Use of the Transforming Growth Factor-??1 Inhibitor Peptide in Periprosthetic Capsular Fibrosis: Experimental Model with Tetraglycerol Dipalmitate

Ruiz-de-Erenchun, R.; Herrerias, J. Dotor De Las; Hontanilla, Bernardo

doi:10.1097/01.prs.0000181694.07661.0d

Cited by 44 publications

(20 citation statements)

References 31 publications

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“…High levels of TGF-β and IL-1 could potentially result in significant fibrosis surrounding silicone implants in vivo . The TGF-β1 inhibitor peptide was significantly effective in achieving a reduction in periprosthetic fibrosis after silicone implants placements [29]. This explains the fibrous capsule formation inhibiting effect of Tan IIA in our experiment.…”

Section: Discussionsupporting

confidence: 59%

Tanshinon IIA Injection Accelerates Tissue Expansion by Reducing the Formation of the Fibrous Capsule

Sheng²,

Yang³

et al. 2014

PLoS ONE

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The tissue expansion technique has been applied to obtain new skin tissue to repair large defects in clinical practice. The implantation of tissue expander could initiate a host response to foreign body (FBR), which leads to fibrotic encapsulation around the expander and prolongs the period of tissue expansion. Tanshinon IIA (Tan IIA) has been shown to have anti-inflammation and immunoregulation effect. The rat tissue expansion model was used in this study to observe whether Tan IIA injection systematically could inhibit the FBR to reduce fibrous capsule formation and accelerate the process of tissue expansion. Forty-eight rats were randomly divided into the Tan IIA group and control group with 24 rats in each group. The expansion was conducted twice a week to maintain a capsule pressure of 60 mmHg. The expansion volume and expanded area were measured. The expanded tissue in the two groups was harvested, and histological staining was performed; proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) and transforming growth factor-β (TGF-β) were examined. The expansion volume and the expanded area in the Tan IIA group were greater than that of the control group. The thickness of the fibrous capsule in the Tan IIA group was reduced with no influence on the normal skin regeneration. Decreased infiltration of macrophages, lower level of TNF-α, IL-6, IL-1β and TGF-β, less proliferating myofibroblasts and enhanced neovascularization were observed in the Tan IIA group. Our findings indicated that the Tan IIA injection reduced the formation of the fibrous capsule and accelerated the process of tissue expansion by inhibiting the FBR.

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Section: Discussionsupporting

confidence: 59%

Tanshinon IIA Injection Accelerates Tissue Expansion by Reducing the Formation of the Fibrous Capsule

Sheng²,

Yang³

et al. 2014

PLoS ONE

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“…Rabbits 16,17,29,30 and rats 18,19,31 serve as well-established models, and pig models 32 have also been described. We chose an Old World primate known to exhibit considerable genetic homology with humans, 33 with the expectation that the immunologic and tissue maintenance mechanisms would most closely approximate those seen in humans.…”

Section: Discussionmentioning

confidence: 99%

“…15,16 The leukotriene inhibitor zafirlukast and a transforming growth factor-␤1 inhibitor peptide likewise have been shown effective in decreasing capsule thickness in rat studies. 17,18 In this experiment, we sought to evade cellular mechanisms of fibrosis by sequestering the implant beneath a layer of acellular dermal matrix (AlloDerm; LifeCell Corp., Branchburg, N.J.).…”

mentioning

confidence: 99%

The Use of Acellular Dermal Matrix to Prevent Capsule Formation around Implants in a Primate Model

Stump

Holton

Connor

et al. 2009

Plastic and Reconstructive Surgery

150

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“…Previous studies have demonstrated that TGF-β is a potent target for anti-fibrotic therapy. (55, 57–59) These studies show anti-fibrotic efficacy of TGF-β siRNA to prevent fibrosis in vivo using different delivery systems. However, TGF-β siRNA showed no detectable anti-fibrotic activity as collagen capsule thickness was unaffected by the TGF-β siRNA in the murine implant model.…”

Section: Discussionmentioning

confidence: 94%

Device-based local delivery of siRNA against mammalian target of rapamycin (mTOR) in a murine subcutaneous implant model to inhibit fibrous encapsulation

Takahashi

Wang

Grainger

2010

Journal of Controlled Release

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Fibrous encapsulation of surgically implant devices is associated with elevated proliferation and activation of fibroblasts in tissues surrounding these implants, frequently causing foreign body complications. Here we test the hypothesis that inhibition of the expression of mammalian target of rapamycin (mTOR) in fibroblasts can mitigate the soft tissue implant foreign body response by suppressing fibrotic responses around implants. In this study, mTOR was knocked down using small interfering RNA conjugated with branched cationic polyethylenimine (bPEI) in fibroblastic lineage cells in serum-based cell culture as shown by both gene and protein analysis. This mTOR knockdown led to an inhibition in fibroblast proliferation by 70% and simultaneous down-regulation in the expression of type I collagen in fibroblasts in vitro. These siRNA/bPEI complexes were released from poly(ethylene glycol) (PEG)-based hydrogel coatings surrounding model polymer implants in a subcutaneous rodent model in vivo. No significant reduction in fibrous capsule thickness and mTOR expression in the foreign body capsules was observed. Observed siRNA inefficacy in this in vivo implant model was attributed to siRNA dosing limitations in the gel delivery system, and lack of targeting ability of the siRNA complex specifically to fibroblasts. While in vitro data supported mTOR knock-down in fibroblast cultures, in vivo siRNA delivery must be further improved to produce clinically relevant effects on fibrotic encapsulation around implants.

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Use of the Transforming Growth Factor-??1 Inhibitor Peptide in Periprosthetic Capsular Fibrosis: Experimental Model with Tetraglycerol Dipalmitate

Abstract: The TGF-beta1 inhibitor peptide applied in a matrix with tetraglycerol dipalmitate is significantly effective in achieving a reduction in periprosthetic fibrosis after placement of silicone implants, either subcutaneously or submuscularly. This result suggests new therapeutic approaches.

Cited by 44 publications

References 31 publications

Tanshinon IIA Injection Accelerates Tissue Expansion by Reducing the Formation of the Fibrous Capsule

Tanshinon IIA Injection Accelerates Tissue Expansion by Reducing the Formation of the Fibrous Capsule

The Use of Acellular Dermal Matrix to Prevent Capsule Formation around Implants in a Primate Model

Device-based local delivery of siRNA against mammalian target of rapamycin (mTOR) in a murine subcutaneous implant model to inhibit fibrous encapsulation

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