A pathophysiological examination of the biophysics and bioreactivity of silicone breast implants

doi:10.1016/0049-0172(94)90105-8

Seminars in Arthritis and Rheumatism

Volume 24, Issue 1, Supplement 1, August 1994, Pages 18-21

https://doi.org/10.1016/0049-0172(94)90105-8 Get rights and content

Abstract

Historically, silicones have been considered biologically inert materials, and have therefore been used widely in a variety of medical applications. Recently, controversy has arisen concerning the bioreactivity of silicone; reports of adverse inflammatory and immunological complications that may be evoked by silicone breast implants have appeared in the medical literature and have received great attention from the lay press. The phenomena said to be associated with silicones may be attributed pathophysiotogically to the inherent surface activity of silicone. The human body's initial response to the silicone of breast implants is the adsorption of various plasma proteins, including clotting and complement proteins, to the implant surface. Other macromolecules in the biological milieu may follow. The conformational integrity of this adsorbed macromolecular layer affects much of the subsequent biological reaction. Clinically silent inflammation, locally significant inflammation, inflammation with constitutional symptoms, and inflammation with immunological activation are possible consequences.

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Simultaneous analysis of multiple serum proteins adhering to the surface of medical grade polydimethylsiloxane elastomers
2007, Journal of Immunological Methods
Although polydimethylsiloxane (PDMS, silicone) elastomers are presumed to be chemically inert and of negligible toxicity, they induce a prompt acute inflammatory response with subsequent fibrotic reactions. Since local inflammatory and fibrotic side effects are associated with the proteinaceous film on the surface of silicone implants, the process of protein adherence to silicone is of practical medical relevance, and interesting from theoretical, clinical and biotechnological perspectives. It is hypothesized that the systemic side effects resembling rheumatoid and other connective tissue diseases may be triggered by local immunological changes, but this functional relationship has yet to be defined. Because the proteinaceous film on the surface of silicone has been identified as a key player in the activation of host defense mechanisms, we propose a test system based on a proteomics screen to simultaneously identify proteins adsorbed from serum to the surface of silicone. Herein, we describe protein adsorption kinetics on the surface of silicone implants, correlate the adhesion properties of serum proteins with the occurrence of adverse reactions to silicone, and successfully discriminate their signature on the silicone surface in a blinded study of patients suffering from fibrotic reactions (as determined by Baker scale) to silicone implants.
Silicone mammary implants - Can we turn back the time?
2007, Experimental Gerontology
Mankind remains infatuated with finding the “fountain of youth’’, and plastic surgery has become a very important component in the search for eternal youth. Invasive procedures such as face-lifts, body contouring, and implantation of silicone mammary implants (SMI) as well as less invasive procedures such as wrinkle decreasing protocols using filler substances or botulinum toxin, effectively reshape and rejuvenate the aging face or body. However, despite the improved cosmetic appearance of the individual, these treatments disrupt normal aging processes on cellular and molecular level. For example, silicone degradation products promote protein denaturation and activate cells of both the innate and adaptive immune system, thus perpetuating a chronic pro-inflammatory response of the local tissue. In this review, we concentrate on SMI and summarize the current clinical approaches, and the immunological and biochemical effects of those interventions.
Restricted and shared patterns of TCR β-chain gene expression in silicone breast implant capsules and remote sites of tissue inflammation
2000, Journal of Autoimmunity
Silicone breast implants (SBI) induce formation of a periprosthetic, often inflammatory, fibrovascular neo-tissue called a capsule. Histopathology of explanted capsules varies from densely fibrotic, acellular specimens to those showing intense inflammation with activated macrophages, multinucleated giant cells, and lymphocytic infiltrates. It has been proposed that capsule-infiltrating lymphocytes comprise a secondary, bystander component of an otherwise benign foreign body response in women with SBIs. In symptomatic women with SBIs, however, the relationship of capsular inflammation to inflammation in other remote tissues remains unclear. In the present study, we utilized a combination of TCR β-chain CDR3 spectratyping and DNA sequence analysis to assess the clonal heterogeneity of T cells infiltrating SBI capsules and remote, inflammatory tissues. TCR CDR3 fragment analysis of 22 distinct beta variable (BV) gene families revealed heterogeneous patterns of T cell infiltration in patients' capsules. In some cases, however, TCR BV transcripts exhibiting restricted clonality with shared CDR3 lengths were detected in left and right SBI capsules and other inflammatory tissues. DNA sequence analysis of shared, size-restricted CDR3 fragments confirmed that certain TCR BV transcripts isolated from left and right SBI capsules and multiple, extracapsular tissues had identical amino acid sequences within the CDR3 antigen binding domain. These data suggest that shared, antigen-driven T cell responses may contribute to chronic inflammation in SBI capsules as well as systemic sites of tissue injury.
Soft tissue response in the rabbit larynx following implantation of lactosorb (PLA/PGA copolymer) prosthesis for medialization laryngoplasty
2000, Journal of Voice
This project is designed to provide initial data regarding the use of polylactic acid/polyglycolic acid (PLA/PGA) copolymer (“LactoSorb” [Walter Lorenz Corp]), an alloplastic, resorbable material, as a prosthesis in an animal model of vocal fold medialization. Fifteen New Zealand white rabbits were utilized for left medialization laryngoplasty with LactoSorb implants after undergoing left recurrent laryngeal nerve section. At 1, 3, 6, and 9 months, the rabbits were sacrificed and their larynges were evaluated both grossly and histologically for tissue response to, and resorption characteristics of the implant, tissue cellularity, maintenance of vocal fold medialization, and airway patency. Additionally, 4 rabbits were used as controls, implanted with silicone rubber medialization implants, and sacrificed at 9 months for comparison. One rabbit underwent no surgery and was likewise used as a control. Grossly, no airway obstruction was noted, and no extrusions of the implants occurred. The LactoSorb implant maintained medialization in each group of sacrificed rabbits. Histologic findings revealed a very discrete, fibrous capsule around the implant in the 1- and 3-month rabbits, and the LactoSorb was still grossly visible. At 6 months, the thin fibrous capsule partially remained; at 9 months, the capsule was no longer evident, and the implant was no longer grossly visible. Endoscopic findings at the time of sacrifice in those rabbits implanted with silicone rubber included grossly patent airways with maintenance of medialization. In the rabbits implanted with silicone rubber, the histologic findings are similar to those described elsewhere.¹ LactoSorb, because of its intermittent resorption rate, could offer an ideal alternative to currently utilized temporary, or resorbable, materials, and as such will hopefully prove an invaluable tool in the laryngologist's treatment planning and surgical repair of the patient with a paralyzed vocal fold.
Dynamics of wound healing after silicone device implantation
1999, Experimental and Molecular Pathology
A large surgical wound is required for implantation of silicone mammary devices. Formation of capsules around silicone devices follows wound healing processes except that the healing is conformed and significantly delayed by the physical presence of the implant. Multilayered capsules are thicker and lymphocytic and plasmalymphocytic vasculitis, markers for delayed hypersensitivity, also correlate with thicker capsules. Polyurethane-coated devices induce very thick capsules that remain so for over 20 years. By contrast, gel and saline content devices show maximum thickness at 6.5 years. Active T_H lymphocyte memory does not differ by implant type for individuals with devices in place and that for gel content devices peaks at 10.5 years. There was a significant decrease in T cell indexes only after the removal of saline content devices. Comparison of the rate of formation of the periprosthetic capsule with the healing time of large wounds of similar size indicates that silicone devices interfere with the healing process, requiring substantially more time. This extended period has the potential for enhancing autoimmune conversion as a consequence of persistent delayed hypersensitivity.
In vitro activation of human monocytes by silicones
1998, Colloids and Surfaces B: Biointerfaces
The effect of silicone biomaterials on the immune system still remains largely unknown. This study was undertaken to determine the extent to which silicone elastomer, with or without either pre-adsorbed human serum albumin (HSA), IgG, fibrinogen or whole plasma, can activate peripheral blood monocytes. Monocytes were isolated from buffy coats from the local Red Cross Blood Center. Monocytes were cultured for 18 h, culture supernatant collected, and analyzed for IL-1β, IL-6 and TNF-α by employing commercial ELISA kits. Monocytes, in contact with either polystyrene or silicones without protein adsorption, were minimally activated as evidenced by the low concentration of all the cytokines measured. On the other hand, monocytes became activated when in contact with silicones having adsorbed either of the above proteins. The silicone gel, silicone oil and silicone gel/oil combination appeared to cause the monocytes to secrete nearly twice the amount of all three cytokines as compared with silicone elastomer. This result may be a function of the increased effective surface area produced by the silicone gels and silicone oils. Contact angle measurements confirm that silicones have a very hydrophobic surface, whereas tissue culture grade polystyrene (TPST) is hydrophilic. We know that hydrophobic surfaces tend to be much more denaturing to adsorbed proteins than hydrophilic surfaces. Thus our results indicate that plasma proteins adsorbed to very hydrophobic surfaces cause monocytes to secrete significant amounts of IL-1β, IL-6 and TNF-α.

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^☆: From a paper presented at the George Washington University sponsored Silicone-Related Disorders: A Symposium, December 1992, Washington, DC.

^☆☆: Supported by the Biomaterials Bioreactivity Characterization Fund, UCLA School of Medicine, Los Angeles, CA.

¹: From the Biomaterials Bioreactivity Characterization Laboratory, Department of Pathology and Laboratory Medicine, University of California, Los Angeles School of Medicine, Los Angeles, CA.

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A pathophysiological examination of the biophysics and bioreactivity of silicone breast implants☆,☆☆

Abstract

Lancet

Silicone Breast Implants and Immune Disease

Annals of Plastic Surgery

Report presented before the General and Plastic Surgery Device Evaluation Panel

Principles of Colloid and Surface Chemistry

Organic polymer biocompatibility and toxicology (review)

Clin Chem

NIH Contract PH-43-64-496, Development of Blood Compatible Polymeric Materials, Report

Electrophoresis of adsorbed proteins

J Am Chem Soc

Intermolecular and surface forces

The bioreactivity of silicone

CRC Critical Reviews in Biocompatibility

Physical Chemistry

Adsorption of proteins by polystyrene particles. I. Molecular unfolding and acquired immunogenicity of IgG

J Immunol

Bioreactivity and the growing controversy of silicone breast prosthesis