of thicker FBC formation in vivo.
“Moreover, in vivo studies displayed a thinner, less dense, organized FBC formation in 3 µm porous structures compared to nonporous structures, suggesting that polarization of M1 macrophages in vitro may not be an indication of thicker FBC formation in vivo.”
From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [135]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredThe 3 μm porous structures provided an increase in levels of IL-6, TNF-α, MCP-1, and MIP-1β when compared to the nonporous substrate.
“These results revealed that the 3 µm porous structures provided an increase in levels of IL‐6, TNF‐α, MCP‐1, and MIP‐1β when compared to the nonporous substrate.”
From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [135]
The Results sections on cytokine and chemokine gene expression report higher IL-6, TNF, MCP-1, and MIP-1β expression on 4.4-µm ePTFE than on nonporous PTFE—not on 3.0-µm ePTFE. The monocyte/macrophage secretion results report an intermediate increase for 3.0-µm ePTFE only for IL-1β. The claim therefore assigns the four-marker finding to the wrong pore size. (LLM, conf=0.90)
Experimental — accuracy not yet measuredThe fibrous capsule thickness for the softest hydrogels is on par with those reported for expanded polytetrafluoroethylene, degradable polyester polyurethanes, polycaprolactone, and polyethylene terephthalate.
“This thickness is on par with those reported with other materials, such as expanded polytetrafluoroethylene,51 degradable polyester polyurethanes,52 polycaprolactone,53 and polyethylene terephthalate.54”
From Student award winner in the undergraduate category for the society of biomaterials 9th World Biomaterials Congress, Chengdu, China, June 1–5, 2012: The effects of substrate stiffness on the <i>in vitro</i> activation of macrophages and <i>in vivo</i> host response to poly(ethylene glycol)‐based hydrogels (2012) · cites this paper as [51]
Micro-scale surface features seem to increase macrophage adhesion and release of inflammatory mediators such as IL-1β, IL-6, and nitric oxide relative to smooth surfaces.
“surfaces that contain micro-scale features appeared to enhance the adhesion of macrophages and their secretion of inflammatory cytokines including IL-1β, IL-6, and nitric oxide when compared to macrophages on smooth surfaces.8-11”
From Micro- and Nanopatterned Topographical Cues for Regulating Macrophage Cell Shape and Phenotype (2015) · cites this paper as [11]
Biomaterial surface topography can modulate macrophage polarization.
“Similarly, recent studies have also shown potential modulating effects of biomaterial surface topography upon macrophage polarization [150,151].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [151]
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- Authors
- Bota, P. C. S., Collie, A. M. B., Puolakkainen, P., Vernon, R. B., Sage, E. H., Ratner, B. D., & Stayton, P. S.
- Affiliations
- University of Washington (US)
- Cleveland Clinic (US)
- Helsinki University Hospital (FI)
- Benaroya Research Institute (US)
- Corresponding author
- Collie, Angela M. B.
- Venue
- Journal of Biomedical Materials Research Part A
- Publisher
- Wiley
- Published
- 2010-08-19
- Volume
- 95A
- Issue
- 2
- Pages
- 649-657
- ISSN
- 1549-3296 (ISSN-L)
- 1552-4965
- PMC
- PMC4235956
- OpenAlex
- W2020382590
- Cited by
- 186
- References
- 31
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 10 · 2023: 8 · 2022: 10 · 2021: 14 · 2020: 14 · 2019: 15 · 2018: 6 · 2017: 16 · 2016: 16 · 2015: 19 · 2014: 15 · 2013: 13 · 2012: 8
- FWCI
- 10.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Biomedical Materials Research Part A (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Washington
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM045873, T32GM007266, GM045873, T32GM065098)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Keywords
- expanded polytetrafluoroethylene, polytetrafluoroethylene, monocyte/macrophage activation, inflammatory cytokines, IL-1β, fibrous capsule formation, subcutaneous implantation, gene expression, chemokines, TNF-α, interleukin-6, macrophage inflammatory protein-1β, MCP-1, tissue repair
- MeSH terms
- Animals, Biocompatible Materials, Cells, Cultured, Humans, Macrophage Activation, Macrophages, Male, Materials Testing, Monocytes, Polytetrafluoroethylene, Surface Properties, Cytokines, Chemokines, Oligonucleotide Array Sequence Analysis, Intercellular Signaling Peptides and Proteins, Mice
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