Silicone Breast Implant Surface Texture Impacts Gene Expression in Periprosthetic Fibrous Capsules

Abstract

Background: Silicone breast implants with smooth outer shells are associated with higher rates of capsular contracture, whereas textured implants have been linked to the development of breast implant-associated anaplastic large cell lymphoma. By assessing the gene expression profile of fibrous capsules formed in response to smooth and textured implants, insight into the development of breast implant-associated abnormalities can be gained. Methods: Miniature smooth or textured silicone implants were surgically inserted into female rats (n = 10) and harvested for the surrounding capsules at postoperative week 6. RNA sequencing and quantitative polymerase chain reaction were performed to identify genes differentially expressed between smooth and textured capsules. For clinical correlation, the expression of candidate genes was assayed in implant capsules harvested from human patients with and without capsular contracture. Results: Of 18,555 differentially expressed transcripts identified, three candidate genes were selected: matrix metalloproteinase-3 (MMP3), troponin-T3 (TNNT3), and neuregulin-1 (NRG1). In textured capsules, relative gene expression and immunostaining of MMP3 and TNNT3 was up-regulated, whereas NRG1 was down-regulated compared to smooth capsules [mean relative fold change, 8.79 (P = 0.0059), 4.81 (P = 0.0056), and 0.40 (P < 0.0001), respectively]. Immunostaining of human specimens with capsular contracture revealed similar gene expression patterns to those of animal-derived smooth capsules. Conclusions: An expression pattern of low MMP3/low TNNT3/high NRG1is specifically associated with smooth implant capsules and human implant capsules with capsular contracture. The authors’ clinically relevant breast implant rat model provides a strong foundation to further explore the molecular genetics of implant texture and its effect on breast implant-associated abnormalities. Clinical Relevance Statement: The authors have demonstrated that there are distinct gene expression profiles in response to smooth versus textured breast implants. Since surface texture may be linked to implant-related pathology, further molecular analysis of periprosthetic capsules may yield strategies to mitigate implant-related complications.

Implant Texture and Capsular Contracture: A Review of Cellular and Molecular Pathways

“…Capsules of smooth and textured implants differ in their composition; smooth implant capsules are associated with lower collagen amount, 23 reduced thickness, 23 , 24 increased parallel arrangement of collagen, 23 , 25 and reduced sheer frictional force. 26 Textured implants are associated with more ridged and less continuous capsules 8 with more compact collagen arrangement, 24 and thicker capsular epithelium 8 when compared with smooth implant capsules. Synovial metaplasia 24 and increased cell death 26 are more commonly observed in capsules surrounding macrotexturized implants than smooth implants.…”

“…Normal capsules have increased MMP3 expression when compared with contracted capsules. 8 Also, textured implants have higher MMP3 expression when compared with smooth. 8 MMP2, MMP9, or MMP12 are similar in smooth and microtextured implants; however, MMP9 and MMP12 are heavily upregulated in macrotextured implants.…”

“… 8 Also, textured implants have higher MMP3 expression when compared with smooth. 8 MMP2, MMP9, or MMP12 are similar in smooth and microtextured implants; however, MMP9 and MMP12 are heavily upregulated in macrotextured implants. 55 Tissue inhibitor of metalloproteinase (TIMP) is a known inhibitor of MMPs.…”

“…Various causative mechanisms have been proposed to explain the transition from a normal capsule to a fibrous contracted capsule. [2][3][4][6][7][8] Chronic inflammation of the periprosthetic tissue is hypothesized to be a hallmark of this transition, stimulated by subclinical bacterial infection with biofilm formation, hematoma, or seroma. 5 The cellular and molecular mechanisms of this prolonged inflammatory response are not well characterized.…”