Temporal progression of the host response to implanted poly(ethylene glycol)‐based hydrogels
Open accessAbstract
Poly(ethylene glycol) (PEG) hydrogels hold great promise as in vivo cell carriers for tissue engineering. To ensure appropriate performance of these materials when implanted, the host response must be well understood. The objectives for this study were to characterize the temporal evolution of the foreign body reaction (FBR) to acellular PEG‐based hydrogels prepared from PEG diacrylate precursors when implanted subcutaneously in immunocompentent c57bl/6 mice by (immuno)histochemical analysis and gene expression. Compared with a normal FBR elicited by silicone (SIL), PEG hydrogels without or with a cell adhesion ligand RGD elicited a strong early inflammatory response evidenced by a thick band of macrophages as early as day 2, persisting through two weeks, and by increased interleukin‐1β expression. PEG‐only hydrogels showed a slower, but more sustained progression of inflammation over PEG‐RGD. Temporal changes in gene expression were observed in response to PEG‐based materials and in general exhibited, elevated expression of inflammatory and wound healing genes in the tissues surrounding the implants, while the expression patterns were more stable in response to SIL. While a stabilized FBR was achieved with SIL and to a lesser degree with PEG‐RGD, the PEG‐only hydrogels had not yet stabilized after 4 weeks. In summary, PEG‐only hydrogels elicit a strong early inflammatory reaction, which persists throughout the course of the implantation even as a collagenous capsule begins to form. However, the incorporation of RGD tethers partially attenuates this response within 2 weeks leading to an improved FBR to PEG‐based hydrogels. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 2011.
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A strong early inflammatory reaction with a large band of macrophages at the hydrogel surface and elevated IL-1β expression occurs within two days post-implantation and persists throughout four weeks with little stabilization.
“A strong early inflammatory reaction, characterized by a large band of macrophages at the hydrogel surface, ensues within two days post-implantation along with elevated levels of interleukin-1β expression in the cells at and near the implant interface. This reaction persists throughout the four weeks, with little sign of stabilization.”
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 [15]
PEG-based hydrogels formed from PEG diacrylate precursors elicit a foreign body reaction when implanted subcutaneously in immunocompetent mice.
“We recently demonstrated that PEG-based hydrogels formed from PEG diacrylate precursors indeed elicit a FBR when implanted subcutaneously in immunocompetent mice.15,16”
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 [15]
The authors previously reported that PEG-only hydrogels with no biological recognition and properties resembling 240 kPa gels led to an atypical FBR characterized by many macrophages persisting at the implant surface with no obvious stabilization by 28 days.
“We previously reported that PEG-only hydrogels with no biological recognition and with properties resembling those of the 240 kPa gels, led to an atypical FBR characterized by a large number of macrophages persisting at the implant surface with no obvious signs of stabilization by 28 days.15”
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 [15]
Previous findings by the authors showed that RGD attenuates, but does not completely eliminate, the foreign body response to PEG hydrogels.
“Our previous findings showed that RGD is able to attenuate, although not completely, the FBR to PEG hydrogels.15,16”
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 [15]
The response was improved with 240 kPa hydrogels and results were similar to previous reports, but the FBR was still largely atypical.
“The response was improved with 240 kPa and results were similar to that of our previous reports, but the FBR was still largely atypical.15”
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 [15]
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References 42 · Cited by 77
Research works printed but not linked: 1
- [40]Nho YC Moon SW Lee KH Park CW Suh TS Jung YA Ahn WS Chun HJ Evaluations of poly(vinyl alcohol) hydrogels cross-linked under gamma-ray irradiation Journal of Industrial and Engineering Chemistry 2005 11 1 159 164
- Authors
- Lynn, A. D., Blakney, A. K., Kyriakides, T. R., & Bryant, S. J.
- Affiliations
- University of Colorado Boulder (US)
- Yale University (US)
- Corresponding author
- Bryant, Stephanie J.
- Venue
- Journal of Biomedical Materials Research Part A
- Publisher
- Wiley
- Published
- 2011-01-25
- Volume
- 96A
- Issue
- 4
- Pages
- 621-631
- ISSN
- 1549-3296 (ISSN-L)
- 1552-4965
- PMC
- PMC3091279
- OpenAlex
- W1969165091
- Cited by
- 77
- References
- 42
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 2 · 2023: 4 · 2022: 5 · 2021: 7 · 2020: 7 · 2019: 7 · 2018: 7 · 2017: 5 · 2016: 7 · 2015: 5 · 2014: 8 · 2013: 1 · 2012: 3
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Biomedical Materials Research Part A (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r01gm072194-11)
- National Institute of General Medical Sciences (R01-GM072194)
- National Institute of Dental and Craniofacial Research (1R03DE0195051, R03DE019505)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Keywords
- poly(ethylene glycol) hydrogels, foreign body reaction, host response to implants, RGD peptide, inflammation, macrophages, IL-1β, gene expression, collagen capsule, tissue engineering scaffolds, wound healing genes
- MeSH terms
- Animals, Biocompatible Materials, Foreign-Body Reaction, Macrophages, Male, Mice, Inbred C57BL, Polyethylene Glycols, Implants, Experimental, Hydrogels, Tissue Engineering, Mice
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