The effect of amphiphilic siloxane oligomers on fibroblast and keratinocyte proliferation and apoptosis

Abstract

The formation of hypertrophic scars (HSF) is a frequent medical outcome of wound repair and often requires further therapy with treatments such as silicone gel sheets (SGS) or apoptosis-inducing agents, including bleomycin. Although widely used, knowledge regarding SGS and their mode of action is limited. Preliminary research has shown that small amounts of amphiphilic silicone present in SGS have the ability to move into skin during treatment. We demonstrate herein that a commercially available analogue of these amphiphilic siloxane species, the rake copolymer GP226, decreases collagen synthesis on exposure to cultures of fibroblasts derived from HSF. By size exclusion chromatography, GP226 was found to be a mixture of siloxane species, containing five fractions of different molecular weight. By studies of collagen production, cell viability and proliferation, it was revealed that a low molecular weight fraction (fraction IV) was the most active, reducing the number of viable cells present after treatment and thereby reducing collagen production as a result. On exposure of fraction IV to human keratinocytes, viability and proliferation were also significantly affected. HSF undergoing apoptosis after application of fraction IV were also detected via real-time microscopy and by using the TUNEL assay. Taken together, these data suggests that these amphiphilic siloxanes could be potential non-invasive substitutes to apoptotic-inducing chemical agents that are currently used as scar treatments.

An investigation into the effect of amphiphilic siloxane oligomers on dermal fibroblasts

“…The plot suggests that zero proliferation will occur at 100HLB/MW of 0.65-0.9 (from extrapolation to the x-axis), dependent on concentration. This hypothesis is supported by the previously studied rake system, 12 which has a calculated value of 0.9 for 100HLB/MW and showed a down-regulation of fibroblast proliferation to 0.05 at a concentration of 0.10 wt%, consistent with the extrapolation of the results from the PEG-PDMS-PEG block copolymers shown in Figure 6.…”

“…The motivation behind the present research was based on our previous findings12 which demonstrated that exposure to PDMS–PEG rake copolymers reduced cell viability and proliferation. Results suggested the effect on cell viability and proliferation was related to the MW of the copolymer.…”

“…9 Despite the fact that copolymers of PEG and PDMS are certified for topical application, 10,11 we have recently reported that certain rake-type PDMS-PEG copolymers affect both dermal fibroblasts and keratinocytes in vitro by reducing proliferation, viability, and fibroblast collagen synthesis. 12 The effect is strongly related to molecular weight (MW): from a study of the different copolymer fractions separated by preparative size exclusion chromatography, it was found that the lower MW fractions had the greatest impact on both cell types. This observation that nonionic amphiphilic copolymers can have adverse effects on cells is not unique to PDMS-PEG copolymers.…”

“…16 This was based on the data showing that low MW hydroxyl-terminated linear oligomers are able to diffuse through the stratum corneum 17 at a rate similar to small hydrophobic molecules of 2.5 Â 10 À9 cm 2 s À1 . 18 These studies, along with examination of the rake copolymers, 12 suggest that the PDMS-PEGs have potential as a scar therapy and may provide a substitute for SGS or an alternative to other therapies commonly used, such as injections of antiproliferative agents 5-FU 19 or bleomycin, 20 treatment with specific cytokines, extra cellular matrix modulators, or growth factors. 21 In this study, we have investigated whether well-defined ABA PDMS-PEG block co-oligomers can emulate the effects of the low MW rake copolymers previously studied.…”

Culture of Primary Bovine Chondrocytes on a Continuously Expanding Surface Inhibits Dedifferentiation

“…48,49 However, in the absence of CE, chondrocytes grown on silicone rubber dedifferentiated similarly to SD culture; the only differential effect of silicone rubber was an initial reduction in proliferation, which is consistent with previous studies. [50][51][52] Previous studies have also indicated an initial reduction in MSC proliferation on HESR, 17 which was subsequently overcome in prolonged CE culture. These findings, therefore, indicate that culture on a silicone surface does not by itself significantly alter a chondrocyte phenotype compared with the effects of SD culture.…”