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Role of Connective Tissue Growth Factor in Breast Implant Elastomer Capsular Formation
Abstract
Transforming growth factor-beta (TGF-beta) has been demonstrated to be a mediator in scar formation and in multiple fibrotic disorders such as in Dupuytren contractures and in pulmonary fibrosis. Recently, it has been demonstrated that connective tissue growth factor (CTGF) is a downstream mediator of TGF-beta and acts to stimulate wound contraction and fibrosis. The purpose of this study is to assess the role of CTGF in the development of breast implant elastomer capsule formation over time and to evaluate the effects of TGF-beta and CTGF antisense (AS) oligonucleotides on capsule formation. Fifteen Sprague-Dawley rats were randomly assigned to treatment (n = 12) and control (n = 3) groups. Four 2- x 2-cm pockets were created on the dorsum deep to the panniculus carnosus in each rat. A 1- x 1-cm smooth breast implant elastomer was placed. Each rat in the treatment group received 1 ml vehicle, AS-TGF-beta, AS-CTGF, or scramble antisense oligonucleotide (AS-scramble). Control rats received either 1 ml vehicle or 1 ml saline in each pocket. At weeks 1, 3, and 5, four treatment rats and one control rat were randomly selected and killed. Tissue blocks were harvested for determination of CTGF levels using the enzyme-linked immunosorbent assay technique and for hematoxylin and eosin slides to evaluate capsule formation. Levels of CTGF in capsular tissue treated with vehicle or AS-scrambled were similar and progressively increased in tissues on weeks 1, 3, and 5, compared with normal skin. At weeks 1 and 3 after surgery, levels of CTGF were suppressed in capsules treated with AS-CTGF or AS-TGF-beta compared with normal skin and with tissues treated with vehicle or AS-scramble (p = 0.002). At week 5, levels of CTGF were similar to levels in normal skin. Histological analysis revealed reduced capsular formation in samples treated with AS-CTGF or AS-TGF-beta compared with the two other treated sites. In conclusion, a single and local treatment with AS-CTGF or AS-TGF-beta at the time of surgery reduced CTGF levels in tissue and correlated with reduced capsular formation in a rat model. These data suggest a new therapeutic strategy to reduce early capsular formation based on local application of antisense oligonucleotides targeting CTFG and TGF-beta.
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Local inhibition of TGF-β through injection of anti-sense oligonucleotides has been shown to decrease capsule formation in subcutaneous implants.
“Local inhibition of TGF-β through injection of anti-sense oligonucleotides has been shown to decrease capsule formation in subcutaneous implants (Mazaheri et al., 2003).”
From Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics (2021) · cites this paper as Mazaheri et al., 2003
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References 28 · Cited by 43
Research works printed but not linked: 3
- Abbondanzo, 1999, Mod Pathol, 12, 706
- Parsons, 1983, Trans Int Congress Plast Reconstr Surg, &NA;, 18
- Lee, 1999, Ann Plast Surg, 43, 179
Metadata
- Authors
- Mazaheri, M. K., Schultz, G. S., Blalock, T. D., Caffee, H. H., & Chin, G. A.
- Affiliations
- University of Florida Health (US)
- Corresponding author
- Mazaheri, Mehdi K.
- Caffee, H. Hollis
- Chin, Gloria A.
- Venue
- Annals of Plastic Surgery
- Published
- 2003-03
- Volume
- 50
- Issue
- 3
- Pages
- 263-268
- ISSN
- 0148-7043 (ISSN-L)
- OpenAlex
- W1971556223
- Cited by
- 43
- References
- 28
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 1 · 2016: 1 · 2015: 1 · 2014: 4 · 2013: 2 · 2012: 2
- FWCI
- 2.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Plastic Surgery (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Breast Implant and Reconstruction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
- Health Sciences › Medicine › Dermatology › Facial Rejuvenation and Surgery Techniques
- Keywords
- connective tissue growth factor, TGF-beta, capsular contracture, antisense oligonucleotides, fibrosis, scar formation, local gene therapy, rat model, breast augmentation complications, wound contraction
- MeSH terms
- Animals, Fibrosis, Mitogens, Postoperative Complications, Wound Healing, Transforming Growth Factor beta, Oligonucleotides, Antisense, Rats, Sprague-Dawley, Immediate-Early Proteins, Breast Implants, Insulin-Like Growth Factor Binding Proteins, Elastomers, Models, Animal, Intercellular Signaling Peptides and Proteins, Rats, Connective Tissue Growth Factor
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