Elevation of transforming growth factor beta (TGFβ) and its downstream mediators in subcutaneous foreign body capsule tissue

Abstract

Foreign body encapsulation represents a chronic fibrotic response and has been a major obstacle that reduces the useful life of implanted biomedical devices. The precise mechanism underlying such an encapsulation is still unknown. We hypothesized that, considering its central role in many other fibrotic conditions, transforming growth factor beta (TGFbeta) may play an important role during the formation of foreign body capsule (FBC). In the present study, we implanted mock sensors in rats subcutaneously and excised FBC samples at day 7, 21, and 48-55 postimplantation. The most abundant TGFbeta isoform in all tissues was TGFbeta1, which was expressed minimally in control tissue. The expression of both TGFbeta1 RNA and protein was significantly increased in FBC tissues at all time points, with the highest level in day 7 FBC. The number of cells stained for phosphorylated Smad2, an indication of activated TGFbeta signaling, paralleled the expression of TGFbeta. A similar dynamic change was also observed in the numbers of FBC myofibroblasts, which in response to TGFbeta, differentiate from quiescent fibroblasts and synthesize collagen. Type I collagen, the most prominent downstream target of TGFbeta in fibrosis, was found in abundance in the FBC, especially during the latter time periods. We suggest that TGFbeta plays an important role in the FBC formation. Inhibition of TGFbeta signaling could be a promising strategy in the prevention of FBC formation, thereby extending the useful life of subcutaneous implants.

Polycaprolactone nanofibrous mesh reduces foreign body reaction and induces adipose flap expansion in tissue engineering chamber

“…39 Foreign body encapsulation represents a chronic fibrotic response, and TGF-β has been considered an important cytokine in this process. [40][41][42] TGF-β is rapidly released from platelets to initiate the healing process upon injury, and is subsequently produced by inflammatory cells (especially macrophages) in the wounds. 40 In response to increased TGF-β, fibroblasts rapidly become activated and differentiate to myofibroblasts, which are characterized by a strong contractile capacity and high capacity for collagen synthesis.…”

“…[40][41][42] TGF-β is rapidly released from platelets to initiate the healing process upon injury, and is subsequently produced by inflammatory cells (especially macrophages) in the wounds. 40 In response to increased TGF-β, fibroblasts rapidly become activated and differentiate to myofibroblasts, which are characterized by a strong contractile capacity and high capacity for collagen synthesis. Under a normal wound-healing process, such a fibrotic response will ultimately minimize scarring and rebuild tissue integrity.…”

First step toward near-infrared continuous glucose monitoring: in vivo evaluation of antibody coupled biomaterials

“…Reducing capsule formation by bio-activating the materials surface has since long been the focus of many research teams. 3,[25][26][27][28] This can be realized by applying a number of approaches including among others plasma treatment and thin film modifications.…”

Tunable Microfibers Suppress Fibrotic Encapsulation via Inhibition of TGFβ Signaling

“…Recruited fibroblasts subsequently differentiate into myofibroblasts in response to the growth factor TGFb, and to mechanical tension present in the wound space. 4,5 TGFb activates expression of alpha smooth muscle actin (aSMA) and collagen, the major protein component of the fibrotic capsule. 5 The intracellular mechanisms involved in promotion of the myofibroblast phenotype via mechanosensing are still largely unknown, but they correlate with increased actin stress fiber formation, generation of internal cellular tension, and elongated cell shape.…”

“…4,5 TGFb activates expression of alpha smooth muscle actin (aSMA) and collagen, the major protein component of the fibrotic capsule. 5 The intracellular mechanisms involved in promotion of the myofibroblast phenotype via mechanosensing are still largely unknown, but they correlate with increased actin stress fiber formation, generation of internal cellular tension, and elongated cell shape. 4 Mechanical cues have been found to regulate the TGFb pathway in a variety of contexts, and therefore it is likely that these two types of cues closely interact to regulate myofibroblast differentiation and fibrotic encapsulation.…”